Publications by authors named "Thorsten Derlin"

150 Publications

Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy.

Diagnostics (Basel) 2021 Mar 12;11(3). Epub 2021 Mar 12.

Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany.

Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., C-reactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [Ga]Ga-DOTA-TATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP ( < 0.001), ANC ( = 0.002), and PCM ( < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP ( = 0.0157) and NLR ( = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEP-NETs receiving PRRT.
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http://dx.doi.org/10.3390/diagnostics11030504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000284PMC
March 2021

Assessment of γ-H2AX and 53BP1 Foci in Peripheral Blood Lymphocytes to Predict Subclinical Hematotoxicity and Response in Somatostatin Receptor-Targeted Radionuclide Therapy for Advanced Gastroenteropancreatic Neuroendocrine Tumors.

Cancers (Basel) 2021 Mar 25;13(7). Epub 2021 Mar 25.

Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany.

Background: We aimed to characterize γ-H2AX and 53BP1 foci formation in patients receiving somatostatin receptor-targeted radioligand therapy, and explored its role for predicting treatment-related hematotoxicity, and treatment response.

Methods: A prospective analysis of double-strand break (DSB) markers was performed in 21 patients with advanced gastroenteropancreatic neuroendocrine tumors. γ-H2AX and 53BP1 foci formation were evaluated in peripheral blood lymphocytes (PBLs) at baseline, +1 h and +24 h after administration of 7.4 GBq (Lu)Lu-DOTA-TATE. Hematotoxicity was evaluated using standard hematology. Therapy response was assessed using (Ga)Ga-DOTA-TATE PET/CT before enrollment and after 2 cycles of PRRT according to the volumetric modification of RECIST 1.1.

Results: DSB marker kinetics were heterogeneous among patients. Subclinical hematotoxicity was associated with γ-H2AX and 53BP1 foci formation (e.g., change in platelet count vs change in γ-H2AX cells between baseline and +1 h ( = -0.6080; = 0.0045). Patients showing early development of new metastases had less γ-H2AX ( = 0.0125) and less 53BP1 foci per cell at +1 h ( = 0.0289), and demonstrated a distinct kinetic pattern with an absence of DSB marker decrease at +24 h (γ-H2AX: = 0.0025; 53BP1: = 0.0008).

Conclusions: Assessment of γ-H2AX and 53BP1 foci formation in PBLs of patients receiving radioligand therapy may hold promise for predicting subclinical hematotoxicity and early treatment response.
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http://dx.doi.org/10.3390/cancers13071516DOI Listing
March 2021

Deepening of response to prostate-specific membrane antigen ligand-targeted radioligand therapy beyond end of treatment.

Eur J Nucl Med Mol Imaging 2021 Apr 2. Epub 2021 Apr 2.

Department of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

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http://dx.doi.org/10.1007/s00259-021-05335-xDOI Listing
April 2021

Structural alteration of lung parenchyma in patients with NF1: a phenotyping study using multidetector computed tomography (MDCT).

Orphanet J Rare Dis 2021 Jan 14;16(1):29. Epub 2021 Jan 14.

Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Diffuse interstitial lung disease have been described in Neurofibromatosis type 1 (NF1), but its diversity and prevalence remain unknown. The aim of this study was to assess the prevalence and characteristics of (NF1)-associated lung manifestations in a large single-center study using multidetector computed tomography (MDCT) and to evaluate the smoking history, patients' age, genetics, and the presence of malignant peripheral nerve sheath tumors (MPNST) as potential influencing factors for lung pathologies.

Methods: In this retrospective study, 71 patients with NF1 were evaluated for the presence of distinctive lung manifestations like reticulations, consolidations, type of emphysema, pulmonary nodules and cysts. All patients underwent F-18-FDG PET/CT scans, which were reviewed by two experienced radiologists in consensus. Patients' subgroups were formed based on their smoking history (current smokers/previous smokers/never smokers), age (< 12 years, 12-18 years, > 18 years), and presence of MPNST (MPNST/no MPNST). In 57 patients (80%), genetic analysis of sequences coding for the neurofibromin on chromosome 17 was performed, which was correlated with different lung pathologies.

Results: Among all NF1 patients (33 ± 14 years, 56% females), 17 patients (24%) were current smokers and 62 patients (87%) were > 18 years old. Pulmonary cysts, nodules, and paraseptal emphysema were the most common pulmonary findings (35%, 32%, 30%). The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking. Cysts were observed only in adults, whereas no significant correlation between age and all other pulmonary findings was found (p > 0.05). Presence of MPNST was accompanied by higher rates of intrapulmonary nodules and pulmonary metastasis. Neither the presence nor absence of any of the specific gene mutations was associated with any particular lung pathology (p > 0.05).

Conclusions: All pulmonary findings in NF1 patients occurred independently from specific mutation subtypes, suggesting that many NF1 mutations can cause various pulmonary pathologies. The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking, indicating the value of smoking secession or the advice not to start smoking in NF1 patients as preventive strategy for clinicians. For screening of pulmonary manifestations in NF1 patients, an MDCT besides medical history and physical examination is mandatory in clinical routine.
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http://dx.doi.org/10.1186/s13023-021-01672-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809820PMC
January 2021

Application of MR diffusion imaging for non-invasive assessment of acute kidney injury after lung transplantation.

Medicine (Baltimore) 2020 Dec;99(49):e22445

Department of Nephrology.

To assess whether MR diffusion imaging may be applied for non-invasive detection of renal changes correlating with clinical diagnosis of acute kidney injury (AKI) in patients after lung transplantation (lutx).Fifty-four patients (mean age 49.6, range 26-64 years) after lutx were enrolled in a prospective clinical study and underwent functional MR imaging of the kidneys in the early postoperative period. Baseline s-creatinine ranged from 39 to 112 μmol/L. For comparison, 14 healthy volunteers (mean age 42.1, range 24-59 years) underwent magnetic resonance imaging (MRI) using the same protocol. Renal tissue injury was evaluated using quantification of diffusion and diffusion anisotropy with diffusion-weighted (DWI) and diffusion-tensor imaging (DTI). Renal function was monitored and AKI was defined according to Acute-Kidney-Injury-Network criteria. Statistical analysis comprised one-way ANOVA and Pearson correlation.67% of lutx patients (36/54) developed AKI, 47% (17/36) had AKI stage 1, 42% (15/36) AKI stage 2, and 8% (3/36) severe AKI stage 3. Renal apparent diffusion coefficients (ADCs) were reduced in patients with AKI, but preserved in transplant patients without AKI and healthy volunteers (2.07 ± 0.02 vs 2.18 ± 0.05 vs 2.21 ± 0.03 × 10 mm/s, P < .05). Diffusion anisotropy was reduced in all lutx recipients compared with healthy volunteers (AKI: 0.27 ± 0.01 vs no AKI: 0.28 ± 0.01 vs healthy: 0.33 ± 0.02; P < .01). Reduction of renal ADC correlated significantly with acute loss of renal function after lutx (decrease of renal function in the postoperative period and glomerular filtration rate on the day of MRI).MR diffusion imaging enables non-invasive assessment of renal changes correlating with AKI early after lutx. Reduction of diffusion anisotropy was present in all patients after lutx, whereas marked reduction of renal ADC was observed only in the group of lutx recipients with AKI and correlated with renal function impairment.
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http://dx.doi.org/10.1097/MD.0000000000022445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717793PMC
December 2020

F-FDG PET/CT of off-target lymphoid organs in CD19-targeting chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma.

Ann Nucl Med 2021 Jan 11;35(1):132-138. Epub 2020 Nov 11.

Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation, Hannover, Germany.

Objective: The interplay between systemic inflammation, activity of lymphoid organs and lymphoma activity in CD19-targeting chimeric antigen receptor (CAR)-T-cell immunotherapy, and its significance for response and toxicity, is not well defined.

Methods: Using serial F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), metabolic parameters of lymphoma and lymphoid organs were analyzed in ten patients receiving Tisagenlecleucel (an autologous CD19 CAR-T cell product) for relapsed or refractory diffuse large B-cell lymphoma. The prevalence and severity of toxicity (e.g., neurotoxicity) were noted.

Results: Achieving remission required early metabolic response (P = 0.0476). Early suppression of metabolic activity of lymphoid organs (spleen, P = 0.0368; lymph nodes, P = 0.0470) was associated with poor outcome. Lymphoma metabolic activity was significantly higher in patients with neurotoxicity (P = 0.0489).

Conclusions: Early metabolic changes in lymphoma lesions and off-target lymphoid organs parallel medium-term response to CAR-T-cell therapy. PET can identify patients at risk for severe toxicity.
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http://dx.doi.org/10.1007/s12149-020-01544-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796875PMC
January 2021

Intraprostatic Tumour Segmentation on PSMA-PET Images in Patients with Primary Prostate Cancer with a Convolutional Neural Network.

J Nucl Med 2020 Oct 30. Epub 2020 Oct 30.

Department of Radiation Oncology - Medical Center University of Freiburg, Germany.

Accurate delineation of the intraprostatic gross tumour volume (GTV) is a prerequisite for treatment approaches in patients with primary prostate cancer (PCa). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) may outperform MRI in GTV detection. However, visual GTV delineation underlies interobserver heterogeneity and is time consuming. The aim of this study was to develop a convolutional neural network (CNN) for automated segmentation of intraprostatic tumour (GTV-CNN) in PSMA-PET. The CNN (3D U-Net) was trained on Ga-PSMA-PET images of 152 patients from two different institutions and the training labels were generated manually using a validated technique. The CNN was tested on two independent internal (cohort 1: Ga-PSMA-PET, = 18 and cohort 2: F-PSMA-PET, = 19) and one external (cohort 3: Ga-PSMA-PET, = 20) test-datasets. Accordance between manual contours and GTV-CNN was assessed with Dice-Sørensen coefficient (DSC). Sensitivity and specificity were calculated for the two internal test-datasets (cohort 1: = 18, cohort 2: = 11) by using whole-mount histology. Median DSCs for cohorts 1-3 were 0.84 (range: 0.32-0.95), 0.81 (range: 0.28-0.93) and 0.83 (range: 0.32-0.93), respectively. Sensitivities and specificities for GTV-CNN were comparable with manual expert contours: 0.98 and 0.76 (cohort 1) and 1 and 0.57 (cohort 2), respectively. Computation time was around 6 seconds for a standard dataset. The application of a CNN for automated contouring of intraprostatic GTV in Ga-PSMA- and F-PSMA-PET images resulted in a high concordance with expert contours and in high sensitivities and specificities in comparison with histology reference. This robust, accurate and fast technique may be implemented for treatment concepts in primary PCa. The trained model and the study's source code are available in an open source repository.
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http://dx.doi.org/10.2967/jnumed.120.254623DOI Listing
October 2020

Molecular imaging-guided repair after acute myocardial infarction by targeting the chemokine receptor CXCR4.

Eur Heart J 2020 10;41(37):3564-3575

Department of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

Aims: Balance between inflammatory and reparative leucocytes allows optimal healing after myocardial infarction (MI). Interindividual heterogeneity evokes variable functional outcome complicating targeted therapy. We aimed to characterize infarct chemokine CXC-motif receptor 4 (CXCR4) expression using positron emission tomography (PET) and establish its relationship to cardiac outcome. We tested whether image-guided early CXCR4 directed therapy attenuates chronic dysfunction.

Methods And Results: Mice (n = 180) underwent coronary ligation or sham surgery and serial PET imaging over 7 days. Infarct CXCR4 content was elevated over 3 days after MI compared with sham (%ID/g, Day 1:1.1 ± 0.2; Day 3:0.9 ± 0.2 vs. 0.6 ± 0.1, P < 0.001), confirmed by flow cytometry and histopathology. Mice that died of left ventricle (LV) rupture exhibited persistent inflammation at 3 days compared with survivors (1.2 ± 0.3 vs. 0.9 ± 0.2% ID/g, P < 0.001). Cardiac magnetic resonance measured cardiac function. Higher CXCR4 signal at 1 and 3 days independently predicted worse functional outcome at 6 weeks (rpartial = -0.4, P = 0.04). Mice were treated with CXCR4 blocker AMD3100 following the imaging timecourse. On-peak CXCR4 blockade at 3 days lowered LV rupture incidence vs. untreated MI (8% vs. 25%), and improved contractile function at 6 weeks (+24%, P = 0.01). Off-peak CXCR4 blockade at 7 days did not improve outcome. Flow cytometry analysis revealed lower LV neutrophil and Ly6Chigh monocyte content after on-peak treatment. Patients (n = 50) early after MI underwent CXCR4 PET imaging and functional assessment. Infarct CXCR4 expression in acute MI patients correlated with contractile function at time of PET and on follow-up.

Conclusion: Positron emission tomography imaging identifies early CXCR4 up-regulation which predicts acute rupture and chronic contractile dysfunction. Imaging-guided CXCR4 inhibition accelerates inflammatory resolution and improves outcome. This supports a molecular imaging-based theranostic approach to guide therapy after MI.
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http://dx.doi.org/10.1093/eurheartj/ehaa598DOI Listing
October 2020

High Interobserver Agreement for the Standardized Reporting System SSTR-RADS 1.0 on Somatostatin Receptor PET/CT.

J Nucl Med 2021 Apr 28;62(4):514-520. Epub 2020 Aug 28.

Nuclear Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.

Recently, a standardized framework system for interpreting somatostatin receptor (SSTR)-targeted PET/CT, termed the SSTR reporting and data system (RADS) 1.0, was introduced, providing reliable standards and criteria for SSTR-targeted imaging. We determined the interobserver reliability of SSTR-RADS for interpretation of Ga-DOTATOC PET/CT scans in a multicentric, randomized setting. A set of 51 randomized Ga-DOTATOC PET/CT scans was independently assessed by 4 masked readers with different levels of experience (2 experienced readers and 2 inexperienced readers) trained on the SSTR-RADS 1.0 criteria (based on a 5-point scale from 1 [definitively benign] to 5 [high certainty that neuroendocrine neoplasia is present]). For each scan, SSTR-RADS scores were assigned to a maximum of 5 target lesions (TLs). An overall scan impression based on SSTR-RADS was indicated, and interobserver agreement rates on a TL-based, on an organ-based, and on an overall SSTR-RADS score-based level were computed. The readers were also asked to decide whether peptide receptor radionuclide therapy (PRRT) should be considered on the basis of the assigned RADS scores. Among the selected TLs, 153 were chosen by at least 2 readers (all 4 readers selected the same TLs in 58 of 153 [37.9%] instances). The interobserver agreement for SSTR-RADS scoring among identical TLs was good (intraclass correlation coefficient [ICC] ≥ 0.73 for 4, 3, and 2 identical TLs). For lymph node and liver lesions, excellent interobserver agreement rates were derived (ICC, 0.91 and 0.77, respectively). Moreover, the interobserver agreement for an overall scan impression based on SSTR-RADS was excellent (ICC, 0.88). The SSTR-RADS-based decision to use PRRT also demonstrated excellent agreement, with an ICC of 0.80. No significant differences between experienced and inexperienced readers for an overall scan impression and TL-based SSTR-RADS scoring were observed ( ≥ 0.18), thereby suggesting that SSTR-RADS seems to be readily applicable even for less experienced readers. SSTR-RADS-guided assessment demonstrated a high concordance rate, even among readers with different levels of experience, supporting the adoption of SSTR-RADS for trials, clinical routine, or outcome studies.
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http://dx.doi.org/10.2967/jnumed.120.245464DOI Listing
April 2021

Clinical Molecular Imaging of Pulmonary CXCR4 Expression to Predict Outcome of Pirfenidone Treatment in Idiopathic Pulmonary Fibrosis.

Chest 2021 Mar 19;159(3):1094-1106. Epub 2020 Aug 19.

Department of Pulmonology, Hannover Medical School, Hannover, Germany; Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany; DZL-BREATH, Hannover, Germany. Electronic address:

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease for which two antifibrotic drugs recently were approved. However, an unmet need exists to predict responses to antifibrotic treatment, such as pirfenidone. Recent data suggest that upregulated expression of CXCR4 is indicative of outcomes in IPF.

Research Question: Can quantitative, molecular imaging of pulmonary CXCR4 expression as a biomarker for disease activity predict response to the targeted treatment pirfenidone and prognosis in patients with IPF?

Study Design And Methods: CXCR4 expression was analyzed by immunohistochemistry examination of lung tissues and reverse-transcriptase polymerase chain reaction analysis of BAL. PET-CT scanning with the specific CXCR4 ligand Ga-pentixafor was performed in 28 IPF patients and compared with baseline clinical characteristics. In 16 patients, a follow-up scan was obtained 6 to 12 weeks after initiation of treatment with pirfenidone. Patients were followed up in our outpatient clinic for ≥ 12 months.

Results: Immunohistochemistry analysis showed high CXCR4 staining of epithelial cells and macrophages in areas with vast fibrotic remodeling. Targeted PET scanning revealed CXCR4 upregulation in fibrotic areas of the lungs, particularly in zones with subpleural honeycombing. Baseline CXCR4 signal demonstrated a significant correlation with Gender Age Physiology stage (r = 0.44; P = .02) and with high-resolution CT scan score (r = 0.38; P = .04). Early changes in CXCR4 signal after initiation of pirfenidone treatment correlated with the long-term course of FVC after 12 months (r = -0.75; P = .0008). Moreover, patients with a high pulmonary CXCR4 signal on follow-up PET scan after 6 weeks into treatment demonstrated a statistically significant worse outcome at 12 months (P = .002). In multiple regression analysis, pulmonary CXCR4 signal on follow-up PET scan emerged as the only independent predictor of long-term outcome (P = .0226).

Interpretation: CXCR4-targeted PET imaging identified disease activity and predicted outcome of IPF patients treated with pirfenidone. It may serve as a future biomarker for personalized guidance of antifibrotic treatment.
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http://dx.doi.org/10.1016/j.chest.2020.08.2043DOI Listing
March 2021

Gallbladder Visualization in Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE: A Potential Mimicker of Hepatic Metastases.

Clin Nucl Med 2020 Dec;45(12):e521-e522

From the Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

Gallbladder visualization represents a rare incidental finding when using somatostatin receptor-targeted SPECT radiopharmaceuticals such as In-octreotide. We present the case of a 30-year-old man with pseudomyogenic hemangioendothelioma who underwent Ga-DOTATATE PET/CT for restaging of metastatic disease and subsequent treatment with peptide receptor radionuclide therapy with Lu-DOTATATE. Posttherapeutic SPECT/CT, but not pretherapeutic or posttherapeutic PET/CT, showed gallbladder visualization, evidencing Lu-DOTATATE excretion into the bile. This case highlights that biliary Lu-DOTATATE excretion may represent a rare mimicker of hepatic metastases and emphasizes the role SPECT/CT for precise anatomical correlation to avoid misinterpretation.
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http://dx.doi.org/10.1097/RLU.0000000000003192DOI Listing
December 2020

Personalized prediction of mode of cardiac death in heart failure using supervised machine learning in the context of cardiac innervation imaging.

J Nucl Cardiol 2020 Jun 17. Epub 2020 Jun 17.

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

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http://dx.doi.org/10.1007/s12350-020-02215-zDOI Listing
June 2020

[Structured reporting in oncologic hybrid imaging: a consensus recommendation].

Nuklearmedizin 2020 Aug 16;59(4):288-293. Epub 2020 Jun 16.

Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany.

Since the clinical introduction of PET/CT in the year of 2001 and PET/MRI in the year of 2010, hybrid imaging-guided precision medicine has become an important component of diagnostic algorithms in oncology. The written report represents the primary mode of communication between the referring physician and both the nuclear medicine physician and the radiologist. Reports have considerable impact on patient management and patient outcome, and serve as a legal documentation of the services provided and the expert impression of the interpreting physician. A high-quality hybrid imaging study should result in a likewise high-quality, structured written report which satisfactorily answers the clinical question of the referring physician. In this manuscript, consensus recommendations for structure and content of oncologic hybrid imaging reports and conclusive impressions are provided. Moreover, exemplary structured reports are provided. The recommendations for structured reporting provided in this document should foster further standardization and harmonization of oncologic reports in the context of hybrid imaging. They should also simplify communication with referring physicians and support both acceptance and appreciation of the clinical value of oncologic hybrid imaging. CITATION FORMAT: · Derlin T, Gatidis S, Krause BJ et al. Konsensusempfehlung zur strukturierten Befunderstellung onkologischer PET-Hybridbildgebung. Nuklearmedizin 2020; 59: DOI:10.1055/a-1176-0275.
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http://dx.doi.org/10.1055/a-1176-0275DOI Listing
August 2020

Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy.

Strahlenther Onkol 2020 Nov 12;196(11):1006-1017. Epub 2020 May 12.

Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT).

Patients And Methods: Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2.

Results: The median follow-up duration was 39.5 months (18-60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2-3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07-3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12-12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07-154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2-3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9-19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3-17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9-8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1-41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8-13.47) of needing ADT at the last follow-up visit.

Conclusion: If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.
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http://dx.doi.org/10.1007/s00066-020-01629-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581615PMC
November 2020

Emerging molecular targets for imaging of atherosclerotic plaque using positron emission tomography.

Curr Radiopharm 2020 May 4. Epub 2020 May 4.

Department of Nuclear Medicine, Hannover Medical School, Hannover. Germany.

Background: Positron-emission-tomography (PET) using the radiopharmaceutical 18F-fluorodeoxyglucose (FDG) has become an established and validated molecular imaging modality for characterization of the inflammatory activity of atherosclerotic plaque. In the latest years, new innovative radiopharmaceuticals and applications have emerged, providing specific information on atherosclerotic plaque biology, particularly focused on inflammatory processes.

Objective: To review and highlight recent evidence on the role of PET for atherosclerosis imaging using emerging radiotracers.

Methods: A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the usefulness of nuclear hybrid imaging in atherosclerosis imaging using 18F-sodium fluoride PET, CXCR4-targeted PET, and amyloid-β-targeted PET.

Results: Atherosclerosis imaging with PET using emerging, specific tracers holds promise in improving our understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. There is increasing, high-quality evidence on the usefulness of 18F-sodium fluoride PET and - to a lesser extent - CXCR4-targeted PET, whereas amyloid-β-targeted PET is still in its infancy.

Conclusion: 18F-sodium fluoride PET, CXCR4-targeted PET and amyloid-β-targeted PET may be used to obtain molecular information on different aspects of plaque biology. Further work is required to improve technical aspects of these imaging techniques and to elucidate their ability to predict adverse cardiac events prospectively.
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http://dx.doi.org/10.2174/1874471013666200505102353DOI Listing
May 2020

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy.

BMC Cancer 2020 Apr 29;20(1):362. Epub 2020 Apr 29.

Department of Radiotherapy and Special Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, 30629, Hannover, Germany.

Background: A substantial number of patients will develop further biochemical progression after radical prostatectomy (RP) and salvage radiotherapy (sRT). Recently published data using prostate-specific membrane antigen ligand positron emission tomography (PSMA - PET) for re-staging suggest that those recurrences are often located outside the prostate fossa and most of the patients have a limited number of metastases, making them amenable to metastasis-directed treatment (MDT).

Methods: We analyzed 78 patients with biochemical progression after RP and sRT from a retrospective European multicenter database and assessed the biochemical recurrence-free survival (bRFS; PSA < nadir + 0.2 ng/ml or no PSA decline) as well as the androgen deprivation therapy- free survival (ADT-FS) using Kaplan-Meier curves. Log-rank test and multivariate analysis was performed to determine influencing factors.

Results: A total of 185 PSMA - PET positive metastases were detected and all lesions were treated with radiotherapy (RT). Concurrent ADT was prescribed in 16.7% (13/78) of patients. The median PSA level before RT was 1.90 ng/mL (range, 0.1-22.1) and decreased statistically significantly to a median PSA nadir level of 0.26 ng/mL (range, 0.0-12.25; p < 0.001). The median PSA level of 0.88 ng/mL (range, 0.0-25.8) at the last follow-up was also statistically significantly lower (p = 0.008) than the median PSA level of 1.9 ng/mL (range, 0.1-22.1) before RT. The median bRFS was 17.0 months (95% CI, 14.2-19.8). After 12 months, 55.3% of patients were free of biochemical progression. Multivariate analyses showed that concurrent ADT was the most important independent factor for bRFS (p = 0.01). The median ADT-FS was not reached and exploratory statistical analyses estimated a median ADT-FS of 34.0 months (95% CI, 16.3-51.7). Multivariate analyses revealed no significant parameters for ADT-FS.

Conclusions: RT as MDT based on PSMA - PET of all metastases of recurrent prostate cancer after RP and sRT represents a viable treatment option for well-informed and well-selected patients.
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http://dx.doi.org/10.1186/s12885-020-06883-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191762PMC
April 2020

The effect of pregnancy on growth-dynamics of neurofibromas in Neurofibromatosis type 1.

PLoS One 2020 28;15(4):e0232031. Epub 2020 Apr 28.

Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: Patients with Neurofibromatosis type 1 (NF1) develop plexiform neurofibromas (PNF) and cutaneous neurofibromas. These tumors are a major cause of the patient's morbidity and mortality. An influence of estrogen and progesterone on tumor growth has been suggested but reports on growth or malignant transformation of tumors during pregnancy remain anecdotal. The purpose of this study was to quantify growth of cutaneous and plexiform neurofibromas in NF1 patients during pregnancy, and to assess the onset of NF1 related symptoms.

Material And Methods: Retrospectively, 13 mothers with NF1 were included and compared to nullipara, nulligravida, age-matched women with NF1. All women received whole-body magnetic resonance imaging (MRI) before and after pregnancy or after a matched time period. Presence of plexiform and cutaneous neurofibromas was evaluated. PNF were subjected to semi-automated volumetry (MedX). The sum of the longest diameters (SLD) of representative cutaneous neurofibromas was determined for both groups. Clinical symptoms and subjective tumor growth were assessed.

Results: PNF were identified in 12/26 women (46.2%). Follow up showed neither new PNF nor a significant difference in growth rate (median tumor-growth/year: pregnant group-0.38% (IQR -1.1-5.4%) vs control group 3.59% (IQR -2.1-5.5%; P = 0.69). Malignant transformation of PNF was not observed. There was a significant growth of cutaneous neurofibromas in both groups (median SLD increase: pregnant group 17mm; P = 0.0026 / control group 12mm; P = 0.0004) The difference in increase of SLD was not significant (P = 0.48). Singular cutaneous neurofibromas in the pregnant group displayed high levels of tumor growth (>20%/year). NF1-associated symptoms and subjective tumor growth were not significantly increased in pregnant patients.

Conclusions: Growth of plexiform and cutaneous neurofibromas in pregnant patients is not significantly different compared to non-pregnant patients. Cutaneous neurofibromas show a significant increase in growth over time in both, pregnant and non-pregnant patients and NF1 related clinical symptoms do not significantly aggravate during the course of pregnancy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232031PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188260PMC
July 2020

Comparison of MRI and VQ-SPECT as a Screening Test for Patients With Suspected CTEPH: CHANGE-MRI Study Design and Rationale.

Front Cardiovasc Med 2020 9;7:51. Epub 2020 Apr 9.

Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hanover, Germany.

The diagnostic strategy for chronic thromboembolic pulmonary hypertension (CTEPH) is composed of two components required for a diagnosis of CTEPH: the presence of chronic pulmonary embolism and an elevated pulmonary artery pressure. The current guidelines require that ventilation-perfusion single-photon emission computed tomography (VQ-SPECT) is used for the first step diagnosis of chronic pulmonary embolism. However, VQ-SPECT exposes patients to ionizing radiation in a radiation sensitive population. The prospective, multicenter, comparative phase III diagnostic trial TEP diosis urope - MRI (CHANGE-MRI, ClinicalTrials.gov identifier ) aims to demonstrate whether functional lung MRI can serve as an equal rights alternative to VQ-SPECT in a diagnostic strategy for patients with suspected CTEPH. Positive findings are verified with catheter pulmonary angiography or computed tomography pulmonary angiography (gold standard). For comparing the imaging methods, a co-primary endpoint is used. (i) the proportion of patients with positive MRI in the group of patients who have a positive SPECT and gold standard diagnosis for chronic pulmonary embolism and (ii) the proportion of patients with positive MRI in the group of patients with negative SPECT and gold standard. The CHANGE-MRI trial will also investigate the performance of functional lung MRI without i.v. contrast agent as an index test and identify cardiac, hemodynamic, and pulmonary MRI-derived parameters to estimate pulmonary artery pressures and predict 6-12 month survival. Ultimately, this study will provide the necessary evidence for the discussion about changes in the recommendations on the diagnostic approach to CTEPH.
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http://dx.doi.org/10.3389/fcvm.2020.00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161347PMC
April 2020

Volumetric 68Ga-DOTA-TATE PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with metastatic gastroenteropancreatic neuroendocrine tumors.

Q J Nucl Med Mol Imaging 2020 Apr 14. Epub 2020 Apr 14.

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany -

Background: A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic neuroendocrine tumors, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated volumetric parameters for quantification of whole-body tumor burden from somatostatin receptor (SSR)- targeted PET/CT.

Methods: 32 patients with metastastic grade1/grade 2 gastroenteropancreatic neuroendocrine tumors who underwent a 68Ga-DOTA-TATE PET/CT for staging of disease before initiation of peptide receptor radionuclide therapy were included in this retrospective cohort analysis. Volumetric parameters of tumor lesions, SSR-derived tumor volume (SSR-TV) and total lesion SSR (TL-SSR), were calculated for each patient using a computerized volumetric technique with a 40% SUVmax cut-off, and compared with serum chromogranin A (CgA) levels. Progression-free survival (PFS) was determined in relation to volumetric parameters. In a subgroup of 18 patients, the feasibility of volumetric parameters for treatment monitoring was evaluated.

Results: Mean SSR-TV was 178±214 cm3 (range, 9-797 cm3), whereas mean TL-SSR was 4096±5191 cm3 (range, 61-19203 cm3). Baseline CgA levels were associated with whole- body tumor burden (SSR-TV, r=0.57, P=0.0008; and TL-SSR, r=0.43, P=0.01, respectively). PFS was shorter in patients with high SSR-TV and high TL-SSR (HR 5.16 (95% CI, 1.61- 29.67), P=0.009), and SSR-TV (P = 0.0067) and TL-SSR (P = 0.0215) emerged as the sole predictors of progression in regression analysis. Changes in CgA did not correctly identify treatment response (P=0.25).

Conclusions: SSR-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, and may hold potential as a clear-cut measure for assessment of treatment response.
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http://dx.doi.org/10.23736/S1824-4785.20.03238-0DOI Listing
April 2020

Influence of short-term dexamethasone on the efficacy of Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.

Prostate 2020 05 18;80(8):619-631. Epub 2020 Mar 18.

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

Background And Aim: Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration-resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with Lu-prostate-specific membrane antigen (PSMA)-617.

Patients And Methods: Seventy-one patients with mCRPC were treated with 1 to 5 cycles of Lu-PSMA-617 (6.0-7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression-free survival (PFS) were analyzed after one, three, and five cycles of RLT.

Results: PSA response rates were not significantly different between patients receiving Lu-PSMA-617 plus dexamethasone and those receiving Lu-PSMA-617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (-21% ± 50% vs +11% ± 90%, P = .08; -21% ± 69% vs +22% ± 116%, P = .07; -13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving Lu-PSMA-617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47-1.61]; P = .20). Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases.

Conclusions: We observed high response rates to Lu-PSMA-617 RLT in men with mCRPC. The short-term addition of dexamethasone to Lu-PSMA-617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.
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http://dx.doi.org/10.1002/pros.23974DOI Listing
May 2020

Prognostic risk classification for biochemical relapse-free survival in patients with oligorecurrent prostate cancer after [Ga]PSMA-PET-guided metastasis-directed therapy.

Eur J Nucl Med Mol Imaging 2020 09 16;47(10):2328-2338. Epub 2020 Mar 16.

Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Ismaninger Strasse 22, 81675, Munich, Germany.

Purpose: Since the success of prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging for patients with oligorecurrent prostate cancer (ORPC), it is increasingly used for radiotherapy as metastasis-directed therapy (MDT). Therefore, we developed a prognostic risk classification for biochemical relapse-free survival (bRFS) for patients after PSMA-PET-guided MDT after radical prostatectomy.

Methods: We analyzed 292 patients with local recurrence (LR) and/or pelvic lymph node (LN) lesions and/or up to five distant LN, bone (BM), or visceral metastases (VM) detected with [Ga]PSMA-PET imaging. Median follow-up was 16 months (range 0-57). The primary endpoint was bRFS after MDT. Cox regression analysis for risk factors was incorporated into a recursive partitioning analysis (RPA) with classification and regression tree method.

Results: PSA at recurrence ≥ 0.8 ng/mL, BM, and VM was significantly associated with biochemical relapse. RPA showed five groups with tenfold cross-validation of 0.294 (SE 0.032). After building risk classes I to IV (p < 0.0001), mean bRFS was 36.3 months (95% CI 32.4-40.1) in class I (PSA < 0.8 ng/mL, no BM) and 25.8 months (95% CI 22.5-29.1) in class II (PSA ≥ 0.8 ng/mL, no BM, no VM). LR and/or pelvic LNs caused relapse in classes I and II. Mean bRFS was 16.0 months (95% CI 12.4-19.6) in class III (PSA irrelevant, present BM) and 5.7 months (95% CI 2.7-8.7) in class IV (PSA ≥ 0.8 ng/mL, no BM, present VM).

Conclusion: We developed and internally validated a risk classification for bRFS after PSMA-PET-guided MDT. Patients with PSA < 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) had the most promising bRFS. PSA ≥ 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) indicated intermediate risk for failure. Patients with BM were at higher risk regardless of the PSA. However, those patients still show satisfactory bRFS. In patients with VM, bRFS is heavily decreased. MDT in such cases should be discussed individually.
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http://dx.doi.org/10.1007/s00259-020-04760-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396407PMC
September 2020

Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: A Single-Center Retrospective Study.

J Nucl Med 2020 11 13;61(11):1602-1606. Epub 2020 Mar 13.

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer. We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing Lu-PSMA-617 RLT. The primary endpoint was a prostate-specific antigen response in relation to baseline neuroendocrine marker profiles. An additional endpoint was progression-free survival. Tumor uptake on posttherapeutic scans, a known predictive marker for response, was used as a control variable. Neuroendocrine biomarker profiles were abnormal in most patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression ( ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response ( = 0.0030) and reduced risk of early progression ( = 0.0111). Neuroendocrine marker profiles do not predict an adverse outcome from RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving a tumor response.
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http://dx.doi.org/10.2967/jnumed.120.241588DOI Listing
November 2020

[Theranostics and hybrid imaging for somatostatin receptor-expressing tumors].

Radiologe 2020 May;60(5):413-420

Klinik für Nuklearmedizin, Medizinische Hochschule Hannover (MHH), OE 8250, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.

Clinical/methodical Issue: Conventional imaging tests like computed tomography (CT) cannot visualize somatostatin receptor (SSTR) expression on the tumor cell surface.

Standard Radiological Methods: For imaging of SSTR-expressing tumors conventional morphological imaging tests such as CT or magnetic resonance imaging (MRI) are employed.

Methodical Innovations: Molecular imaging of SSTR expression on the tumor cell surface, in particular by using (whole body) single photon emission computed tomography (SPECT) and positron emission tomography (PET), are considered the current standard of care. Only the use of CT enables for exact localization of putative sites of disease (hybrid imaging).

Performance: Hybrid SPECT/CT and PET/CT are of utmost importance for staging and monitoring of treatment efficacy. SSTR-PET is superior to SPECT and the PET radiotracer Ga-DOTATATE has been approved in multiple countries. In addition, SSTR positivity revealed by SPECT or PET pave the way for a peptide receptor radionuclide therapy (PRRT). Such a theranostic approach enables for systemic or locoregional radiation with β‑emitting radionuclides, which are linked to the identical amino acid peptide used for PET or SPECT imaging. The prospective, randomized Netter‑1 trial has shown significant benefit for patients receiving PRRT.

Achievements: A combined use of conventional and functional imaging tests is superior to conventional imaging alone and allows for identification of suitable candidates for a theranostic approach.

Practical Recommendations: In case of clinical suspicion or after having obtained histological evidence, hybrid SSTR-SPECT/CT or -PET/CT should be performed, preferably in a dedicated molecular imaging center.
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http://dx.doi.org/10.1007/s00117-020-00652-yDOI Listing
May 2020

F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging.

Theranostics 2020 1;10(1):1-16. Epub 2020 Jan 1.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from Ga- to F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite Ge/Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
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http://dx.doi.org/10.7150/thno.37894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929634PMC
April 2021

Validation of Automated Perfusion-Weighted Phase-Resolved Functional Lung (PREFUL)-MRI in Patients With Pulmonary Diseases.

J Magn Reson Imaging 2020 07 24;52(1):103-114. Epub 2019 Dec 24.

Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.

Background: Perfusion-weighted (Qw) noncontrast-enhanced proton lung MRI is a promising technique for assessment of pulmonary perfusion, but still requires validation.

Purpose: To improve perfusion-weighted phase-resolved functional lung (PREFUL)-MRI, to validate PREFUL with perfusion single photon emission computed tomography (SPECT) as a gold standard, and to compare PREFUL with dynamic contrast-enhanced (DCE)-MRI as a reference.

Study Type: Retrospective.

Population: Twenty patients with chronic obstructive pulmonary disease (COPD), 14 patients with cystic fibrosis (CF), and 21 patients with chronic thromboembolic pulmonary hypertension (CTEPH) were included.

Field Strength/sequence: For PREFUL-MRI, a spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories sequence were used at 1.5T.

Assessment: PREFUL-MRI coronal slices were acquired in free-breathing. DCE-MRI was performed in breath-hold with injection of 0.03 mmol/kg bodyweight of gadoteric acid at a rate of 4 cc/s. Perfusion SPECT images were obtained for six CTEPH patients. Images were coregistered. An algorithm to define the appropriate PREFUL perfusion phase was developed using perfusion SPECT data. Perfusion defect percentages (QDP) and Qw-values were calculated for all methods. For PREFUL quantitative perfusion values (PREFUL ) and for DCE pulmonary blood flow (PBF) was calculated.

Statistical Tests: Obtained parameters were assessed using Pearson correlation and Bland-Altman analysis.

Results: Qw-SPECT correlated with Qw-DCE (r = 0.50, P < 0.01) and Qw-PREFUL (r = 0.47, P < 0.01). Spatial overlap of QDP maps showed an agreement ≥67.7% comparing SPECT and DCE, ≥64.1% for SPECT and PREFUL, and ≥60.2% comparing DCE and PREFUL. Significant correlations of Qw-PREFUL and Qw-DCE were found (COPD: r = 0.79, P < 0.01; CF: r = 0.77, P < 0.01; CTEPH: r = 0.73, P < 0.01). PREFUL /PBF correlations were similar/lower (CF, CTEPH: P > 0.12; COPD: P < 0.01) compared to Qw-PREFUL/DCE correlations. PREFUL -values were higher/similar compared to PBF-values (COPD, CF: P < 0.01; CTEPH: P = 0.026).

Data Conclusion: The automated PREFUL algorithm may allow for noncontrast-enhanced pulmonary perfusion assessment in COPD, CF, and CTEPH patients comparable to DCE-MRI. Level of Evidence 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:103-114.
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http://dx.doi.org/10.1002/jmri.27027DOI Listing
July 2020

F-FDG PET/CT in Left-Ventricular Assist Device Infection: Initial Results Supporting the Usefulness of Image-Guided Therapy.

J Nucl Med 2020 07 5;61(7):971-976. Epub 2019 Dec 5.

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and

Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of F-FDG PET/CT for guidance of patient management. Fifty-seven LVAD-carrying patients received 85 whole-body F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained for up to 2 y. PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of patients), subcutaneous driveline path (87%), pump pocket (49%), and outflow tract (58%). Driveline smears revealed or strains as the underlying pathogen in most cases (48 and 34%, respectively). At receiver-operating-characteristic analysis, an F-FDG SUV of more than 2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend toward lower survival than did infection of 2 or fewer components ( = 0.089), whereas involvement of thoracic lymph nodes was significantly associated with an adverse outcome ( = 0.001 for nodal SUV above vs. below median). Finally, patients who underwent early surgical revision within 3 mo after PET/CT ( = 21) required significantly less inpatient hospital care during follow-up than did those receiving delayed surgical revision ( = 11; < 0.05). Whole-body F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course.
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http://dx.doi.org/10.2967/jnumed.119.237628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383076PMC
July 2020

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Oligorecurrent Prostate Cancer Treated with Metastases-directed Radiotherapy: Role of Addition and Duration of Androgen Deprivation.

Eur Urol Focus 2021 Mar 5;7(2):309-316. Epub 2019 Sep 5.

Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland.

Background: Approximately 40-70% of biochemically recurrent prostate cancer (PCa) is oligorecurrent after prostate-specific membrane antigen (PSMA) positron emission tomography (PET) staging. Metastasis-directed radiotherapy (MDT) of PSMA-positive oligorecurrence is now frequently used, but the role of concurrent androgen deprivation therapy (ADT) remains unclear.

Objective: To determine the effect of concurrent ADT with PSMA PET-directed MDT on biochemical progression-free survival (bRFS).

Design, Setting, And Participants: This was a retrospective multicenter study of 305 patients with biochemical recurrence and PSMA PET-positive oligorecurrence following initial curative treatment between April 2013 and January 2018.

Intervention: MDT with fractionated or stereotactic body radiotherapy for all PSMA-positive metastatic sites; 37.8% received concurrent ADT.

Outcome Measurements And Statistical Analysis: The primary outcome was bRFS, which was measured using Kaplan-Meier curves and log-rank testing. Secondary outcomes were ADT-free survival, overall survival (OS), and toxicity was analyzed using the Common Terminology Criteria for Adverse Events v4.03. Univariate and multivariate analyses were performed to determine independent clinicopathological factors.

Results And Limitations: The median follow-up was 16 mo (interquartile range 9-27). Some 96% of the patients initially had high-risk PCa. A median of one (range 0-19) nodal metastases and one (range 0-5) distant metastases were treated. MDT+ADT significantly improved bRFS and remained an independent factor (hazard ratio 0.28, 95% confidence interval 0.16-0.51; p<0.0001). bRFS was not significantly different between MDT+≤6 mo of ADT and MDT alone (p=0.121). Patients receiving MDT had 1- and 2-yr ADT-free survival of 93% and 83%, respectively. New therapies, most frequently MDT (23%), were required more frequently after MDT (85% vs 29%; p<0.001). Grade ≥3 acute toxicity was observed in 0.9% of patients and late toxicity in 2.3%.

Conclusions: In this cohort of patients with oligorecurrent PCa, concurrent ADT with MDT improved bRFS significantly, but a large number of patients treated with MDT were spared from ADT for 2yr, although a greater need for other salvage therapies was observed.

Patient Summary: The role of concurrent androgen deprivation therapy (ADT) with radiotherapy for prostate cancer oligorecurrence identified on prostate-specific membrane antigen positron emission tomography was studied. We concluded that radiotherapy alone could prolong the time to start of ADT. However, the risk of disease progression and consequently the need for further treatments is higher after local radiotherapy alone without immediate ADT.
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http://dx.doi.org/10.1016/j.euf.2019.08.012DOI Listing
March 2021

Validation of different PSMA-PET/CT-based contouring techniques for intraprostatic tumor definition using histopathology as standard of reference.

Radiother Oncol 2019 12 17;141:208-213. Epub 2019 Aug 17.

Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine. University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.

Purpose: Accurate definition of the intraprostatic gross tumor volume (GTV) is crucial for diagnostic and therapeutic approaches in patients with primary prostate cancer (PCa). The optimal methodology for contouring of GTV using Prostate specific membrane antigen positron emission tomography (PSMA-PET) information has not yet been defined.

Methods And Materials: PCa patients who underwent a [68Ga]PSMA-11-PET/CT followed by radical prostatectomy were prospectively enrolled (n = 20). Six observer teams with different levels of experience and using different PET image scaling techniques performed manual contouring of GTV. Additionally, semi-automatic segmentation of GTVs was performed using SUVmax thresholds of 20-50%. Coregistered histopathological gross tumor volume (GTV-Histo) served as reference. Inter-observer agreement was assessed by calculating the Dice similarity coefficient (DSC).

Results: Most contouring methods provided high sensitivity and specificity. For manual delineation, scaling the PET images from SUVmin-max: 0-5 resulted in high sensitivity (>86%). The highest specificity (100%) was obtained by scaling the PET images from SUVmin-max: 0-SUVmax. High interobserver agreement (median DSC 0.8) was observed when using the same PET image scaling technique (PET images SUVmin-max: 0-5). For semi-automatic segmentation, a low SUVmax threshold of 20% optimized sensitivity (SUVmax threshold 20%, 100% sensitivity, 32% of prostatic volume), whereas a higher threshold optimized specificity (SUVmax threshold 40%-50%, 100% specificity).

Conclusions: Contouring of regions with high tracer-uptake resulted in very high specificities and should be used for biopsy guidance. Both manual and semi-automatic approaches using validated SUV scaling (SUVmin-max: 0-5) or thresholding (20%) may provide high sensitivity, and should be considered for PSMA-PET-based focal therapy approaches.
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http://dx.doi.org/10.1016/j.radonc.2019.07.002DOI Listing
December 2019

Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers-Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT.

J Clin Med 2019 Jul 19;8(7). Epub 2019 Jul 19.

Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Baltimore, MD 21287, USA.

The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted imaging and therapy for the treatment of neuroendocrine tumors (NET), as well as prostate-specific membrane antigen (PSMA)-targeted imaging and therapy for the treatment of prostate cancer (PC). As such, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy using positron emission tomography (PET). While interpreting PSMA- or SSTR-targeted PET/computed tomography scans, the reader has to navigate certain pitfalls, including (I.) varying normal biodistribution between different PSMA- and SSTR-targeting PET radiotracers, (II.) varying radiotracer uptake in numerous kinds of both benign and malignant lesions, and (III.) resulting false-positive and false-negative findings. Thus, two novel reporting and data system (RADS) classifications for PSMA- and SSTR-targeted PET imaging (PSMA- and SSTR-RADS) have been recently introduced under the umbrella term molecular imaging reporting and data systems (MI-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied. Learning objectives of the present case-based review are as follows: (I.) the theranostic concept for the treatment of NET and PC will be briefly introduced, (II.) the most common pitfalls on PSMA- and SSTR-targeted PET/CT will be identified, (III.) the novel framework system for theranostic radiotracers (MI-RADS) will be explained, applied to complex clinical cases and recent studies in the field will be highlighted. Finally, current treatment strategies based on MI-RADS will be proposed, which will demonstrate how such a generalizable framework system truly paves the way for clinically meaningful molecular imaging-guided treatment of either PC or NET. Thus, beyond an introduction of MI-RADS, the present review aims to provide an update of recently published studies which have further validated the concept of structured reporting systems in the field of theranostics.
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http://dx.doi.org/10.3390/jcm8071060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678732PMC
July 2019