Publications by authors named "Rudolf A Werner"

117 Publications

[18F]DCFPyL PET/CT for Imaging of Prostate Cancer.

Nuklearmedizin 2022 Jan 14. Epub 2022 Jan 14.

Nuclear Medicine, Würzburg University Medical Center Clinic for Nuclear Medicine, Würzburg, Germany.

Prostate-specific membrane antigen (PSMA)-directed positron emission tomography (PET) has gained increasing interest for imaging of men affected by prostate cancer (PC). In recent years, Ga-labeled PSMA compounds have been widely utilized, although there is a trend towards increased utilization of F-labeled agents. Among others, [F]DCFPyL (piflufolastat F 18, PYLARIFY) has been tested in multiple major trials, such as OSPREY and CONDOR, which provided robust evidence on the clinical utility of this compound for staging, restaging, and change in management. Recent explorative prospective trials have also utilized [F]DCFPyL PET/CT for response assessment, e.g., in patients under abiraterone or enzalutamide, rendering this F-labeled PSMA radiotracer as an attractive biomarker for image-guided strategies in men with PC. After recent approval by the U.S. Food and Drug Administration, one may expect more widespread use, not only in the U.S., but also in Europe in the long term. In the present review, we will provide an overview of the current clinical utility of [F]DCFPyL in various clinical settings for men with PC.
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http://dx.doi.org/10.1055/a-1659-0010DOI Listing
January 2022

The Number of Frames on ECG-Gated F-FDG Small Animal PET Has a Significant Impact on LV Systolic and Diastolic Functional Parameters.

Mol Imaging 2021 6;2021:4629459. Epub 2021 Dec 6.

Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.

Objectives: This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats.

Methods: F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed.

Results: Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 ± 57.7 l, 380.8 ± 57.2 l, 398.0 ± 63.1 l, and 444.8 ± 75.3 l at 4, 8, 12, and 16 frames, respectively; < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed ( < 0.005), but not for 4, 8, and 12 frames.

Conclusions: Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.
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http://dx.doi.org/10.1155/2021/4629459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694669PMC
December 2021

Targeting 11-beta hydroxylase with [ 131I]IMAZA - a novel approach for the treatment of advanced adrenocortical carcinoma.

J Clin Endocrinol Metab 2021 Dec 14. Epub 2021 Dec 14.

Department of Nuclear Medicine, University Hospital, University of Würzburg, Oberdürrbacher Straße 6, D-97080 Würzburg, Germany.

Introduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment. Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[ 123I]Iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([ 123I]IMAZA) for diagnostic imaging and [ 131I]IMAZA for radionuclide therapy.

Patients And Treatment: 69 patients with non-resectable, metastatic ACC were screened, using a diagnostic [ 123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [ 131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0).

Results: After screening, 13 patients were treated with a median of 25.7 GBq [ 131I]IMAZA (range, 18.1-30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of 26% in two patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range, 8.321.9). Median overall survival in all patients was 14.1 months (4.056.5) after therapy. Treatment was well tolerated, i.e. no severe toxicities (CTCAE grade ≥3) were observed.

Conclusion: In patients with advanced ACC refractory to standard therapeutic regimens, [ 131I]IMAZA treatment was associated with disease stabilization and non-significant tumour size reduction in a significant patient fraction and only limited toxicities. High [ 131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach.
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http://dx.doi.org/10.1210/clinem/dgab895DOI Listing
December 2021

Whole-Body [F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease.

Diagnostics (Basel) 2021 Nov 9;11(11). Epub 2021 Nov 9.

Comprehensive Heart Failure Center, Department of Nuclear Medicine, University Hospital Würzburg, 97080 Würzburg, Germany.

The 2-deoxy-d-[F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [F]FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [F]FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [F]FDG PET/CT, 22/34 (64.7%) of patients did not have an established diagnosis, whereas in 7/34 (20.6%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [F]FDG PET/CT, the diagnosis was GCA in 19/34 (55.9%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5%) and PMR in the remaining 6/34 (17.6%). As such, [F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95%CI, 0.95-1.1) vs. PMR, 0.92 ± 0.1 (95%CI, 0.85-0.99), = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95%CI, 0.95-1.13), = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95%CI, 0.83-1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95%CI, 0.55-0.61)) and GCA + PMR (0.64 ± 0.09 (95%CI, 0.57-0.71); < 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases.
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http://dx.doi.org/10.3390/diagnostics11112073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625716PMC
November 2021

Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA-targeted radioligand therapy.

Prostate 2022 Jan 11;82(1):86-96. Epub 2021 Oct 11.

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

Background: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT.

Methods: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up.

Results: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007).

Conclusion: Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.
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http://dx.doi.org/10.1002/pros.24250DOI Listing
January 2022

No major impact of prescribed CAD drugs on myocardial perfusion uptake derived by []rubidium PET.

J Nucl Cardiol 2021 Oct 5. Epub 2021 Oct 5.

Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.

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http://dx.doi.org/10.1007/s12350-021-02786-5DOI Listing
October 2021

Biokinetics and Dosimetry of [Lu]Lu-Pentixather.

J Nucl Med 2021 Aug 19. Epub 2021 Aug 19.

University Hospital Würzburg, Germany.

The chemokine receptor CXCR4, which is overexpressed in many solid and hematologic malignancies, can be targeted for radiopeptide therapy via the antagonist Pentixather®. Biokinetics and dosimetry of Lu-Pentixather and Y-Pentixather were analyzed. This retrospective study is a standardized reevaluation of data collected for treatment planning. Nineteen patients with complete sets of planar whole-body scans over at least four days and a single SPECT/CT after 200 MBq Lu-Pentixather were included. Kinetics were measured in the whole body, in tissues with activity retention, and in 10 individuals in the blood. Time-integrated activity coefficients and tissue absorbed doses were derived. Increased uptake of Pentixather was observed in kidneys, liver, spleen, and bone marrow, inducing median (minimum-maximum) absorbed doses of 0.91 (0.38-3.47), 0.71 (0.39-1.17), 0.58 (0.34-2.26), and 0.47 (0.14-2.33) Gy per GBq Lu-Pentixather and 3.75 (1.48-12.2), 1.61 (1.14-2.97), 1.66 (0.97-6.69), and 1.06 (0.27-4.45) Gy per GBq Y-Pentixather, respectively. In most tissues, activity increased during the first day after the administration of Lu-Pentixather and afterwards decayed with mean effective half-lives of 41 ± 10 (range: 24-64) hours in kidneys and median half-lives of 109, 86, and 92 hours in liver, spleen, and bone marrow, respectively. Maximum uptake per kidney was 2.2% ± 1.0% (range: 0.6%-5.1%). In organs showing no specific uptake, absorbed doses exceeding 0.3 Gy per GBq Y-Pentixather are estimated for the urinary bladder and for tissues adjacent to accumulating organs such as the adrenal glands, bone surface, and gallbladder. Dose estimates for tumors and extramedullary lesions ranged from 1.5 to 18.2 Gy per GBq Y-Pentixather. In patients with hematologic neoplasms, absorbed doses calculated for bone marrow and extramedullary lesions are sufficient to be effective as an adjunct to high-dose chemotherapies prior to stem cell transplantation.
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http://dx.doi.org/10.2967/jnumed.121.262295DOI Listing
August 2021

PET Imaging for Prostate Cancer.

Radiol Clin North Am 2021 Sep;59(5):801-811

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road NE, Atlanta, GA 30322, USA.

The role of PET imaging with C-choline and F-fluciclovine in evaluating patients with prostate cancer (PCa) has become more important over the years and has been incorporated into the NCCN guidelines. A new generation of PET radiotracers targeting the prostate-specific membrane antigen (PSMA) is widely used outside the United States to evaluate patients with primary PCa and PCa recurrence. PET imaging influences treatment planning and demonstrates a significantly higher disease detection rate than conventional imaging such as computed tomography and MR imaging. Early data indicate that using PET radiotracers such as F-fluciclovine and PSMA improves patient outcomes. 68-Ga-PSMA-11 and 18F-DCFPyL-PET/CT were recently approved by the US Food & Drug Administration (FDA) for clinical use. Other PSMA radiotracers, including fluorinated variants, will likely gain FDA approval in the not-too-distant future.
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http://dx.doi.org/10.1016/j.rcl.2021.05.008DOI Listing
September 2021

Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction.

Theranostics 2021 6;11(16):7984-7994. Epub 2021 Jul 6.

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

Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup. Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome. In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27). Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.
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http://dx.doi.org/10.7150/thno.61423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315063PMC
August 2021

Narrative review of generative adversarial networks in medical and molecular imaging.

Ann Transl Med 2021 May;9(9):821

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

Recent years have witnessed a rapidly expanding use of artificial intelligence and machine learning in medical imaging. Generative adversarial networks (GANs) are techniques to synthesize images based on artificial neural networks and deep learning. In addition to the flexibility and versatility inherent in deep learning on which the GANs are based, the potential problem-solving ability of the GANs has attracted attention and is being vigorously studied in the medical and molecular imaging fields. Here this narrative review provides a comprehensive overview for GANs and discuss their usefulness in medical and molecular imaging on the following topics: (I) data augmentation to increase training data for AI-based computer-aided diagnosis as a solution for the data-hungry nature of such training sets; (II) modality conversion to complement the shortcomings of a single modality that reflects certain physical measurement principles, such as from magnetic resonance (MR) to computed tomography (CT) images or vice versa; (III) de-noising to realize less injection and/or radiation dose for nuclear medicine and CT; (IV) image reconstruction for shortening MR acquisition time while maintaining high image quality; (V) super-resolution to produce a high-resolution image from low-resolution one; (VI) domain adaptation which utilizes knowledge such as supervised labels and annotations from a source domain to the target domain with no or insufficient knowledge; and (VII) image generation with disease severity and radiogenomics. GANs are promising tools for medical and molecular imaging. The progress of model architectures and their applications should continue to be noteworthy.
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http://dx.doi.org/10.21037/atm-20-6325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246192PMC
May 2021

PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under Lu-PSMA-617 Radioligand Therapy.

Cancers (Basel) 2021 Jun 11;13(12). Epub 2021 Jun 11.

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

Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with Ga-PSMA-11 prior to two cycles of Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUV), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUV (r = -0.49; < 0.001), but not with PSMA-TV (r = 0.02; = 0.89) or TL-PSMA (r = -0.15; = 0.22). A cut-off of 19.8 for SUV and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age ( < 0.001). Multivariate analysis identified SUV (HR, 7.94, = 0.001) and age (HR, 8.05, = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.
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http://dx.doi.org/10.3390/cancers13122938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230748PMC
June 2021

Calcitonin gene-related peptide (CGRP)-induced recovery after myocardial infarction: Is there a role for CGRP-targeted molecular image-guided strategies in cardiology?

J Nucl Cardiol 2021 Jun 4. Epub 2021 Jun 4.

Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.

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http://dx.doi.org/10.1007/s12350-021-02686-8DOI Listing
June 2021

Comparison of pretherapeutic osseous tumor volume and standard hematology for prediction of hematotoxicity after PSMA-targeted radioligand therapy.

Eur J Nucl Med Mol Imaging 2021 11 27;48(12):4077-4088. Epub 2021 May 27.

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

Purpose: Hematotoxicity is a potentially dose-limiting adverse event in patients with metastasized castration-resistant prostate cancer (mCRPC) undergoing prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT). We aimed to identify clinical or PSMA-targeted imaging-derived parameters to predict hematological adverse events at early and late stages in the treatment course.

Methods: In 67 patients with mCRPC scheduled for Lu-PSMA-617 RLT, pretherapeutic osseous tumor volume (TV) from Ga-PSMA-11 PET/CT and laboratory values were assessed. We then tested the predictive capability of these parameters for early and late hematotoxicity (according to CTCAE vers. 5.0) after one cycle of RLT and in a subgroup of 32/67 (47.8%) patients after four cycles of RLT.

Results: After one cycle, 10/67 (14.9%) patients developed leukocytopenia (lymphocytopenia, 39/67 [58.2%]; thrombocytopenia, 17/67 [25.4%]). A cut-off of 5.6 × 10/mm for baseline leukocytes was defined by receiver operating characteristics (ROC) and separated between patients with and without leukocytopenia (P < 0.001). Baseline leukocyte count emerged as a stronger predictive factor in multivariate analysis (hazard ratio [HR], 33.94, P = 0.001) relative to osseous TV (HR, 14.24, P = 0.01). After four cycles, 4/32 (12.5%) developed leukocytopenia and the pretherapeutic leukocyte cut-off (HR, 9.97, P = 0.082) tended to predict leukocytopenia better than TV (HR, 8.37, P = 0.109). In addition, a cut-off of 1.33 × 10/mm for baseline lymphocytes separated between patients with and without lymphocytopenia (P < 0.001), which was corroborated in multivariate analysis (HR, 21.39, P < 0.001 vs. TV, HR, 4.57, P = 0.03). After four cycles, 19/32 (59.4%) developed lymphocytopenia and the pretherapeutic cut-off for lymphocytes (HR, 46.76, P = 0.007) also demonstrated superior predictive performance for late lymphocytopenia (TV, HR, 5.15, P = 0.167). Moreover, a cut-off of 206 × 10/mm for baseline platelets separated between patients with and without thrombocytopenia (P < 0.001) and also demonstrated superior predictive capability in multivariate analysis (HR, 115.02, P < 0.001 vs.TV, HR, 12.75, P = 0.025). After four cycles, 9/32 (28.1%) developed thrombocytopenia and the pretherapeutic cut-off for platelets (HR, 5.44, P = 0.048) was also superior for the occurrence of late thrombocytopenia (TV, HR, 1.44, P = 0.7).

Conclusions: Pretherapeutic leukocyte, lymphocyte, and platelet levels themselves are strong predictors for early and late hematotoxicity under PSMA-directed RLT, and are better suited than PET-based osseous TV for this purpose.
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http://dx.doi.org/10.1007/s00259-021-05412-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484194PMC
November 2021

[18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species.

Sci Rep 2021 05 25;11(1):10896. Epub 2021 May 25.

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n = 1), rats (n = 4), rabbits (n = 4) and non-human primates (n = 3), via carotid artery in rats (n = 4) and non-human primates (n = 3), and via intra-myocardial injection in rats (n = 5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
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http://dx.doi.org/10.1038/s41598-021-90383-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149709PMC
May 2021

Theranostics in Oncology-Thriving, Now More than Ever.

Diagnostics (Basel) 2021 Apr 29;11(5). Epub 2021 Apr 29.

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

Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by substantial prolongation of progression-free and overall survival, but are also generally safe, rendering theranostic agents as an attractive treatment option in various clinical scenarios in oncology. In this Special Issue , nine original articles from around the globe provide further evidence on the use of the theranostic concept for neuroendocrine neoplasm (NEN), prostate cancer (PC), meningioma, and neuroblastoma. The investigated diagnostic and therapeutic radiotracers target not only established structures, such as somatostatin receptor, prostate-specific membrane antigen or norepinephrine transporter, but also recently emerging targets such as the C-X-C motif chemokine receptor 4. Moreover, the presented original articles also combine the concept of theranostics with in-depth read-out techniques such as radiomics or novel reconstruction algorithms on pretherapeutic scans, e.g., for outcome prediction. Even 80 years after its initial clinical introduction, theranostics in oncology continues to thrive, now more than ever.
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http://dx.doi.org/10.3390/diagnostics11050805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146294PMC
April 2021

Effect of Point-Spread Function Reconstruction for Indeterminate PSMA-RADS-3A Lesions on PSMA-Targeted PET Imaging of Men with Prostate Cancer.

Diagnostics (Basel) 2021 Apr 7;11(4). Epub 2021 Apr 7.

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

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is emerging as an important modality for imaging patients with prostate cancer (PCa). As with any imaging modality, indeterminate findings will arise. The PSMA reporting and data system (PSMA-RADS) version 1.0 codifies indeterminate soft tissue findings with the PSMA-RADS-3A moniker. We investigated the role of point-spread function (PSF) reconstructions on categorization of PSMA-RADS-3A lesions.

Methods: This was a post hoc analysis of an institutional review board approved prospective trial. Around 60 min after the administration of 333 MBq (9 mCi) of PSMA-targeted F-DCFPyL, patients underwent PET/computed tomography (CT) acquisitions from the mid-thighs to the skull vertex. The PET data were reconstructed with and without PSF. Scans were categorized according to PSMA-RADS version 1.0, and all PSMA-RADS-3A lesions on non-PSF images were re-evaluated to determine if any could be re-categorized as PSMA-RADS-4. The maximum standardized uptake values (SUVs) of the lesions, mean SUVs of blood pool, and the ratios of those values were determined.

Results: A total of 171 PSMA-RADS-3A lesions were identified in 30 patients for whom both PSF reconstructions and cross-sectional imaging follow-up were available. A total of 13/171 (7.6%) were re-categorized as PSMA-RADS-4 lesions with PSF reconstructions. A total of 112/171 (65.5%) were found on follow-up to be true positive for PCa, with all 13 of the re-categorized lesions being true positive on follow-up. The lesions that were re-categorized trended towards having higher SUV-lesion and SUV-lesion/SUV-blood-pool metrics, although these relationships were not statistically significant.

Conclusions: The use of PSF reconstructions for F-DCFPyL PET can allow the appropriate re-categorization of a small number of indeterminate PSMA-RADS-3A soft tissue lesions as more definitive PSMA-RADS-4 lesions. The routine use of PSF reconstructions for PSMA-targeted PET may be of value at those sites that utilize this technology.
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http://dx.doi.org/10.3390/diagnostics11040665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067967PMC
April 2021

Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon.

Theranostics 2021 7;11(12):6105-6119. Epub 2021 Apr 7.

Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C, Ga, and F have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
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http://dx.doi.org/10.7150/thno.58682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058716PMC
July 2021

A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177-labeled Prostate-specific Membrane Antigen-targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

Eur Urol 2021 07 8;80(1):82-94. Epub 2021 Apr 8.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Context: Castration-resistant prostate cancer (CRPC) treatment is an evolving challenge. Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the β-particle-emitting radionuclide lutetium-177 (Lu) is a promising new approach.

Objective: In this systematic review and meta-analysis, we evaluated the efficacy and toxicity of PRLT.

Evidence Acquisition: A systematic search was performed in PubMed/Medline (last updated February 18, 2019). A total of 250 studies were reviewed, and 24 studies with 1192 patients were included in the analysis. Proportions of patients with ≥50% serum prostate-specific antigen (PSA) decrease, any PSA decrease, and any PSA increase were extracted. Proportions of patients showing any grade toxicity and those with grade 3/4 toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) grading were extracted from manuscripts. Overall survival and progression-free survival were evaluated. A meta-analysis of single proportions was carried out. Furthermore, we compared the two most common PRLT agents, Lu-PSMA with Lu-PSMA-I&T, for effectiveness and toxicity.

Evidence Synthesis: Among the 24 included studies, 20 included data on Lu-PSMA-617, three included data on Lu-PSMA-I&T, and one study had aggregated data for Lu-PSMA-617 and Lu-PSMA-I&T. The estimated proportion of Lu-PSMA-617-treated patients who showed a serum PSA decrease of ≥50% with at least an 8-wk interval between therapy and PSA measurement was 0.44 (0.39; 0.50). Therapy with Lu-PSMA-I&T demonstrated an estimated proportion of patients with ≥50% PSA reduction to be 0.36 (0.26; 0.47). The aggregate results for men treated with more than one cycle of any kind of PRLT showed an estimated proportion of 0.46 (0.41; 0.51) for PSA response ≥50%. Regarding aggregate data from all of the PRLT agents, we found that grade 3 and 4 toxicities were uncommon, with estimated proportions from 0.01 (0.00;0.04) for nausea, fatigue, diarrhea, and elevated aspartate transaminase up to 0.08 (0.05; 0.12) for anemia. There was considerable heterogeneity among the studies in the "any-grade toxicity" groups. Meta-regression showed that more than one cycle of PRLT is associated with a greater proportion of patients with ≥50% PSA reduction. Overall survival according to pooled hazard ratios (HRs) for any PSA decline was 0.29 (0.18; 0.46), and for >50% PSA reduction was 0.67 (0.43; 1.07). Progression-free survival according to a pooled HR of >50% PSA reduction was 0.53 (0.32; 0.86).

Conclusions: The relatively high number of PSA responders alongside the low rate of severe toxicity reflects the potentially promising role of PRLT in treating CRPC. The ultimate utility of this treatment modality will become clearer as multiple prospective studies continue to accrue. In the interim, this systematic review and meta-analysis can serve as a compendium of effectiveness and adverse events associated with PRLT for treating clinicians.

Patient Summary: Prostate-specific membrane antigen-targeted endoradiotherapy/radioligand therapy (PRLT) is associated with ≥50% reduction in prostate-specific antigen level in a large number of patients and a low rate of toxicity, reflecting its potential in treating castration-resistant prostate cancer. This systematic review and meta-analysis presents as a compendium of the effectiveness and adverse events related to PRLT for treating clinicians.
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http://dx.doi.org/10.1016/j.eururo.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206006PMC
July 2021

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036952PMC
March 2021

CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas.

Diagnostics (Basel) 2021 Mar 29;11(4). Epub 2021 Mar 29.

European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital Würzburg, 97080 Würzburg, Germany.

We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. Ga-Pentixafor visualized tumor lesions in 10/11 subjects, whileF-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, = 107; < 0.001). Semi-quantitative analysis revealed markedly higher F-FDG uptake as compared to Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUV: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUV: 7.4 ± 5.4 vs. 3.1 ± 3.2, < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard F-FDG PET/CT.
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http://dx.doi.org/10.3390/diagnostics11040605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067200PMC
March 2021

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

J Nucl Med 2021 06 30;62(6):823-828. Epub 2020 Oct 30.

German Cancer Consortium (DKTK), Partner Site Freiburg, Germany

Accurate delineation of the intraprostatic gross tumor volume (GTV) is a prerequisite for treatment approaches in patients with primary prostate cancer (PCa). Prostate-specific membrane antigen PET (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 tumor (GTV-CNN) in PSMA PET. The CNN (3D U-Net) was trained on the Ga-PSMA PET images of 152 patients from 2 different institutions, and the training labels were generated manually using a validated technique. The CNN was tested on 2 independent internal (cohort 1: Ga-PSMA PET, = 18 and cohort 2: F-PSMA PET, = 19) and 1 external (cohort 3: Ga-PSMA PET, = 20) test datasets. Accordance between manual contours and GTV-CNN was assessed with the Dice-Sørensen coefficient (DSC). Sensitivity and specificity were calculated for the 2 internal test datasets (cohort 1: = 18, cohort 2: = 11) using whole-mount histology. The 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 the 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 s 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 as a reference. This robust, accurate and fast technique may be implemented for treatment concepts in primary prostate cancer. 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
June 2021

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

J Nucl Med 2021 04 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049367PMC
April 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

Incidental primary breast cancer detected on surveillance Ga-DOTATATE PET/CT in a patient with metastatic neuroendocrine carcinoma.

Radiol Case Rep 2020 Aug 25;15(8):1344-1347. Epub 2020 Jun 25.

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 601 N. Caroline Street, Baltimore 21287, MD, USA.

We present a case of a 53-year-old woman with metastatic neuroendocrine tumor, presumed primary in the small intestine with metastases to the liver and mesenteric lymph nodes. The patient was being treated with lanreotide and followed with somatostatin receptor (SSTR)-targeted 68Ga-labeled 1,4,7,10-tetraazacyclododecane-', '','''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate (Ga-DOTATATE) positron emission tomography - computed tomography (PET/CT). On a follow-up exam, the patient's primary and metastatic disease had improved but she had new Ga-DOTATATE-avid lesions in the right breast and right axilla. Subsequent breast imaging workup and biopsy demonstrated a primary breast cancer and axillary lymph node metastasis.
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http://dx.doi.org/10.1016/j.radcr.2020.05.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322489PMC
August 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

Emerging Molecular Targets for Imaging of Atherosclerotic Plaque using Positron Emission Tomography.

Curr Radiopharm 2021 ;14(3):173-183

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

Positron-emission-tomography (PET) using the radiopharmaceutical F-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. To review and highlight recent evidence on the role of PET for atherosclerosis imaging using emerging radiotracers. 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 F-- sodium fluoride PET, CXCR4-targeted PET, and amyloid-β-targeted PET. 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 F-sodium fluoride PET and - to a lesser extent - CXCR4-targeted PET, whereas amyloid-β-targeted PET is still in its infancy. F-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 the 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
September 2021

The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care Toward Molecular Medicine.

J Nucl Med 2020 07 17;61(7):951-961. Epub 2020 Apr 17.

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

Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, toward the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been underrecognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection, and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecule-targeted procedures, in which specific therapeutic interventions require specific diagnostic guidance toward the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad blockbuster medication, toward a future of novel, individualized molecule-targeted and molecular imaging-guided therapies.
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http://dx.doi.org/10.2967/jnumed.119.240440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383072PMC
July 2020
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