Publications by authors named "Kambiz Rahbar"

77 Publications

[PSMA radioligand therapy could pose infrastructural challenges for nuclear medicine: results of a basic calculation for the capacity planning of nuclear medicine beds in the German hospital sector].

Nuklearmedizin 2021 Feb 2. Epub 2021 Feb 2.

Lehrstuhl für Management und Innovation im Gesundheitswesen, Universität Witten/Herdecke, Deutschland.

Background:  With the increasing use of the Lu-177-PSMA-RLT for the treatment of advanced castrate resistant prostate cancer (mCRPC), an estimation of the necessary therapy beds in nuclear medicine departments is of great importance in the view of the high number of cases of advanced prostate cancer, and as a basis to avoid a potentially infrastructure-related bottleneck for patient care in this field.

Methods:  The number of therapy beds available in German nuclear medicine departments was included in a basic calculation in view of the overall potential for therapy beds to be expected in the event of a possible approval of a therapeutic agent for the Lu-177-PSMA-RLT for mCRPC patients. A potential expansion of the Lu-PSMA-therapy indications was not taken into account.

Results:  The basic calculation shows for a nationwide nuclear medicine bed capacity of approx. 234 000 treatment days a relatively small bed reserve of approx. 19 000 nuclear medicine bed days, which corresponds to a reserve of 63 beds for the research question. There are regional differences in bed capacity: while for some federal states there is an under-capacity of nuclear medicine therapy beds with an approved Lu-177-PSMA-RLT, this is less the case for other federal states.

Discussion:  This basic calculation shows that the capacity of nuclear medicine therapy beds is likely to be very well utilized with a prospectively approved therapeutic agent for Lu-177-PSMA-RLT, and could even reach its limits in some German federal states. With a prospective expansion of the range of indications or the foreseeable clinical establishment of further therapeutic radiopharmaceuticals, the number of therapy beds could represent a bottleneck factor for the comprehensive patient treatment in the medium term.
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http://dx.doi.org/10.1055/a-1351-0030DOI Listing
February 2021

Prostate-specific Membrane Antigen-based Imaging of Castration-resistant Prostate Cancer.

Eur Urol Focus 2021 Jan 19. Epub 2021 Jan 19.

West German Cancer Center; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

Context: Positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC). There is now growing evidence regarding the value of PSMA-PET in patients with advanced PC.

Objective: To review the value of PSMA-PET/computed tomography (CT) in the context of castration-resistant PC (CRPC).

Evidence Acquisition: A search of the PubMed database using the terms "PSMA PET castration resistant prostate cancer" (years 2011-2020) was performed. Reviews, case reports/series, non-English articles, preclinical studies, access-restricted studies, and studies on PSMA radioligand therapy without further analysis of PSMA-PET parameters were subsequently excluded.

Evidence Synthesis: Compared to conventional imaging, PSMA-PET better identifies the true extent of CRPC, especially nonmetastatic CRPC. The clinical benefit of this stage migration is still unclear and needs to be evaluated in further studies. High accuracy of PSMA-PET holds promise for better, PET-guided metastasis-directed treatment in patients with oligometastatic CRPC. PSMA-PET is an essential eligibility criterion for [Lu]-PSMA theranostic applications. Preliminary evidence indicates the value of PSMA-PET for the assessment of treatment responses.

Conclusions: Among other applications, PSMA-PET offers more precise staging for nonmetastatic CRPC. In particular, target localization for metastasis-directed therapy and target expression assessment for PSMA radioligand therapy also hold promise. Potential translation of this diagnostic tool into an oncologic benefit needs to be defined in future trials.

Patient Summary: This review describes how prostate-specific membrane antigen positron emission tomography (PSMA-PET), a new sensitive imaging tool for prostate cancer, might help to guide clinicians in making treatment decisions for advanced prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2021.01.002DOI Listing
January 2021

Do fasting or high caloric drinks affect the physiological uptake of fluorine-18 prostate-specific membrane antigen-1007 in liver and bowel?

World J Nucl Med 2020 Jul-Sep;19(3):220-223. Epub 2019 Nov 7.

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

Recently introduced fluorine-18 prostate-specific membrane antigen-1007 (F-PSMA-1007) for imaging prostate cancer has an intense physiologic liver uptake and biliary excretion. The aim of the present study was to evaluate the effect of different dietary conditions on this physiological uptake. Forty consecutive prostate cancer patients were scanned with F-PSMA-1007 positron emission tomography/computed tomography at different dietary conditions. In addition to a blinded read scoring, tracer uptake intensities (standardized uptake values [SUVs]) were measured in the liver and small bowel. There was no significant difference in liver and small-bowel uptake between different patient groups. Wilcoxon signed-rank tests revealed no significant difference of the median mean SUV of the liver or maximum SUV of the horizontal part of the duodenum between different dietary conditions groups. A dietary preparation of patients by fasting or the attempt to clear liver activity by high caloric drinks does not have a significant effect on tracer uptake in the liver or in the small bowel.
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http://dx.doi.org/10.4103/wjnm.WJNM_6_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745857PMC
November 2019

Optimizing PSMA Radioligand Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Meta-Analysis.

Int J Mol Sci 2020 Nov 28;21(23). Epub 2020 Nov 28.

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori (IRST) IRCCS, 7014 Meldola, Italy.

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.
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http://dx.doi.org/10.3390/ijms21239054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730994PMC
November 2020

Analysis of failed therapy evaluations in radioembolization of primary and secondary liver cancers.

J Cancer Res Clin Oncol 2020 Nov 6. Epub 2020 Nov 6.

Institute of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Munster, Germany.

Purpose: To analyze patients' characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after Tc-labeled macroaggregated albumin (Tc-MAA) evaluation.

Methods: In this retrospective single-center cohort, all patients undergoing Tc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either "TARE" or "no TARE" group. Patients' characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed.

Results: 436 patients [male = 248, female = 188, median age 62 (23-88) years] with Tc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in "no TARE" compared to "TARE" group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of Tc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031).

Conclusion: A substantial number of patients are precluded from TARE following Tc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.
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http://dx.doi.org/10.1007/s00432-020-03443-zDOI Listing
November 2020

Repeated radioembolization in advanced liver cancer.

Ann Transl Med 2020 Sep;8(17):1055

Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany.

Background: To evaluate safety and clinical outcome of repeated transarterial Y (yttrium) radioembolization (TARE) in primary and metastatic liver cancer.

Methods: Between 2009 and 2018, n=288 patients underwent TARE for treatment of malignant liver disease in a tertiary care hospital. This retrospective single center study analyzed the safety and outcome of patients (n=11/288) undergoing repeated resin microsphere TARE. Included patients suffered from hepatocellular carcinoma (n=3), colorectal cancer (n=2), breast cancer (n=2), intrahepatic cholangiocarcinoma (n=3), and neuroendocrine carcinoma (n=1). All patients had shown either partial response (n=9) or stable disease (n=2) after first TARE. Lab parameters, response assessed by the Response Evaluation Criteria in Solid Tumors (mRECIST/RECIST) at 3 months and overall survival was analyzed. Additionally, patients with repeated TARE were compared to a matched control group (n=56) with single TARE therapy. Kaplan Meier analysis was performed to analyze survival.

Results: Patients after repeated TARE showed similar increase in lab parameters as compared to their first TARE. No case of radioembolization induced liver disease was observed. While n=5/11 patients showed a partial response and n=4/11 patients a stable disease after repeated TARE, only n=2/11 patients suffered from progressive disease. Median overall survival was 20.9±11.9 months for the repeated TARE group while it was 5.9±16.2 months for the control group.

Conclusions: Repeated Y TARE is safe and can be of benefit for patients yielding a comparable degree of local disease control compared to patients with singular TARE.
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http://dx.doi.org/10.21037/atm-20-2658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575953PMC
September 2020

EFFICACY OF 90Y-RADIOEMBOLIZATION IN METASTATIC COLORECTAL CANCER DEPENDING ON THE PRIMARY TUMOR SIDE.

Dig Dis 2020 Nov 3. Epub 2020 Nov 3.

Metastatic colorectal cancer (mCRC) is associated with different molecular biology, clinical characteristics and outcome depending on the primary tumor localization. We aimed to evaluate the effectiveness of 90Y-radioembolization (RE) for therapy of colorectal liver metastases depending on the primary tumor side. We performed a retrospective analysis of n=73 patients with mCRC and RE in our university liver center between 2009 and 2018. Patients were stratified according to the primary tumor side (left vs. right hemicolon), treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) at follow-up after 3 months. Kaplan-Meier analysis was performed to analyze survival followed by Cox regression to determine independent prognostic factors for survival. Prior to RE all patients had received systemic therapy, with either stable or progressive disease, but no partial or complete response. In n=22/73 (30.1%) patients the primary tumor side was in the right colon, in n=51/73 (69.9%) patients in the left colon. Hepatic tumor burden was ≤25% in n=36/73 (49.3%) patients and >25% in n=37/73 (50.7%) patients. At 3 months, n=21 (33.8%) patients showed treatment response [n=2 (3.2%) complete response, n=19 (30.6%) partial response], n=13 (21.0%) stable disease, and n=28 (45.2%) progressive disease after RE. The median survival in case of primary tumor side in the left colon was significantly higher than for primary tumors in the right colon (8.7 vs. 6.0 months, p=0.033). The median survival for a hepatic tumor burden ≤25% was significantly higher compared with >25% (13.9 vs. 4.3 months, p<0.001). The median overall survival was 6.1 months. The median survival after RE in hepatic-metastatic CRC depends on the primary tumor side and the pre-procedural hepatic tumor burden.
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http://dx.doi.org/10.1159/000512744DOI Listing
November 2020

PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis.

Eur J Nucl Med Mol Imaging 2020 Sep 24. Epub 2020 Sep 24.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.

Introduction: [Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy.

Methods: A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUV), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUV were quantified for each patient. Log2 transformation was used for regressions.

Results: Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value.

Conclusion: PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.
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http://dx.doi.org/10.1007/s00259-020-05040-1DOI Listing
September 2020

Re: Medical Event: Accidental Oral Administration of 177Lu-PSMA to a Patient With Hyperthyroidism.

Clin Nucl Med 2020 Sep 15. Epub 2020 Sep 15.

Department of Nuclear Medicine Klinikum Westfalen, Dortmund, Germany.

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http://dx.doi.org/10.1097/RLU.0000000000003276DOI Listing
September 2020

Diagnostic Accuracy of F-PSMA-1007 PET/CT Imaging for Lymph Node Staging of Prostate Carcinoma in Primary and Biochemical Recurrence.

J Nucl Med 2021 Feb 17;62(2):208-213. Epub 2020 Aug 17.

Department of Nuclear Medicine, University Hospital, Heidelberg, Germany

Prostate-specific membrane antigen (PSMA)-ligand PET/CT is performed on patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. On the basis of clinical results, F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Ninety-six patients with prostate cancer underwent F-PSMA-1007 PET/CT followed by either radical prostatectomy with lymphadenectomy or salvage lymphadenectomy. The histologic findings of PSMA PET-positive nodes were analyzed retrospectively. A lesion-based and patient-based analysis was performed comparing all positive lesions and only lesions larger than 3 mm on histopathology. Of the patients, 90.6% received F-PSMA-1007 PET/CT for staging before the primary treatment, whereas 9.4% underwent imaging for biochemical recurrence. In 34.4% of the cohort, positive lymph nodes were present on imaging. In total, 1,746 lymph nodes were dissected in 96 patients. F-PSMA-1007 PET had a lesion-based sensitivity of 81.7%, a specificity of 99.6%, a positive predictive value of 92.4%, and a negative predictive value of 98.9% for detecting positive lymph nodes larger than 3 mm. In the analysis of all malignant nodes regardless of size, the overall sensitivity, specificity, positive predictive value, and negative predictive value on lesion-based analysis were 71.2%, 99.5%, 91.3%, and 97.9%, respectively. The patient-based analysis showed a sensitivity of 85.9% and a specificity of 99.5% for lymph nodes larger than 3 mm. F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases.
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http://dx.doi.org/10.2967/jnumed.120.246363DOI Listing
February 2021

Somatostatin Receptor-Targeted Radioligand Therapy in Head and Neck Paraganglioma.

World Neurosurg 2020 Nov 31;143:e391-e399. Epub 2020 Jul 31.

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

Objective: Surgical resection is the therapy of choice in head and neck paraganglioma but is associated with considerable morbidity. For treatment of inoperable or progressive disease, less aggressive adjuvant options are warranted. This study assessed effectiveness and safety of peptide receptor radionuclide therapy (PRRT) with lutetium-177-DOTATATE for head and neck paraganglioma with emphasis on response assessment.

Methods: A retrospective analysis of 7 patients with head and neck paraganglioma treated with PPRT between May 2014 and October 2016 was performed. Three patients had jugulotympanic paraganglioma, 3 patients had carotid body tumors, and 1 patient had a combination of both. Patients underwent PRRT after discussion in the local tumor board regarding progressive disease, inoperability, or lack of other adjuvant options. All patients underwent 3-5 cycles of PRRT. Treatment response was evaluated by gallium-68-DOTATATE positron emission tomography/computed tomography and contrast-enhanced computed tomography or magnetic resonance imaging. Outcome measures were two-dimensional tumor diameters and total tumor volumes.

Results: Median patient age was 60 years (interquartile range: 14-84 years). All patients had stable disease at posttherapy assessment. Decreasing tumor volumes were found in 4 patients. Clinical symptoms improved in 2 patients. No progression or adverse events occurred during a median follow-up of 39 months (interquartile range: 35-47 months).

Conclusions: Somatostatin receptor-targeted therapy using lutetium-177-DOTATATE shows promising effectiveness with a high safety profile. Patients in whom surgical morbidity outweighs oncologic benefit should be informed about PRRT as a treatment option.
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http://dx.doi.org/10.1016/j.wneu.2020.07.165DOI Listing
November 2020

Response assessment of somatostatin receptor targeted radioligand therapies for progressive intracranial meningioma.

Nuklearmedizin 2020 Sep 20;59(5):348-355. Epub 2020 Jul 20.

Department of Nuclear Medicine, University Hospital Münster, Germany.

Background:  In somatostatin receptor (SSTR) expressing progressive meningioma, peptide receptor radionuclide therapy (PRRT) has shown effect in small clinical series. However, standardized treatment and response assessment protocols are lacking. We present our experience on PPRT with Lu-DOTATATE in progressive meningioma with a special emphasis on state-of-the-art response assessment.

Methods:  Retrospective analysis on PRRT with Lu-DOTATATE from 2015 to 2019. Pre- and post-therapy imaging was performed using MRI and Ga-DOTATATE-PET for standard bidimensional and volumetric analyses, respectively, following novel RANO guidelines.

Results:  Seven patients with progressive intracranial meningioma (median age 73 years, interquartile range 60-76; 5 WHO II, 2 WHO I; 5 multifocal) received a median of 4 cycles 2 3 4 of PRRT with Lu-DOTATATE in eight-week intervals. Three patients did not undergo post-therapy Ga-DOTATATE-PET due to early symptomatic progression and subsequent cessation of PRRT. After completion of 4 PRRT cycles volumetric PET imaging showed stable disease in two of four patients. According to bidimensional MRI response assessment, only one patient was stable. Progression free survival at six months was 42.9 %.

Conclusion:  In this heterogeneous collective of seven patients with progressive meningioma, 177Lu-DOTATATE therapies showed heterogeneous effectiveness. PET-based volumetric assessment should be used for response assessment in PRRT additionally to bidimensional imaging.
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http://dx.doi.org/10.1055/a-1200-0989DOI Listing
September 2020

Analysis of PSMA expression and outcome in patients with advanced Prostate Cancer receiving Lu-PSMA-617 Radioligand Therapy.

Theranostics 2020 19;10(17):7812-7820. Epub 2020 Jun 19.

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

PSMA-PET-CT enables measuring molecular expression of prostate-specific membrane antigen (PSMA) , which is the target molecule of Lu-PSMA-617 (Lu-PSMA) therapy. However, the correlation of PSMA expression and overall survival (OS) in patients treated with Lu-PSMA therapy is currently unclear; especially with regard to coexistence of high and low PSMA expressing metastases. To this end, this retrospective single arm study elucidates the correlation of PSMA expression and overall survival in patients treated with Lu-PSMA therapy. Additionally, PET based criteria to define low PSMA expression were explored. Eighty-five patients referred to Lu-PSMA therapy were included in the analysis. Pretherapeutic Ga-PSMA-PET-CT scans were available for all patients. SUV of the highest PSMA expressing metastasis (PSMA), SUV of the lowest PSMA expressing metastasis (PSMA), and average SUV of all metastases (PSMA) amongst other PET parameters were measured for each patient. A log-rank cutoff-finder was used to determine low (lowPSMA) and high (highPSMA) average PSMA expression as well as low (lowPSMA) and high (highPSMA) minimal PSMA expression. PSMA was a significant prognosticator of overall survival in contrast to PSMA (HR: 0.959; p = 0.047 vs. HR: 0.992; p = 0.231). Optimal log rank cut-offs were: PSMA = 14.3; PSMA = 10.2. Patients with low average PSMA expression (lowPSMA) had significantly shorter survival compared to those with high average expression (highPSMA) (5.3 vs. 15.1 months; p < 0.001; HR: 3.738, 95%CI = 1.953-7.154; p < 0.001). Patients with low PSMA expressing metastases (lowPSMA) had shorter survival compared to those without a low PSMA expressing metastasis (highPSMA) (p = 0.003; 7.9 months vs. 21.3; HR: 4.303, 95%CI = 1.521-12.178; p = 0.006). Patients that were classified as highPSMA but with lowPSMA had an intermediate overall survival (11.4 months; longer compared to lowPSMA, 5.3 months, p = 0.002; but shorter compared to highPSMA, 21.3 months, p = 0.02). Low average PSMA expression is a negative prognosticator of overall survival. Absence of low PSMA expressing metastases is associated with best overall survival and the maximum PSMA expression seems not suited to prognosticate overall survival. Low PSMA expression might therefore be a negative prognosticator for the outcome of patients treated with Lu-PSMA therapy. Future studies are warranted to elucidate the degree of low PSMA expression tolerable for Lu-PSMA therapy.
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http://dx.doi.org/10.7150/thno.47251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359095PMC
June 2020

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving Lu-PSMA-617 Radioligand Therapy.

Theranostics 2020 18;10(17):7645-7655. Epub 2020 Jun 18.

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

Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates. Nineteen patients, median age 68.8 years (range: 56.9 - 83.3) with mCRPC were included in this study. We performed baseline analysis of clinical parameters based on PSMA PET/CT, (metabolic tumor volume (MTV), total tumor volume (TTV)), serum PSA, ALP, LDH and gene expression analysis of circulating tumor cells (expression of AR full length (AR-FL), AR splice variant 7 (AR-V7), PSA and PSMA) as well as common markers for neuroendocrine differentiation (NED). Patients presented with bone, lymph node, and visceral metastases (89%, 68%, and 21%, respectively). All patients were pretreated with docetaxel, either abiraterone or enzalutamide, or both. Biochemical response in terms of PSA decline ≥50 or ≥30% was observed in 42% and 63%, respectively. There were significant correlations between PSA and PSMA mRNA expression, as well as tumor volumes (both MTV and TTV), AR-FL and AR-V7 mRNA expression. However, there was no correlation with response to PSMA treatment. Furthermore, none of these parameters was significantly correlated with baseline serum PSA values. Common NED markers were shown to be specifically high expressed and revealed impact on OS independent from AR-V7 gene expression. We demonstrate that AR-FL and its splice variant AR-V7 might serve as prognostic biomarkers displaying high tumor burden in mCRPC patient prior to PSMA-RLT. Contrary, PSMA, which has been discussed as a biomarker for PSMA targeted treatment, does not display strong prognostic ability - at least on the mRNA level. Surprisingly, none of these parameters correlates to response to PSMA treatment. In contrast, commom NED markers such as SYP and ENO2 as well as FOXA1 expression level seem to predict OS, but not PFS, more reliably. We admit that a limitation of our study is the focus on mRNA expression of potential biomarkers only. Further investigations analyzing the potential role of protein expression of these markers are therefore warranted.
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http://dx.doi.org/10.7150/thno.44556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359074PMC
June 2020

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

Eur J Nucl Med Mol Imaging 2021 Jan 8;48(1):113-122. Epub 2020 May 8.

Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.

Introduction: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with Lu-PSMA-617.

Materials And Methods: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated.

Results: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.

Conclusion: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.
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http://dx.doi.org/10.1007/s00259-020-04797-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835179PMC
January 2021

Semiautomatically Quantified Tumor Volume Using Ga-PSMA-11 PET as a Biomarker for Survival in Patients with Advanced Prostate Cancer.

J Nucl Med 2020 12 24;61(12):1786-1792. Epub 2020 Apr 24.

Department of Nuclear Medicine, University Hospital Münster, Münster, Germany

Prostate-specific membrane antigen (PSMA)-targeting PET imaging is becoming the reference standard for prostate cancer staging, especially in advanced disease. Yet, the implications of PSMA PET-derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be because semiautomated quantification of whole-body tumor volume as a PSMA PET biomarker is an unmet clinical challenge. Therefore, in the present study we propose and evaluate a software that enables the semiautomated quantification of PSMA PET biomarkers such as whole-body tumor volume. The proposed quantification is implemented as a research prototype. PSMA-accumulating foci were automatically segmented by a percental threshold (50% of local SUV). Neural networks were trained to segment organs in PET/CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semiautomatically excluded from the analysis. Pretherapeutic PSMA PET/CTs of 40 consecutive patients treated with Lu-PSMA-617 were evaluated in this analysis. The whole-body tumor volume (PSMA), SUV, SUV, and other whole-body imaging biomarkers were calculated for each patient. Semiautomatically derived results were compared with manual readings in a subcohort (by 1 nuclear medicine physician). Additionally, an interobserver evaluation of the semiautomated approach was performed in a subcohort (by 2 nuclear medicine physicians). Manually and semiautomatically derived PSMA metrics were highly correlated (PSMA: = 1.000, < 0.001; SUV: = 0.988, < 0.001). The interobserver agreement of the semiautomated workflow was also high (PSMA: = 1.000, < 0.001, interclass correlation coefficient = 1.000; SUV: = 0.988, < 0.001, interclass correlation coefficient = 0.997). PSMA (ml) was a significant predictor of overall survival (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006, = 0.002) and remained so in a multivariate regression including other biomarkers (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006 = 0.004). PSMA is a promising PSMA PET biomarker that is reproducible and easily quantified by the proposed semiautomated software. Moreover, PSMA is a significant predictor of overall survival in patients with advanced prostate cancer who receive Lu-PSMA-617 therapy.
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http://dx.doi.org/10.2967/jnumed.120.242057DOI Listing
December 2020

Incremental diagnostic value of [F]tetrafluoroborate PET-CT compared to [I]iodine scintigraphy in recurrent differentiated thyroid cancer.

Eur J Nucl Med Mol Imaging 2020 10 4;47(11):2639-2646. Epub 2020 Apr 4.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Introduction: Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([I]iodine) or limited availability ([I]iodine). In contrast, [F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC. The aim of the present study was to compare the diagnostic performance of [F]TFB-PET to the clinical reference standard [I]iodine scintigraphy in patients with recurrent DTC.

Methods: Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [F]FDG-PET-CT was present for 21 patients. Histological verification of [F]TFB positive findings was available in 4 patients.

Results: [F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [I]iodine scintigraphy was changed: [F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [F]TFB-PET-CT/MRI with [F]FDG-PET-CT (64%).

Conclusion: In the present cohort, [F]TFB-PET shows higher sensitivity and accuracy than [I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [F]TFB-PET with [F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [F]TFB-PET in recurrent DTC are warranted.
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http://dx.doi.org/10.1007/s00259-020-04727-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515952PMC
October 2020

Radioligand therapy using [Lu]Lu-PSMA-617 in mCRPC: a pre-VISION single-center analysis.

Eur J Nucl Med Mol Imaging 2020 08 16;47(9):2106-2112. Epub 2020 Feb 16.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.

Background: Radioligand therapy with [Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks).

Methods: A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test.

Results: There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and - 40.2% vs. - 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups.

Conclusion: Higher cumulated doses of [Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [Lu]Lu-PSMA-617 as a way to personalized medicine.
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http://dx.doi.org/10.1007/s00259-020-04703-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338828PMC
August 2020

Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization.

J Clin Med 2019 Dec 25;9(1). Epub 2019 Dec 25.

Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany.

Purpose: To evaluate factors associated with survival following transarterial Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC).

Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan-Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival.

Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29-88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1-12.9 months). Due to loss in follow-up, = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume ( = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, = 0.002). No case of radiation-induced liver disease was observed.

Discussion: Survival after Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.
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http://dx.doi.org/10.3390/jcm9010056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020033PMC
December 2019

The role of additional late PSMA-ligand PET/CT in the differentiation between lymph node metastases and ganglia.

Eur J Nucl Med Mol Imaging 2020 03 21;47(3):642-651. Epub 2019 Dec 21.

Department of Nuclear Medicine, Bern University Hospital, Freiburgstrasse 18, 3010, Bern, Switzerland.

Purpose: Differentiating between prostate cancer (PC) lesions and benign structures which exhibit radiotracer uptake in PSMA-ligand PET/CT can be challenging. Additional late imaging has been shown to be a powerful method for the discrimination between PC and non-PC lesions, owing to the increasing tracer uptake of the former. Nevertheless, there are no pre-existing studies which describe the dynamic tracer uptake for ganglia, which this present study aims to address.

Methods: Fifty consecutive patients with PC who received standard and late Ga-PSMA-11-PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background indicative for ganglia as well as PC lesions were analysed with regard to their maximum standardised uptake values (SUVmax) and localisation.

Results: Overall, 86 PSMA-positive ganglia were identified in 70% (n = 35) of the patients. Five ganglia exhibited PSMA avidity at late imaging only, and three at standard imaging only. A total of 66 lesions suggestive for PC were detected in 44 patients (88%), of which 45% (n = 30) were morphologically identified as lymph nodes (LN), the remainder being locally recurrent lesions or bone metastases. No solid organ metastases were present in our cohort. At late scanning, 73% of the LN exhibited an increase in SUVmax, whereas 65% of the ganglia exhibited a decreasing or stable SUVmax.

Conclusion: Whereas the presence of increasing tracer uptake in potential PC lesions can provide additional data about the likelihood of malignancy, increasing SUVmax alone does not reliably differentiate between ganglia and PC lesions and is a potential diagnostic pitfall. We therefore recommend high-resolution CT to enable morphological characterisation of ganglia.
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http://dx.doi.org/10.1007/s00259-019-04552-9DOI Listing
March 2020

PSMA-Based Theranostics: A Step-by-Step Practical Approach to Diagnosis and Therapy for mCRPC Patients.

Semin Nucl Med 2020 01 21;50(1):98-109. Epub 2019 Aug 21.

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

To date, several papers have been published about prostate-specific membrane antigen (PSMA)-based radioligand diagnostic and therapeutic approaches. This paper mainly provides information for nuclear medicine physicians that are clinically engaged in the diagnosis and treatment of prostate cancer patients. It aims to present the utility of PSMA imaging and therapy in a step-by-step practical approach; thus, it does not discuss radiochemistry and the molecular basics of PSMA.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.07.003DOI Listing
January 2020

Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer-a modified protocol compared with the common protocol.

Eur J Nucl Med Mol Imaging 2020 03 1;47(3):624-631. Epub 2019 Nov 1.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Purpose: Ga-PSMA-11 PET/CT is commonly performed at 1 h post injection (p.i.). However, various publications have demonstrated that most prostate cancer (PC) lesions exhibit higher contrast at later imaging. The aim of this study was to compare the "common" protocol of Ga-PSMA-11 PET/CT with a modified protocol.

Methods: In 2017, we used the following scanning protocol for Ga-PSMA-11 PET/CT in patients with recurrent PC: acquisition at 1 h p.i. without further preparations. From 2018, all scans were conducted at 1.5 h p.i. In addition, patients were orally hydrated with 1 L of water 0.5 h p.i. and were injected with 20 mg of furosemide 1 h p.i. Both protocols including 112 patients (2017) and 156 (modified protocol in 2018) were retrospectively compared. Rates of pathologic scans, maximum standardized uptake values (SUVmax), and tumor contrast (ratio lesion-SUVmax/background-SUVmean) as well as average standardized uptake values (SUVmean) of urinary bladder were analyzed.

Results: Both tumor contrast and tracer uptake were significantly (p < 0.001) higher in the novel protocol. Although statistically not significant, the rates of pathologic scans were also higher in the modified protocol: 76.3% vs. 68.8% for all PSA values including 38.9% vs. 25.0% for PSA < 0.5 ng/ml and 60.0% vs. 56.7% for PSA > 0.5-≤ 2.0 ng/ml. Average SUVmean of the urinary bladder was significantly (p < 0.001) lower with the modified protocol.

Conclusions: The modified protocol, which includes a combination of delayed image acquisition at 1.5 h p.i., hydration, and furosemide resulted in higher tumor contrast and seems to have the potential to increase the rates of pathological scans, especially at low PSA levels.
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http://dx.doi.org/10.1007/s00259-019-04548-5DOI Listing
March 2020

Dynamic patterns of [Ga]Ga-PSMA-11 uptake in recurrent prostate cancer lesions.

Eur J Nucl Med Mol Imaging 2020 01 18;47(1):160-167. Epub 2019 Oct 18.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, 3010, Bern, Switzerland.

Purpose: Dual-time point PET/CT scanning with [Ga]Ga-PSMA-11 in the diagnosis of prostate cancer (PC) has been advanced as a method to increase detection of PC lesions, particularly at early stages of biochemical recurrence and as a potential means to aid the discrimination between benign and pathological prostate-specific membrane antigen (PSMA) uptake. However, the assumption that all PC lesions uniformly exhibit increasing tracer uptake at delayed imaging has not yet been investigated, which this present study aims to address.

Methods: One hundred consecutive patients with biochemically recurrent PC who received standard and late [Ga]Ga-PSMA-11 PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background were analysed with regard to their maximum standardised uptake values at standard and late images (SUVmax) and characterised according to their morphological characteristics.

Results: Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging.

Conclusion: A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.
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http://dx.doi.org/10.1007/s00259-019-04545-8DOI Listing
January 2020

Additional Local Therapy for Liver Metastases in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Systemic PSMA-Targeted Therapy.

J Nucl Med 2020 05 10;61(5):723-728. Epub 2019 Oct 10.

Department of Nuclear Medicine, University Hospital Münster, Münster, Germany

The aim of this study was to evaluate the efficacy of Lu-prostate-specific membrane antigen (PSMA)-617 (Lu-PSMA) and selective internal radiation therapy (SIRT) for the treatment of liver metastases of castration-resistant prostate cancer. Safety and survival of patients with metastatic castration-resistant prostate cancer and liver metastases assigned to Lu-PSMA alone ( = 31) or in combination with SIRT ( = 5) were retrospectively analyzed. Additionally, a subgroup ( = 10) was analyzed using morphologic and molecular response criteria. Median estimated survival was 5.7 mo for Lu-PSMA alone and 8.4 mo for combined sequential Lu-PSMA and SIRT. Lu-PSMA achieved discordant therapy responses with both regressive and progressive liver metastases in the same patient (best vs. worst responding metastases per patient: -35% vs. +63% diameter change; < 0.05). SIRT was superior to Lu-PSMA for the treatment of liver metastases (0% vs. 56% progression). The combination of Lu-PSMA and SIRT is efficient and feasible for the treatment of advanced prostate cancer. Lu-PSMA alone seems to have limited response rates in the treatment of liver metastases.
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http://dx.doi.org/10.2967/jnumed.119.233429DOI Listing
May 2020

Is the Vision of Radioligand Therapy for Prostate Cancer Becoming a Reality? An Overview of the Phase III VISION Trial and Its Importance for the Future of Theranostics.

J Nucl Med 2019 11 26;60(11):1504-1506. Epub 2019 Aug 26.

Department of Genitourinary Oncology Service and Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Prostate-specific membrane antigen (PSMA) is of considerable interest as a target for diagnostics and therapy of prostate cancer patients. PSMA-targeted imaging has demonstrable value in guiding the management of the clinical evolution of prostatic cancer. The use of PSMA-targeted therapy using Lu-labeled PSMA-617 is similarly effective and is progressing toward approval. The phase III VISION trial represents the largest well-designed and executed study of a theranostic pair. This article provides an overview of the phase III trial and delineates the different study arms and their implications in the assessment of efficacy. The VISION (phase III) trial will provide data of critical value to the field of theranostics and especially the field of prostatic cancer management.
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http://dx.doi.org/10.2967/jnumed.119.234054DOI Listing
November 2019

EANM procedure guidelines for radionuclide therapy with Lu-labelled PSMA-ligands (Lu-PSMA-RLT).

Eur J Nucl Med Mol Imaging 2019 Nov 22;46(12):2536-2544. Epub 2019 Aug 22.

Department of Nuclear Medicine, |Universitätsklinikum Essen, Essen, Germany.

Prostate-specific membrane antigen (PSMA) is expressed in most prostate cancers and can be identified by PSMA-ligand imaging, which has already become clinically accepted in several countries in- and outside Europe. PSMA-directed radioligand therapy (PSMA-RLT) with Lutetium-177 (Lu-PSMA) is currently undergoing clinical validation. Retrospective observational data have documented favourable safety and striking clinical responses. Recent results from a prospective clinical trial (phase II) have been published confirming high response rates, low toxicity and reduction of pain in metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed after conventional treatments. Such patients typically survive for periods less than 1.5 years. This has led some facilities to adopt compassionate or unproven use of this therapy, even in the absence of validation within a randomised-controlled trial. As a result, a consistent body of evidence exists to support efficacy and safety data of this treatment. The purpose of this guideline is to assist nuclear medicine specialists to deliver PSMA-RLT as an "unproven intervention in clinical practice", in accordance with the best currently available knowledge.
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http://dx.doi.org/10.1007/s00259-019-04485-3DOI Listing
November 2019

Second line chemotherapy and visceral metastases are associated with poor survival in patients with mCRPC receiving Lu-PSMA-617.

Theranostics 2019 9;9(17):4841-4848. Epub 2019 Jul 9.

Department of Nuclear Medicine, Münster University Hospital.

The purpose of this study was to identify previous treatments and biomarker profile features that prognosticate overall survival (OS) in patients with mCRPC receiving Lu-PSMA-617. 109 mCRPC patients treated with a median of 3 cycles of Lu-PSMA-617 were included. Data were analyzed according to OS as well as PSA response patterns with regard to prior therapies, laboratory biomarkers and metastatic extent in univariate as well as multivariate Cox's proportional hazards models. PSA decline was assessed using the lowest PSA levels after the first cycle of therapy (initial PSA response) and during the entire observation period (best PSA response). In total, 54 patients (49.5%) died during the observation period. First and second line chemotherapy were performed in 85% and 26%, and Abiraterone and Enzalutamide were administered in 83% and 85%, respectively. Any initial PSA decline occurred in 55% while 25% showed a PSA decline of ≥50%. The median estimated OS was 9.9 months (95% CI: 7.2-12.5) for all patients. Any initial decline of PSA was associated with significantly prolonged OS (15.5 vs. 5.7 months, 0.002). Second line cabazitaxel chemotherapy (6.7 15.7 months, 0.002) and presence of visceral metastases (5.9 16.4 months, <0.001) were associated with shorter OS. Only visceral metastases remained significant in a multivariate analysis. Lu-PSMA-617 is an effective therapy for patients with mCRPC. However, the present data indicate that its beneficial effects on OS are strongly influenced by pretreatment (history of second line chemotherapy with cabazitaxel) and the presence of visceral metastases at onset of Lu-PSMA-617 treatment.
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http://dx.doi.org/10.7150/thno.35759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691377PMC
August 2020

FDG-PET proves to be reliable in the diagnostic workup of a rare cardiac hemangioma.

J Card Surg 2019 Oct 2;34(10):1097-1099. Epub 2019 Aug 2.

Department of Nuclear Medicine, University Hospital Münster, Germany.

The noninvasive characterization of cardiac tumors is of clinical importance for surgical resection planning. Conventional radiological examinations like cardiac computed tomography (CT) or magnetic resonance imaging (MRI) may be misleading as benign cardiac lesions can present features suspicious for malignancy. Moreover, the low prevalence of cardiac tumors may additionally hamper a sound diagnosis. However, fluorodeoxyglucose-positron emission tomography (FDG-PET) has proven to be a reliable tool for cardiac tumor characterization. Here, FDG-PET/CT imaging of a 50-year-old man suffering from a cardiac tumor is presented. Despite CT and MRI signs of malignancy, FDG-PET characterized the tumor as benign. Histology confirmed the FDG-PET prediction and revealed a pericardial capillary hemangioma. Thereby, it seems important to integrate FDG-PET in the diagnostic workup of cardiac tumors.
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http://dx.doi.org/10.1111/jocs.14197DOI Listing
October 2019

A Self-Fulfilling Prophecy: Comparing Lu-PSMA Radioligand Therapy in Taxane-Naïve Versus Posttaxane Metastasized Prostate Cancer Patients?

J Nucl Med 2019 10 29;60(10):1494. Epub 2019 Mar 29.

University Hospital Muenster Albert-Schweitzer-Campus 1 48149 Münster, Germany E-mail:

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http://dx.doi.org/10.2967/jnumed.119.228742DOI Listing
October 2019

Detection of Local Relapse of Prostate Cancer With 18F-PSMA-1007.

Clin Nucl Med 2019 Jun;44(6):e394-e395

From the Departments of Nuclear Medicine.

Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become a fundamental tool in the management of patients with prostate cancer, especially to rule out local recurrence after surgery or radiation. However, the assessment of the prostatic fossa is difficult due to the renal excretion of PSMA-targeted radionuclides. PET/CT studies using Ga-PSMA-11 PET/CT and F-PSMA-1007 of a 61-year-old man after radical prostatectomy are presented. This case illustrates that F-PSMA-1007 is an ideal radionuclide for the detection of local recurrence of prostate cancer and is superior to Ga-PSMA-11, especially in case of pelvic lesions.
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http://dx.doi.org/10.1097/RLU.0000000000002543DOI Listing
June 2019