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Introduction Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Methods Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Results Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.

BACKGROUND: In bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide. METHODS: Eighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models. RESULTS: In Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P50% [HR: 0.5 (0.3–0.7); P

In patients with bone metastatic castration-resistant prostate cancer (bmCRPC) on systemic treatment, it is difficult to differentiate between continuous rise of prostate specific antigen (PSA) representing progression, and PSA-surge, which is followed by clinical response or stable disease. The purpose of this study was to evaluate the prognostic value of dynamic changes of alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels as a predictor of clinical efficacy or therapeutic resistance of patients who do not show a sufficient initial PSA decline of ≥50% from baseline during early therapy with Enzalutamide.Forty-eight men with bmCRPC on Enzalutamide 07/2010-09/2019 with initially rising PSA were analyzed. We monitored PSA, LDH and ALP at week 0, 2, 4, and every 4 weeks thereafter and analyzed the correlation between ALP rising at 12 weeks with or without LDH-normalization and the association with survival. For this we used Kaplan Meier analysis and uni- and multivariate cox-regression models.In Kaplan-Meier analysis, ALP rising at 12 weeks with or without LDH-normalization was associated with significantly worse median progression-free survival (PFS) of 3 months vs. 5 months (Log rank P = 0.02) and 3 months vs. 5 months (P = 0.01), respectively and overall survival (OS) with 8 months vs. 15 months (P = 0.02) and 8 months vs. 17 months (P 0.01). In univariate analysis of PFS, ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization and application of Enzalutamide after chemotherapy showed a statistically significant association towards shorter PFS (hazard ratio (HR): 0.51, P = 0.04; HR: 0.48, P = 0.03; HR: 0.48, P = 0.03). Worse OS was significantly associated with ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization, and application of Enzalutamide after chemotherapy (HR: 0.47, P = 0.02; HR: 0.36, P 0.01; HR: 0.31, P 0.01). In multivariate analysis only the application of Enzalutamide after chemotherapy remained an independent prognostic factor for worse OS (HR: 0.36, P = 0.01).Dynamic changes of ALP (non-rise) and LDH (normalization) under therapy with Enzalutamide may be associated with clinical benefit, better PFS, and OS in patients with bmCRPC who do not show a PSA decline.

177Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from 68Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease &gt, 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy.

Simple Summary PSMA Therapy has recently become an additional therapeutic option in advanced prostate cancer. In the present study, the predictive and prognostic value of radiomic features from pretherapeutic PSMA PET-MRI are analyzed. Twenty-one patients with advanced prostate cancer underwent PSMA-therapy, including pretherapeutic PSMA PET-MRI. Radiomic features from PET- and MRI-sequences were extracted and processed to select the features differentiating responders and non-responders. Out of ten independent radiomic features differentiating between these two groups, the feature interquartile range from the T2 weighted images revealed the highest accuracy. PSA response and higher T2 interquartile range values might have impact on survival. This proof-of-concept study applies radiomic analysis to pretherapeutic PSMA PET-MRI before PSMA therapy, providing new parameters with potential predictive and prognostic value. Abstract 177Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from 68Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease > 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy.

Prostate-specific membrane antigen-PET/computed tomography (PSMA-PET/CT) is the investigation of choice for imaging prostate cancer. Demonstrating high diagnostic accuracy, PSMA-PET/CT detects disease at very early stages of recurrence, where the chances of a definitive cure may be at their greatest. A number of PSMA-radioligands are in established clinical routine, and there are currently only limited data and no single tracer can clearly be advocated over the others at present. Further clinical trial data, comparing and contrasting radiotracers and reporting outcome-based data are necessary to further increase the implementation of this very promising imaging modality.

Prostate-specific membrane antigen (PSMA) has been the subject of numerous studies within the last 3 decades. PSMA-targeted imaging and therapy have significantly changed the management of patients with prostate cancer in various disease stages, especially in advanced metastasized castration-resistant prostate cancer. Lutetium-177-conjugated PSMA-617 or PSMA-IT (Lu-PSMA) has shown promising results in multicenter retrospective and monocenter prospective trials. The aim of this review is to provide an overview of the history and current and future developments of PSMA-targeted therapy. A special focus of this review is on PSMA PET-guided management of patients receiving PSMA-targeted radioligand therapy.

PURPOSE Dual-time point PET/CT scanning with [68Ga]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 [68Ga]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.

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 (177Lu-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.

5002 Background: In the phase 3 VISION study, gallium (68Ga) gozetotide (68Ga-PSMA-11) PET/CT imaging was used to determine eligibility for lutetium (177Lu) vipivotide tetraxetan (177Lu-PSMA-617). Given that 177Lu-PSMA-617 targets PSMA, we assessed the association between quantitative PSMA imaging parameters and treatment outcomes. Methods: In VISION, adults with mCRPC with ≥ 1 PSMA-positive (+) and no PSMA-negative lesions meeting the exclusion criteria were enrolled. In this sub-study, the association between imaging data from pre-enrollment 68Ga-PSMA-11 PET/CT scans of pts in the 177Lu-PSMA-617 group and clinical outcomes was assessed. Imaging data meeting quality requirements were analyzed for 548/551 pts. PSMA expression was quantified by 5 PET parameters: PSMA+ lesions by region, mean standardized uptake value (SUVmean), maximum SUV (SUVmax), PSMA+ tumor volume, and tumor load (PSMA+ tumor volume × SUVmean). Parameters were extracted from the whole body and 4 regions. Association between PET parameters and radiographic progression-free survival (rPFS; primary objective), overall survival (OS), objective response rate (ORR), and prostate–specific antigen 50 (PSA50) response was assessed. Results: Most pts (92.7%) had PSMA uptake in bone. In both the whole-body and regional analyses, statistically significant associations of PSMA PET parameters to clinical outcomes were observed (whole-body data shown in Table). Higher whole-body SUVmean was associated with improved clinical outcomes; pts in the highest quartile (SUVmean: rPFS, ≥ 10.2; OS, ≥ 9.9) had a median rPFS and OS of 14.1 and 21.4 months, vs 5.8 and 14.5 months for those in the lowest quartile (< 6.0; < 5.7), respectively. Absence of PSMA+ lesions in bone, liver, and lymph node, and lower PSMA+ tumor load, were indicators of good prognosis. Conclusions: Higher SUVmean is strongly associated with improved outcomes with 177Lu-PSMA-617; clinical efficacy for different SUV levels vs the SoC arm is being assessed. Data support use of 68Ga-PSMA-11 PET/CT scan to identify pts who will benefit from PSMA-targeted radioligand therapy.[Table: see text]

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. 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. 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. 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. Mit der zunehmenden Verbreitung der Lu-177-PSMA-RLT zur Behandlung des fortgeschrittenen Prostatakarzinoms ist von Interesse, wie sich die Versorgungssituation mit Blick auf die hierfür nötigen nuklearmedizinischen Therapiebetten angesichts hoher Fallzahlen beim fortgeschrittenen PCa hypothetisch darstellen würde, und ob es hier potenziell zu einem infrastrukturbedingten Engpass für die Patientenversorgung kommen könnte. Das in deutschen Krankenhäusern verfügbare Angebot an nuklearmedizinischen Therapiebetten wurde dem bei etwaiger Zulassung eines Therapeutikums zur Lu-177-PSMA-RLT als Letztlinientherapie für mCRPC-Patienten perspektivisch insgesamt zu rechnenden nuklearmedizinischen Nachfragepotenzial an Therapiebetten in einer Basiskalkulation gegenübergestellt. Eine mögliche Ausweitung des Lu-PSMA-Indikationsspektrums wurde dabei nicht berücksichtigt. Nach der Basiskalkulation ergäbe sich bei einer bundesweit aktuellen nuklearmedizinischen Bettenkapazität von ca. 234 000 Behandlungstagen eine rechnerisch geringe Reserve von bundesweit ca. 19 000 nuklearmedizinischen Bettentagen, was umgerechnet einer Reserve von 63 Betten für die interessierende Fragestellung entspricht. Dabei zeigen sich regionale Unterschiede bei der Bettenkapazität: Während sich für einige Bundesländer eine rechnerische Unterkapazität an nuklearmedizinischen Therapiebetten bei Zulassung der Lu-177-PSMA-RLT andeutet, gilt dies für andere Bundesländer weniger. Diese Basiskalkulation zeigt, dass die Kapazität nuklearmedizinischer Therapiebetten bei einer etwaig zugelassenen Lu-177-PSMA-RLT für mCRPC sehr gut ausgelastet sein dürfte, in einigen Bundesländern sogar an ihre Grenzen stoßen könnte. Bei einer perspektivischen Ausweitung des Indikationsspektrums oder absehbar klinischen Etablierung weiterer therapeutischer Radiopharmaka könnte die Bettenzahl mittelfristig einen Engpassfaktor für das flächendeckende Behandlungsangebot darstellen.

BACKGROUND: Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 ((177)Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment. METHODS: We conducted an international, open-label, phase 3 trial evaluating (177)Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor–pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 ((68)Ga)–labeled PSMA-11 positron-emission tomographic–computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either (177)Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 ((223)Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment. RESULTS: From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. (177)Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P

Purpose The aim of this narrative review is to give an overview on current and emerging imaging methods and liquid biopsy for prediction and evaluation of response to PRRT. Current limitations and new perspectives, including artificial intelligence, are discussed. Methods A literature review of PubMed/Medline was performed with representative keywords. The search included articles published online through August 31, 2020. All searches were restricted to English language manuscripts. Results Peptide radio receptor therapy (PRRT) is a prospectively evaluated and approved therapy option in neuroendocrine tumors (NETs). Different ligands targeting the somatostatin receptor (SSTR) are used as theranostic pairs for imaging NET and for PRRT. Response assessment in prospective trials often relies on the morphological RECIST 1.1 criteria, based on lesion size in CT or MRI. The role of SSTR-PET and quantitative uptake parameters and volumetric data is still not defined. Monoanalyte tumor marker chromogranin A has a limited value for response assessment after PRRT. New emerging liquid biopsy techniques are offering prediction of response to PRRT and prognostic value. Conclusions New response criteria for NET patients undergoing PRRT will comprise multiparametric hybrid imaging and blood-based multianalyte markers. This represents tumor biology and heterogeneity.

Conventional imaging of low-volume disease (LVD) versus high-volume disease (HVD) is associated with survival in metastatic hormone-sensitive prostate cancer (mHSPC) according to the CHAARTED trial (Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer) and the STAMPEDE trial (Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy). We propose a compatible quantitative PSMA PET framework for disease volume assessment in mHSPC. Methods: Three PET centers screened their PSMA PET database for mHSPC patients. CT versus PSMA PET stage, lesion number, and classification of LVD versus HVD were determined by 1 masked reader; PSMA-positive tumor volume was quantified semiautomatically. Results: In total, 85 CT-based CHAARTED LVD and 20 CT-based CHAARTED HVD patients were included. A PSMA tumor volume of about 40 cm(3) was the optimal cutoff between CT-based CHAARTED LVD (nonunifocal) and HVD (non-M1c) (area under the curve, 0.86). Stratification into PET LVD (unifocal or oligometastatic/disseminated < ∼40 cm(3)) and PET HVD (oligometastatic/disseminated ≥ ∼40 cm(3) or M1c) had 13% misalignment with the CHAARTED criteria. Conclusion: PSMA PET criteria with volume quantification deliver comparable LVD/HVD discrimination with additional subgroups for unifocal, oligometastatic, and disseminated disease, critical for guidance of targeted or multimodal therapy.

Simple Summary For patients with advanced prostate cancer, many different treatment options are available. One option is the radioligand therapy with 177Lutetium labelled prostate-specific membrane antigen (Lu-PSMA). This treatment showed good results in previous studies with only some non-severe side effects. This review offers a short overview about the application, current standings and the future perspective of the radioligand therapy with Lu-PSMA. An approval of this therapy is awaited within 2021. Abstract Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option 177Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from 177Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a given fact, and with the newly published results of the VISION trial its approval is only a matter of time. Recently, investigators started to focus on treating prostate cancer patients in earlier disease stages and in combination with other compounds. This review gives a brief overview of the current state and the future perspectives of 177Lu labelled PSMA radioligand therapy.

LBA4 Background: Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains invariably fatal. Prostate-specific membrane antigen (PSMA) is highly expressed in mCRPC lesions. 177Lu-PSMA-617 is a targeted radioligand therapy that delivers ß-particle radiation to PSMA-expressing cells and surrounding microenvironment. Method: VISION was an international, randomized, open-label phase III study evaluating 177Lu-PSMA-617 in men with PSMA-positive mCRPC previously treated with next-generation androgen receptor signaling inhibition and 1–2 taxane regimens. PSMA positivity (threshold greater than liver) was determined by central review of 68Ga-PSMA-11 scans. Patients were randomized 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks x 6 cycles) plus standard of care (SOC) versus SOC alone. SOC was investigator determined but excluded cytotoxic chemotherapy and radium-223. The alternate primary endpoints were radiographic progression-free survival (rPFS) using PCWG3 criteria by independent central review (ICR) and overall survival (OS). Under the null hypothesis, median rPFS was assumed to be 4 months and OS 10 months for 177Lu-PSMA-617 + SOC for a hazard ratio (HR) of 1.00. Under the alternative hypothesis, median rPFS was assumed to be 6 months for a HR of 0.67 and median OS was assumed to be 13.7 months for a HR of 0.7306. Key secondary endpoints were objective response rate (ORR; RECIST v1.1), disease control rate (DCR), and time to first symptomatic skeletal event (SSE). Results: Between 4 June 2018 and 23 October 2019, 831 of 1179 screened patients were randomized 2:1 to receive 177Lu-PSMA-617 + SOC (n = 551) or SOC only (n = 280). Median study follow-up was 20.9 months at the data cut-off (27 January 2021). Treatment groups were balanced in terms of demographics and baseline characteristics. 177Lu-PSMA-617 + SOC significantly improved rPFS versus SOC alone (median rPFS, 8.7 vs 3.4 months; HR, 0.40 [99.2% CI: 0.29, 0.57]; p < 0.001, one-sided). The alternate primary endpoint of OS was also significantly improved versus SOC alone (median OS, 15.3 vs 11.3 months; HR, 0.62 [95% CI: 0.52, 0.74]; p < 0.001, one-sided). All key secondary endpoints were statistically significant between the treatment arms in favor of 177Lu-PSMA-617 + SOC, including ICR-determined ORR (29.8% vs 1.7%), ICR-determined DCR (89.0% vs 66.7%) and time to first SSE (median time, 11.5 vs 6.8 months; HR, 0.50). While a higher rate of high-grade treatment-emergent adverse events was observed with 177Lu-PSMA-617 (52.7% vs 38.0%), therapy was well tolerated. Conclusions: 177Lu-PSMA-617 plus SOC treatment is a well-tolerated regimen that improves rPFS and prolongs OS compared with SOC alone in men with advanced-stage PSMA-positive mCRPC, supporting its adoption as a standard of care. Clinical trial information: NCT03511664.

Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia.The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials.

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 177Lu 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.

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 [177Lu]-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.

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 177Lu-DOTATATE in progressive meningioma with a special emphasis on state-of-the-art response assessment. Methods Retrospective analysis on PRRT with 177Lu-DOTATATE from 2015 to 2019. Pre- and post-therapy imaging was performed using MRI and 68Ga-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 177Lu-DOTATATE in eight-week intervals. Three patients did not undergo post-therapy 68Ga-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.

Purpose To analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation. Methods In this retrospective single-center cohort, all patients undergoing 99mTc-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 99mTc-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 99mTc-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 99mTc-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.

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 and25% 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 than that of25% (13.9 vs. 4.3 months, p0.001). The median overall survival was 6.1 months.The median survival after RE in hepatic-mCRC depends on the primary tumor side and the preprocedural hepatic tumor burden.

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, 18F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Methods: Ninety-six patients with prostate cancer underwent 18F-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. Results: Of the patients, 90.6% received 18F-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. 18F-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. Conclusion: 18F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases.

Purpose: 68Ga-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 68Ga-PSMA-11 PET/CT with a modified protocol. Methods: In 2017, we used the following scanning protocol for 68Ga-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.

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]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 177Lu-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 [177Lu]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 [177Lu]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. Electronic supplementary material The online version of this article (10.1007/s00259-020-04797-9) contains supplementary material, which is available to authorized users.

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 ([131I]iodine) or limited availability ([124I]iodine). In contrast, [18F]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 [18F]TFB-PET to the clinical reference standard [131I]iodine scintigraphy in patients with recurrent DTC. Methods Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [18F]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 [131I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [18F]FDG-PET-CT was present for 21 patients. Histological verification of [18F]TFB positive findings was available in 4 patients. Results [18F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [131I]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 [131I]iodine scintigraphy was changed: [18F]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 [18F]TFB-PET-CT/MRI with [18F]FDG-PET-CT (64%). Conclusion In the present cohort, [18F]TFB-PET shows higher sensitivity and accuracy than [131I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [18F]TFB-PET with [18F]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 [18F]TFB-PET in recurrent DTC are warranted.

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 68Ga-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.

Patients with metastatic castration-resistant prostate cancer (mCRPC) have limited therapeutic options. Following a theranostics strategy, targeting the prostate-specific membrane antigen (PSMA) by diagnostic and therapeutic radioisotopes is an evolving field in the management of mCRPC. Initial results of PSMA ligands that are conjugated with therapeutic radioisotopes show good efficacy and modest side effects. In this chapter, we present a historical outline and current clinical procedure guidelines for PSMA-targeted therapy regimes.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) 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 due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUVmax). 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 semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with 177Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUVmax, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p

The skeleton is a common site for cancer metastases. Bone metastases are a major cause of morbidity and mortality and associated with pain, pathologic fractures, spinal cord compression, and decreased survival. Various radionuclides have been used for pain therapy. Recently, an α-emitter has been shown to improve overall survival of patients with bone metastases from castration-resistant prostate cancer and was approved as a therapeutic agent. The aim of this article is to provide an overview regarding state of the art radionuclide therapy options for bone metastases, with focus on the role of PET imaging in therapy planning.

Purpose: To evaluate factors associated with survival following transarterial 90Y (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&ndash, 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&ndash, 88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume &gt, 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1&ndash, 12.9 months). Due to loss in follow-up, n = 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 (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.

Background We aimed to compare the prognostic value of myocardial perfusion scintigraphy (MPS) and dobutamine stress echocardiography (DSE) in patients with end-stage renal disease (ESRD) without known coronary artery disease. Methods Two-hundred twenty-nine ESRD patients who applied for kidney transplantation at our centre were prospectively evaluated by MPS and DSE. The primary endpoint was a composite of myocardial infarction (MI) or all-cause mortality. The secondary endpoint included MI or coronary revascularization (CR) not triggered by MPS or DSE at baseline. Results MPS detected reversible ischemia in 31 patients (13.5%) and fixed perfusion defects in 13 (5.7%) patients. DSE discovered stress-induced wall motion abnormalities (WMAs) in 28 (12.2%) and at rest in 18 (7.9%) patients. MPS and DSE results agreed in 85.6% regarding reversible defects (κ = 0.358; P < .001) and in 90.8% regarding fixed defects (κ = 0.275; P < .001). Coronary angiography detected relevant stenosis > 50% in only 15 of 38 patients (39.5%) with pathological findings in MPS and/or DSE. At a median follow-up of 8 years and 10 months, the primary endpoint occurred in 70 patients (30.6%) and the secondary endpoint in 24 patients (10.5%). The adjusted Cox hazard ratios (HRs) for the primary endpoint were 1.77 (95% CI 1.02-3.08; P = .043) for perfusion defects in MPS and 1.36 (95% CI 0.78-2.37; P = ns) for WMA in DSE. The secondary endpoint was significantly correlated with the findings of both modalities, MPS (HR 3.21; 95% CI 1.35-7.61; P = .008) and DSE (HR 2.67; 95% CI 1.15-6.20; P = .022). Conclusion Perfusion defects in MPS are a stronger determinant of all-cause mortality, MI and the need for future CR compared with WMAs in DSE. Given the complementary functional information provided by MPS vs DSE, results are sometimes contradictory, which may indicate differences in the underlying pathophysiology.

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.

PURPOSE: The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially 68Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). 18F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced 18F-PSMA-1007 in patients with recurrent PCa. METHODS: This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq 18F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a 18F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level. RESULTS: Of the 100 patients, 95 (95%) showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04-41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5-10). The majority of patients (70) with a GS available had a score in the range 7-9. The rate of pathological scans in these patients was 93% (65/70). The median SUVmax values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and >2.0 ng/ml, respectively. The median SUVmax in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups. CONCLUSION: 18F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological 18F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients. KEYWORDS: Biochemical relapse; PSMA-1007; Prostate cancer

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is 68Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity, 18F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel 18F-labelled ligand PSMA-1007 at two different time points. This retrospective analysis included 40 consecutive patients (mean age 68.7 ± 8.1 years) referred for PSMA PET/CT. 18F-PSMA-1007 PET/CT was performed for localization of biochemical relapse, primary staging or therapy follow-up. Circular regions of interest were placed on representative slices of the liver, spleen, kidney, abdominal aortic blood pool, bone marrow (fourth lumbar vertebral body), urinary bladder and gluteus muscle at 60 and 120 min after injection. In malignant lesions the maximum standardized uptake (SUVmax) was measured within volumes of interest at both time points. All SUVs at 60 min were compared with those at 120 min after injection. The activity in the blood pool, urinary bladder and gluteus muscle was very low and decreased significantly over time (P

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

// Birthe Heitkotter 1, * , Konrad Steinestel 2, * , Marcel Trautmann 1 , Inga Grunewald 1 , Peter Barth 1 , Heidrun Gevensleben 3 , Martin Bogemann 4 , Eva Wardelmann 1 , Wolfgang Hartmann 1 , Kambiz Rahbar 5 and Sebastian Huss 1 1 Gerhard Domagk Institute of Pathology, University of Munster, Munster, Germany 2 Institute of Pathology, Military Hospital Ulm, Ulm, Germany 3 Institute of Pathology, Neuss, Germany 4 Department of Urology, University Hospital Munster, University of Munster, Munster, Germany 5 Department of Nuclear Medicine, University Hospital Munster, Munster, Germany * These authors contributed equally to this work Correspondence to: Sebastian Huss, email: sebastian.huss@ukmuenster.de Keywords: PSMA; thyroid cancer; tumor neoangiogenesis; prostate cancer Received: July 26, 2017 Accepted: November 15, 2017 Published: January 04, 2018 ABSTRACT Aim: PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods: Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining. Results: PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors ( p = 0.021). However, one case with a strong expression in follicular adenoma was identified. Conclusions: We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.

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.

Aim of this research is to propose a wavelet-fractal model for detection of geochemical anomaly based on a modified Morlet Wavelet Kernel (MMWK). This study was carried out for detection of lithium anomalies regarding stream sediment samples. Major Li anomalies commence from 51.1 ppm obtained by the wavelet-fractal modeling based on Decomposed Wavelet Transformation (DWT) using a conventional Morlet wavelet. A modified kernel for the Morlet wavelet was utilized for separation of the Li anomalies. The MMWK benefits from the use of L1 norm (instead of L2) which consequently provides more robustness and resistance to outliers for stream sediment data. Results derived via the modified Morlet kernel-fractal modeling show that there are principal lithium anomalies with Li ≥ 55.2 ppm. In addition, staged factor analysis was used and Li was placed with Rb, Cs and F in F2-2. Then, the F2-2 main anomalies commence from 2.7 and 2.9 using the conventional Morlet and MMWK, respectively. Subsequently, both methods were compared by a log-ratio matrix with an Overall Accuracy (OA) due to rock samples retaken from these anomalies. These rock samples were classified using a Concentration-Number (C-N) fractal model and high intensive anomalous samples with Li ≥ 126 ppm. This correlation indicated that the OA between the main obtained anomalies by the MMWK and the rock samples are higher than conventional Morlet-fractal modeling.

Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA. Seventy-one patients (median age: 72 years; range 44–87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0.543 GBq) every 8 weeks. Response was evaluated using serum PSA levels and a PSA decline ≥50% was considered as biochemical response. Additionally, any PSA decline after the first cycle was evaluated for further therapy effects after the second and third cycle. A total of 213 cycles were performed in 71 patients. Data for response and adverse events were available for all patients. A PSA decline ≥50% and some PSA decline occurred in 56% and 66% of the patients. Of 30 patients with a PSA response after the first cycle, 28 remained responders and 12/41 of non-responders responded to further therapy cycles. RLT with Lu-177-PSMA-617 shows respectable response rates. In this retrospective analysis, a relevant number of patients showed a delayed response, even if they did not respond to the first cycle of the therapy.

BACKGROUND Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC.

Die Bildgebung spielt eine wichtige Rolle bei der Auswahl derjenigen Patienten mit metastasiertem, kastrastionsrefraktärem Prostatakarzinom, die für eine 223Ra-Dichlorid-Therapie von Knochenmetastasen geeignet sind. Das Ziel dieser Studie war zu untersuchen, ob eine zusätzliche 68Ga-PSMA-PET einen inkrementellen Nutzen gegenüber der konventionellen Bildgebung bei der Auswahl geeigneter Patienten für diese Therapie aufweist.Bei 27 konsekutiv für eine 223Ra- Dichlorid-Therapie vorgestellten Patienten wurde eine zusätzliche 68Ga-PSMA-PET/CT durchgeführt. Die Tracerverteilung wurde systematisch ausgewertet in Hinblick auf die Detektion von viszeralen Metastasen und von ossären Metastasen ohne adäquate Speicherung in der Skelettszintigraphie.Zusätzliche viszerale Metastasen wurden mittels 68Ga-PSMA-PET bei 4 Patienten (15 %) detektiert (3 Leber, 1 Nebenniere), wobei in der Folge das therapeutische Vorgehen bei 2 der 4 Patienten geändert wurde. Mit der PET wurde eine ausgedehntere Knochenmetastasierung im Vergleich zur Skelettszintigraphie bei 9 Patienten (33 %) nachgewiesen. Bei dreien dieser Patienten war der “Mismatch” ausgedehnt genug, um die Durchführung der 223Ra-Dichlorid-Therapie in Frage zu stellen.Die zusätzliche Durchführung einer 68Ga-PSMA-PET als Torwächter zwischen konventioneller Bildgebung und der 223Ra-Dichlorid-Therapie kann wichtige zusätzliche Informationen liefern über das Vorliegen von viszeralen Metastasen und von ossären Tumormanifestationen ohne adäquaten Knochenstoffwechsel. Dieses kann bei einer signifikanten Zahl von Patienten zu einer Änderung des therapeutischen Managements führen und sollte in zukünftigen klinischen Studien berücksichtigt werden.

177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using inhibitors of PSMA is a novel therapeutic option in patients with metastatic castration-resistant prostate cancer. The current literature suggests that this therapy is well tolerated and effective. On the basis of clinical need and current evidence, the therapy is being implemented in a growing number of centers worldwide. Here, we review important aspects of 177Lu-PSMA RLT, including patient stratification, the therapy protocol, concomitant medication, and follow-up, to inform medical staff involved in the RLT and care of patients with metastatic castration-resistant prostate cancer.