¹⁷⁷Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of ¹⁷⁷Lu-PSMA-617 in a large cohort of patients. Methods: One hundred forty-five patients (median age, 73 y; range, 43–88 y) with mCRPC were treated with ¹⁷⁷Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1–4 therapy cycles and an activity range of 2–8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician’s report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2–30 wk). Nineteen patients died during the observation period. Grade 3–4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of ¹⁷⁷Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

In the diagnostic algorithm of cardiac tumors, the noninvasive determination of malignancy and metastatic spread is of major interest to stratify patients and to select and monitor therapies. In the diagnostic work-up, morphologic imaging modalities such as echocardiography or magnetic resonance tomography offer information on, for example, size, invasiveness, and vascularization. However, preoperative assessment of malignancy may be unsatisfactory. The aim of this study was to evaluate the diagnostic value of ¹⁸F-FDG PET and the incremental diagnostic value of an optimized CT score in this clinical scenario. Methods: ¹⁸F-FDG PET/CT scans (whole-body imaging with low-dose CT) of 24 consecutive patients with newly diagnosed cardiac tumors were analyzed (11 men, 13 women; mean age ± SD, 59 ± 13 y). The maximum standardized uptake values (SUV_max) of the tumors were measured. Patients were divided into 2 groups: benign cardiac tumors (n = 7) and malignant cardiac tumors (n = 17) (cardiac primaries [n = 8] and metastases [n = 9]). SUV_max was compared between the 2 groups. Results were compared with contrast-enhanced CT, using standardized criteria of malignancy. Histology served as ground truth. Results: Mean SUV_max was 2.8 ± 0.6 in benign cardiac tumors and significantly higher both in malignant primary and in secondary cardiac tumors (8.0 ± 2.1 and 10.8 ± 4.9, P < 0.01). Malignancy was determined with a sensitivity of 100% and specificity of 86% (accuracy, 96%), after a cutoff with high sensitivity (SUV_max of 3.5) was chosen to avoid false-negatives. Morphologic imaging reached a sensitivity of 82% and a specificity of 86% (accuracy, 83%). Both false-positive and false-negative decisions in morphology could be corrected in all but 1 case using a metabolic threshold with an SUV_max of 3.5. In addition, extracardiac tumor manifestations were detected in 4 patients by whole-body ¹⁸F-FDG PET/CT. Conclusion: ¹⁸F-FDG PET/CT can aid the noninvasive preoperative determination of malignancy and may be helpful in detecting metastases of malignant cardiac tumors.

Radioligand therapy (RLT) with 177Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments. RLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). 68Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5–853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1–6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes. Eight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4). Our initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.

Background: Radiolabelled prostate specific membrane antigen (PSMA) ligands represent a true theranostics concept for diagnosis and therapy of relapsed and metastatic prostate cancer patients. The aim of this study was to evaluate response and tolerability of a single dose of ¹⁷⁷Lutetium-PSMA-617 (Lu-PSMA) in a large cohort of patients with metastatic castration resistant prostate cancer (mCRPC). Methods: The data of 82 consecutive patients (median age: 73 years, range: 43-87) with metastatic castration resistant prostate cancer who received a single dose of Lu-PSMA (mean: 5.9±0.5 GBq) were retrospectively analyzed. Data was collected at baseline and 8 weeks after therapy. ⁶⁸Ga-PSMA-11 PET/CT was performed in all patients to verify sufficient PSMA expression. Bone, lymph node, liver and lung metastases were present in 99%, 65%, 17% and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data and prostate specific antigen (PSA) value at baseline and 8 weeks after therapy application. Results: A total of six patients died and two patients dropped out not willing to continue therapy and follow-up. Complete dataset of 74 patients were available for analysis. 47 (64%) of the patients showed a PSA-Decline, of these 23 (31%) had a PSA decline > 50%, 35 (47%) had a stable disease with a PSA decline from <50% to an increase 25%. There were no significant changes indicative of toxicity in hemoglobin, white blood cells, creatinine and tubular extraction rates. There was a significant but mild decrease of platelets with a median value still within the normal range. Conclusion: This retrospective multicenter analysis suggests that radioligand therapy with Lu-PSMA is safe, well tolerated and shows considerable response in PSA values. Therefore, it offers an additional therapeutic option for patients with mCRPC. This data may justify further prospective randomized studies to evaluate and prove the clinical benefit in survival and quality of life.

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.

Background Despite progress in treatment of metastatic castration-resistant prostate cancer (mCRPC), new approaches are urgently needed. Recently theranostic concepts using radiolabeled ligands of the prostate-specific membrane antigen (PSMA) have been developed for diagnostics and therapy of patients with advanced mCRPC. The aim of this study was to evaluate tumor response, adverse effects, and survival in patients undergoing radioligand therapy with ¹⁷⁷Lu-PSMA-617. Methods Fifty therapies using ¹⁷⁷Lu-PSMA-617 were performed in 28 consecutive patients with mCRPC and exhausted conventional therapeutic options (median age, 73.4 years; range, 45–87 years). Data were retrospectively analyzed with focus on response, safety, and survival. The median overall survival was compared with that of a recent historical patient cohort treated with best supportive care prior to availability of ¹⁷⁷Lu-PSMA-617. Results Any PSA decline occurred in 59% and 75% of patients after 1 and 2 therapies. Moreover, a PSA decline of 50% or greater occurred in 32% and 50%. Therapies were well tolerated. Hematologic and renal parameters changed insignificantly; permanent xerostomia or other safety-related toxicity did not occur. The estimated median survival was 29.4 weeks, significantly longer than survival in the historical best supportive care group (19.7 weeks [hazard ratio, 0.44; 95% confidence interval, 0.20–0.95]; P = 0.031). Conclusions Results from 50 therapies show that radioligand therapy with ¹⁷⁷Lu-PSMA-617 is effective and well tolerated and seems to increase overall survival. A future randomized controlled prospective study will be necessary to confirm these results.