PSMA PET/CT has transformed the detection of nodal recurrence after radical prostatectomy, yet real-world evidence on long-term outcomes of PSMA PET/CT-guided salvage elective nodal radiotherapy (ENRT) remains limited. This study evaluated oncological outcomes of PSMA PET/CT-guided salvage ENRT in a bi-institutional cohort with extended follow-up. We retrospectively analysed 179 patients who received PSMA PET/CT-based ENRT for nodal recurrence after radical prostatectomy at two tertiary centres between 2014 and 2024. Patients with pelvic and/or paraaortic lymph node metastases were included. The primary endpoint was metastasis-free survival (MFS); secondary endpoints included biochemical progression-free survival (BPFS) and overall survival (OS). Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were assessed using Cox regression analysis. Of the 179 patients, 104 (58.1

The identification of metastatic disease in patients with biochemical failure of prostate cancer (PCa) after radical prostatectomy (RP) determines subsequent treatment management. Our objectives were (i) to assess the prevalence of metastatic PCa in patients with biochemical failure following RP and PSA levels ≤ 1 ng/mL, as detected by 18F-PSMA-1007 PET/CT (PSMA-PET), and (ii) to identify predictors of metastatic disease. Fifty-five patients with biochemical recurrence (BCR, n = 47) or persistent disease (n = 8) following RP as their primary and only prior treatment were retrospectively included if presenting with PSA levels ≤ 1 ng/mL. Patients who received any other anticancer treatment were excluded. PSMA-PET findings were categorized as either local recurrence (i.e., prostatic fossa and seminal vesicles) or metastases. Predictors of PSMA-PET positivity were assessed with univariate and multivariate regression analyses both in the whole sample and in two subgroups defined according to PSA levels (Group A = PSA < 0.5 ng/mL; Group B = PSA between 0.5 and 1 ng/mL). Median PSA at the time of PET/CT was 0.37 ng/mL (range: 0.13–1.0). PSMA-PET was positive in 22/55 (40

The management of treatment-refractory meningioma in patients with previous surgical resection and radiation therapy remains challenging due to the lack of effective systemic treatment options. Therefore, novel therapeutic applications, such as peptide receptor radionuclide therapy (PRRT) targeting somatostatin receptors, may offer a promising therapeutic strategy. We aimed to assess the lesion-based tumour-absorbed dose and efficacy of PRRT with [90Y]Y-DOTATOC in patients with treatment-refractory meningioma. In this study, 10 patients with therapy-refractory meningioma were retrospectively included. All patients received systemic [90Y]Y-DOTATOC therapy following prior surgical resection and radiation therapy. In total, 21 lesions were assessed morphologically by contrast-enhanced MRI and [68Ga]Ga-DOTATOC PET/CT both before and after therapy. All patients underwent dosimetry with [111In]In-DOTATOC prior to [90Y]Y-DOTATOC therapy. Treatment response was evaluated according to RANO bidimensional and volumetric criteria. Overall survival (OS) was defined from the first PRRT cycle until death. The median cumulative activity administered per patient was 3804 MBq (IQR, 3140–4050 MBq), with a median of 3 cycles (range: 1–7). On lesion-based analysis following PRRT, response assessment was available in 19/21 (91.5

No specific statements regarding the use of 2-[18F]fluoro-2-deoxy-D-glucose positron-emission tomography/computed tomography ([18F]FDG PET) in the context of immunotherapy are made in current international oncological guidelines for the management of the two cancer types for which the largest body of evidence has been generated, such as melanoma and non-small cell lung cancer (NSCLC). However, practice guidelines released jointly by leading nuclear medicine societies recommended the use of [18F]FDG PET alongside computed tomography (CT) before immunotherapy initiation, for early response assessment, and in patients considered for therapy discontinuation. In the present paper we critically reviewed the available literature on the comparison between [18F]FDG PET and CT for response assessment in patients undergoing immunotherapy, with the aim to identify where metabolic imaging holds the most significant promise. In early response assessment, where an accurate discrimination between pseudoprogression and true tumor progression is necessary, [18F]FDG PET is of limited value. In contrast, there are at least two clinical scenarios in which [18F]FDG PET could outperform CT because of its high negative predictive value, that are the evaluation of response to neoadjuvant immunotherapy or before therapy discontinuation. We emphasized that the generation of robust evidence is necessary before clinical implementation, as it ensures the optimal allocation of resources and better patient care.

Purpose To develop and validate LION (Lesion Identification in Oncological Nuclear imaging), an open-source PET-only tumor segmentation pipeline for [ 18 F]FDG and PSMA-targeted PET/CT, and to investigate how training data characteristics influence segmentation performance. Materials and Methods In this retrospective multicenter study, 5,209 [ 18 F]FDG PET/CT scans spanning 19 disease types and 2,046 PSMA-targeted PET/CT scans were used to train PET-only segmentation models. Tumor segmentation incorporated organs with physiological uptake as auxiliary classes to enable PET-only inference. Tumor Occurrence Maps (TOMs) quantified tumor spatial diversity across the training data. For [ 18 F]FDG, disease-specific and mixed-disease models trained on progressively larger subsets were compared to test whether increasing spatial diversity improves generalization. Scanner-related domain shift was analyzed using DINOv2 embeddings. Models were evaluated on multicenter holdout cohorts (616 [ 18 F]FDG across 4 diseases; 443 PSMA-targeted prostate cancer scans) and compared with three open-source tools. Results Organ context improved median Dice from 0.62 to 0.71 for [ 18 F]FDG and from 0.75 to 0.83 for PSMA. Spatial diversity measured by TOMs was strongly associated with Dice (Spearman ρ = 0.87, P < 0.001). A mixed-disease model trained on 500 patients matched the performance of a lymphoma specialist model trained on 3,031 cases. DINOv2 embeddings revealed scanner-induced domain shift, between same-disease cohorts. LION achieved median Dice scores of 0.71 ([ 18 F]FDG) and 0.85 (PSMA) and outperformed other open-source approaches on common holdout patients. Conclusion LION enables PET-only automated segmentation for [ 18 F]FDG and PSMA-targeted PET. Training data composition, particularly spatial diversity quantified by TOMs, was strongly associated with segmentation performance.

Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for neuroendocrine tumors (NETs), enabling targeted radiation delivery via radiolabeled peptides. Small cell lung cancer (SCLC) remains a major therapeutic challenge due to its aggressive nature and poor prognosis. Despite advances, relapse rates are high and effective therapies are limited. We previously demonstrated the diagnostic potential of the cholecystokinin-2 receptor (CCK2R)-targeting minigastrin analog [68Ga]Ga-DOTA-MGS5 in PET/CT imaging of different NETs. Building on this, we developed and evaluated [177Lu]Lu-DOTA-MGS5 as a therapeutic PRRT agent. Methods: Preclinical studies investigating the receptor-mediated cellular internalization and intracellular distribution over time in A431 cells with and without CCK2R expression were performed using the fluorescent tracer ATTO-488-MGS5. Short- and long-term cytotoxic effects of [177Lu]Lu-DOTA-MGS5 were evaluated on the same cell line using trypan blue exclusion and clonogenic survival assays. CCK2R expression was assessed by immunohistochemistry in 42 SCLC tissue specimens. In addition, the first PRRT with [177Lu]Lu-DOTA-MGS5 was conducted in a patient with extensive disease SCLC (ED-SCLC) after confirming CCK2R-positive uptake in [68Ga]Ga-DOTA-MGS5 PET/CT. Results: Rapid binding and internalization into A431-CCK2R cells, with progressive accumulation in intracellular compartments, was observed for ATTO-488-MGS5. Short-term irradiation effects of [177Lu]Lu-DOTA-MGS5 were comparable for 4 h and 24 h incubation and were between the effects obtained with 2 and 4 Gy of external beam radiotherapy (EBRT). Clonogenic survival of A431-CCK2R cells incubated with increasing activity of [177Lu]Lu-DOTA-MGS5 decreased in a dose-dependent manner. Immunohistochemistry on SCLC specimens confirmed moderate to high CCK2R expression in 16 out of 42 SCLC samples. In the first patient with SCLC treated with four cycles of [177Lu]Lu-DOTA-MGS5 with a total activity of 17.2 GBq, an improvement in clinical symptoms was observed. Conclusions: The preclinical and clinical results confirm the feasibility of [177Lu]Lu-DOTA-MGS5 PRRT in patients with SCLC and support further clinical studies investigating the therapeutic value and clinical applicability of this new CCK2R-targeted theranostic approach in larger patient cohorts.

Peptide receptor radionuclide therapy (PRRT) has established itself as a pivotal component in the management of advanced, somatostatin receptor (SSTR)-positive neuroendocrine tumours (NETs). The NETTER-1 phase III trial demonstrated that [177Lu]Lu-DOTATATE significantly prolongs progression-free survival (PFS) and improves quality of life in patients with midgut NETs refractory to somatostatin analogues, leading to regulatory approval by both EMA (2017) and FDA (2018). The recent NETTER-2 phase III trial further extended these findings by supporting the first-line use of PRRT in Grade 2 and 3 gastroentero-pancreatic (GEP)-NETs (Ki-67 ≥ 10 ≤ 55

Rationale: Rechallenge peptide receptor radionuclide therapy (PRRT) is a valid therapeutic option for patients with advanced/metastatic neuroendocrine tumors (NETs) who previously benefited from initial PRRT. In this context, [18F]FDG PET may serve as a prognostic marker. This multicenter 10-year survival study aims to evaluate the prognostic implications of [18F]FDG PET and PRRT-induced changes in NET patients undergoing rechallenge PRRT. Methods: This retrospective multicenter study included 100 patients (median age: 54 years, range: 29-83) treated with rechallenge PRRT. All patients underwent [68Ga]Ga-DOTA-TOC/TATE/NOC and [18F]FDG PET/CT prior to the first PRRT period, 3-4 months after PRRT, and every 6-9 months thereafter. Metabolic status and its changes (no change vs. FDG+/FDG- vs. FDG-/FDG+) before the first PRRT period and at each restaging were recorded and correlated to baseline characteristics, time to progression (TTP), and overall survival (OS). Results: In 43 out of 100 patients, the primary tumor site was the pancreas; the liver was involved in more than 90% of patients. Biopsies revealed G1 NET in 16%, G2 NET in 66%, and G3 NET in 18% of cases. Before the first PRRT period, 50% of patients were FDG-positive. Following the first PRRT period, 27 patients exhibited a change in metabolic status: 20 converted to FDG-negative, whereas 7 became FDG-positive. After the second PRRT period, metabolic status changed in 41 patients, with 25 converting to FDG-negative and 16 to FDG-positive. Metabolic status after the first period was significantly correlated with NET grade (p = 0.009). The correlation persisted also after rechallenge (p < 0.001), suggesting that FDG positivity increased progressively in G3 NET patients (p = 0.020). The presence of bone metastases statistically correlated with FDG positivity before (p < 0.001) and after (p = 0.001) the first PRRT period. Multivariate Cox regression analysis revealed NET G3 and FDG status after the first PRRT course as independent factors for shorter TTP. After a median follow-up time of 117.6 months (range: 38.4-180 months), 37 patients had died. Multivariate Cox regression analysis revealed FDG positivity after the first (p < 0.001) and second (p < 0.001) periods of PRRT as independent predictors of poor OS. Conclusions: Assessing [18F]FDG status before PRRT and during follow-up after treatment enables prediction of TTP and OS, even in patients considered for rechallenge PRRT. Standardizing the use of dual-tracer imaging in patients receiving PRRT seems a valuable approach to improve clinical decision-making in NET patients.

Little is known about predictors of response to radionuclide therapy with PSMA-ligands in patients with [18F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed the correlation between baseline characteristics, including dual tracer PET parameters, and response to [177Lu]Lu-PSMA-I T in a cohort of patients with [18F]FDG-positive mCRPC. Prognostic factors related to progression-free survival (PFS) and overall survival (OS) were also investigated. mCRPC patients who underwent [68Ga]Ga-PSMA-11 and [18F]FDG PET/CT prior to [177Lu]Lu-PSMA-I T were retrospectively evaluated. Only [18F]FDG-positive patients were included in the analysis. A semi-automatic segmentation tool was applied to measure the whole-body maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion uptake (TLU) on both PET/CTs. PSA response was defined as ≥ 30

Fever of unknown origin (FUO) presents a significant diagnostic challenge because of its wide range of potential causes. The role of [18F]FDG PET/CT in this complex clinical scenario is not yet fully understood. This multicenter retrospective observational study aimed to investigate the diagnostic value and clinical impact of [18F]FDG PET/CT in patients with FUO and to identify specific factors linked to a positive [18F]FDG PET/CT scan. Methods: We retrospectively included 929 patients from 12 centers who underwent [18F]FDG PET/CT for FUO. The final diagnosis for each patient was established on the basis of laboratory, imaging, histopathologic or pathologic examinations, and at least 6 mo of clinical follow-up data. Final diagnoses were classified into 4 categories: infectious diseases, noninfectious inflammatory diseases, malignancies, and unknown causes (no diagnosis). Moreover, the impact of [18F]FDG PET/CT on clinical management, as well as its association with clinical, epidemiologic, and biochemical parameters were analyzed. Results: The final diagnoses included infectious diseases in 332 patients (36%), noninfectious inflammatory diseases in 281 (30%), and malignancies in 103 (11%). The cause of FUO remained undiagnosed in 213 patients (23%). [18F]FDG PET/CT scans had positive results for 549 (59%) patients and negative for the remaining 380 patients. The overall [18F]FDG PET/CT sensitivity was 72% (95% CI, 69%-75%), specificity was 85% (95% CI, 79%-89%), positive predictive value was 94% (95% CI, 92%-96%), negative predictive value was 47% (95% CI, 44%-51%), and accuracy was 75% (95% CI, 72%-78%). Predictive markers for a positive PET/CT scan were high C-reactive protein, high erythrocyte sedimentation rate, high neutrophil-to-lymphocyte ratio, the presence of fever at the time of PET, and short duration of prior antibiotic therapy. Moreover, [18F]FDG PET/CT findings directly influenced the clinical management of approximately 75% of patients. Conclusion: [18F]FDG PET/CT is a high-yield diagnostic tool that directly influenced clinical management of approximately 75% of patients with FUO, with optimal performance in patients with elevated inflammatory markers, fever at the time of imaging, and limited prior antibiotic use.

Recent data demonstrate that one possibility for increasing Peptide Receptor Radionuclide Therapy (PRRT) results lies in the combination of PRRT with chemotherapy. This study aimed to evaluate response and outcome in [18F]FDG-positive metastatic neuroendocrine tumor (mNET) patients treated with PRRT alone or in combination with temozolomide (TEM) plus/minus capecitabine (CAP). All mNET patients presented with [18F]FDG-positive disease prior to treatment (or retreatment) with PRRT alone or in combination with chemotherapy were retrospectively included in this single-center study. Patients received [177Lu]Lu-DOTATATE with an activity of 7.4 GBq alone or combined with TEM (200 mg/kg/5d) plus/minus CAP (1500 mg/kg/14d). Contrast-enhancement CT (ceCT), [68Ga]Ga-DOTATOC and [18F]FDG PET/CT studies were performed at baseline, after treatment, and every 6 months thereafter. Overall response rate (ORR) and disease control rate (DCR) were calculated for each group. Survival analysis was performed using the Kaplan-Meier method. Adverse events were collected and classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A total of 24 patients were included in the final analysis. Group 1 received PRRT with [177Lu]Lu-DOTATATE alone (n = 10), group 2 received [177Lu]Lu-DOTATATE plus TEM (n = 7), and group 3 received [177Lu]Lu-DOTATATE plus CAPTEM (n = 7). There were no differences between groups in terms of clinicopathological features before treatment. The pancreas was the primary tumor site in 58

Several exploratory studies have demonstrated the feasibility of cholecystokinin-2 receptor (CCK2R) targeting in patients with medullary thyroid carcinoma (MTC) and other neuroendocrine tumors (NETs). We report the results of a prospective phase I/IIA pilot study (clinicaltrials.gov NCT06155994) conducted at our center with the 68Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH2 (68Ga-DOTA-MGS5). Methods: Six patients with advanced MTC and 6 patients with gastroenteropancreatic and bronchopulmonary NETs confirmed by previous PET/CT imaging with other PET tracers received a single dose of 180 MBq of 68Ga-DOTA-MGS5. The first 6 patients enrolled in the study were included in the dosimetry evaluation, and safety was assessed in all 12 patients. PET/CT imaging was performed at different time points after injection to perform dosimetric calculations and to determine the optimal imaging time window. In addition, blood and urine samples were collected for pharmacokinetic assessments. Results: The administration of 68Ga-DOTA-MGS5 was well tolerated, with minor adverse drug reactions occurring only in 3 patients. 68Ga-DOTA-MGS5 was cleared rapidly from the blood, with less than 21% of the injected activity present in blood 215 ± 10 min after injection. Tracer elimination occurred mainly through the kidneys, with a cumulative urinary excretion greater than 40% 3 h after injection. A high percentage of intact radiopeptide was confirmed in plasma. The highest absorbed dose was found for the urinary bladder wall, the stomach wall, and the kidneys, with an effective dose of 0.023 ± 0.007 mSv/MBq. The time points of 1 and 2 h after injection proved to be optimal for PET/CT imaging. In the 6 patients included in the dosimetry evaluation, local metastasis was confirmed in 2 patients with advanced MTC, whereas only 1 of 4 patients with gastroenteropancreatic NETs was positive in 68Ga-DOTA-MGS5 PET/CT. Conclusion: Besides confirming the safety of administration, within the phase I part of the prospective clinical trial, an acceptable effective whole-body dose, an overall favorable biodistribution, and the feasibility of cholecystokinin-2 receptor imaging could be shown for 68Ga-DOTA-MGS5.

Conventional systemic therapies are valuable options in prostate cancer (PCa); however, such treatments can determine adverse events and toxicity. The observed improvement in overall survival, coupled with PSA reduction and a favorable safety profile in the post-taxane castration-resistant PCa (CRPC) setting has prompted the consideration of PSMA-based radioligand therapy (RLT) earlier in the treatment sequence. In this review, we will describe the literature and ongoing clinical trials regarding the use of PSMA-based RLT in hormone-sensitive PCa (HSPC) including the neoadjuvant, de-novo/synchronous metastatic, adjuvant, and early BCR settings. We performed a systematic literature search on the PubMed/MEDLINE/EMBASE and clinicaltrials.gov databases for studies and protocols assessing the role of PSMA-based RLT in HSPC. The literature search yielded 140 results. After screening titles and abstracts and applying inclusion and exclusion criteria, we selected 25 papers showing the potentialities of earlier RLT in HSPC, with several ongoing trials. Early use of PSMA-based RLT holds significant potential in HSPC patients from the neoadjuvant to the BCR setting. In these stages, the lower tumor burden, more frequent exclusive nodal involvement, and higher organ reserve may improve treatment efficacy and allow for treatment combinations while maintaining a less toxic profile.

First isolated by Brazeau et al. in 1972, somatostatin (SST) is a neuropeptide known for regulating various signaling pathways through its specific cell surface receptors. Somatostatin receptors (SSTRs) comprise a family of five G protein-coupled receptors that are widely distributed across the human body and are expressed by various tumor types. The growing understanding of their clinical potential led to the introduction of both cold and radiolabeled somatostatin analogs (SSAs), which have revolutionized the management of several cancers, especially neuroendocrine tumors. As a direct consequence, advances in peptide receptor radionuclide therapy (PRRT) over the last 30 years led to the approval of 177Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Theoretically, any cancer patients whose tumors express SSTR, as demonstrated in vivo through SSTR-based molecular imaging, could be candidates for PRRT, especially those with limited treatment options. However, evidence on the efficacy of PRRT in non-GEPNET SSTR-expressing tumors is limited, and mainly derived from small retrospective studies. Given the limited therapeutic options for advanced/metastatic patients, there is a clear need for randomized trials to formally approve PRRT with SSAs for patients who may benefit from this treatment, particularly in certain types of neuroendocrine neoplasms such as lung carcinoids, paragangliomas, and meningiomas, where high rates of disease control (up to 80%) can be achieved. In addition, emerging evidence supports the potential of combination therapies, alpha emitters, and non-SSTR-based radionuclide therapy in tumors beyond GEPNET. This review aims to provide a comprehensive overview of PRRT's role in cancers beyond GEPNET, exploring new possibilities and future directions for most SSTR highly expressing tumors.

Background: Different evidence on the ability of [18F] fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging to assess patients in the vegetative state (VS) or unresponsive wakefulness syndrome (UWS) has been reported. Therefore, this systematic review aimed to synthesize the existing literature on this topic. Methods: A wide literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles investigating the role of [18F]FDG PET imaging in the assessment of VS/UWS. Results: Thirty-seven studies were included in the review, and the main fields of application of this imaging modality in these patients were the evaluation of hypometabolic patterns, differentiation of disorders of consciousness (DOC), prognostic value, and ability to assess the response to particular stimuli. Conclusions: The possible role of [18F]FDG PET imaging in the assessment of VS/UWS has emerged, in particular in the differential diagnosis of other DOC or prognosis. Some insights into its value in stimulation response and therapy evaluation have also been proposed. Standardization of protocols and larger prospective studies are needed to strengthen these clinical recommendations.

Background/Objectives: [18F]FDG-PET is often used for staging thymic epithelial tumours (TETs). However, its prognostic role remains uncertain. The aim of this present systematic review and meta-analysis is to assess the prognostic value of baseline [18F]FDG-PET-derived semiquantitative parameters in predicting progression-free survival (PFS) in patients with TETs. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. PubMed, Embase, and Scopus databases were searched up to 30 May 2025. Studies evaluating the prognostic impact of [18F]FDG-PET parameters on PFS in TETs were included. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: Six retrospective studies involving 593 patients were included. Maximum standardized uptake value (SUVmax), analysed as a continuous variable in four studies, significantly predicted worse PFS (HR: 1.18, 95% CI: 1.08–1.29, p < 0.001), with high inter-study heterogeneity (I2 = 79.7%). When dichotomized (two studies), higher SUVmax was associated with significantly poorer PFS (HR: 9.00, 95% CI: 2.93–27.71). Similarly, mean SUV (SUVmean) as a continuous predictor was also significantly associated with impaired PFS (HR: 1.41, 95% CI: 1.25–1.59), but only two studies assessed this parameter. Conversely, metabolic tumour volume (MTV) and total lesion glycolysis (TLG), both assessed as continuous prognosticators, did not show a significant prognostic value. Notably, in both MTV and TLG analyses, two studies contributed a weight of 0%, reflecting limited precision and highlighting the need for larger data. Conclusions: Baseline [18F]FDG-PET parameters such as SUVmax and SUVmean showed a potential prognostic value in patients with TETs. However, these results are based on a limited number of retrospective studies with significant heterogeneity. Prospective multicentre investigations are necessary to confirm the potential role of [18F]FDG-PET for risk stratification in TETs.

The purpose of this study was to evaluate the safety and outcome of rechallenge [177Lu]Lu-PSMA-I T in newly progressed mCRPC patients after response to initial [177Lu]Lu-PSMA radioligand therapy (PRLT). We retrospectively included 18 patients who underwent rechallenge with [177Lu]Lu-PSMA-I T. All patients presented with (i) newly progressed disease after response to initial PRLT; (ii) a [68Ga]Ga-PSMA-11 PET/CT confirming the presence of PSMA-positive metastases; iii) ECOG performance status 0–1. Adverse events were graded according to CTCAE v5.0. Response was assessed by PSA and classified according to PCWG3 recommendations. For patients who underwent restaging with [68Ga]Ga-PSMA-11 PET/CT, imaging response was categorised according to adapted PERCIST v1.0. In patients with discordant [68Ga]Ga-PSMA-11 PET/CT and PSA, other available imaging modalities were evaluated to confirm disease status. Overall survival (OS) was calculated from the first cycle of initial PRLT and rechallenge PRLT, respectively, until last patient contact or death. Patients were initially treated with a median of 5 cycles (range 4–7) and were rechallenged after a median of 9 months (range 3–13). Each patient received a median of 4 (range 2–7) rechallenge cycles (median cumulative activity 26.1 GBq). None of the patients experienced life-threatening G4 adverse events during either treatment period. Grade 3 adverse events included one case of anaemia, one case of thrombocytopenia, and one case of renal failure. In 8/18 patients long-term toxicities were evaluated. Serious toxicities (≥ Grade 3) occurred in 3/8 patients (n = 1 G4 thrombocytopenia, n = 1 G4 renal failure and n = 1 pancytopenia and G4 renal failure). Best PSA50