NETTER-1 trial demonstrated high efficacy and low toxicity of four cycles of Peptide Receptor Radionuclide Therapy (PRRT) in patients with metastasized NET. The present study evaluates the outcome of further PRRT cycles in the so called salvage setting in patients after initial response to four therapy cycles and later progression. Thirty five patients (pat.) (25 male, 10 female, 63 ± 9 years) with progressive, metastasized NET (23 small intestinal, 5 lung, 4 CUP, 1 rectal, 1 gastric and 1 paraganglioma) were included. All patients previously received 4 PRRT cycles with 177Lu-DOTATATE and showed initial response. SPECT based dosimetry was applied to determine kidney and tumor doses. Therapy response was evaluated using 68Ga-DOTATATE PET/CT (with high dose CT), CT alone or MRI (RECIST 1.1), toxicity was defined using CTCAE 5.0 criteria. 99mTc99-MAG3 scintigraphy was used to assess potential renal tubular damage. Progression free survival (PFS) and Overall survival (OS) analysis was performed with the Kaplan-Meier-method. The median PFS after initial PRRT was 33 months (95% CI: 30–36). The mean cumulative dose for including salvage PRRT was 44 GBq (range 33.5–47). One pat. (2.9%) showed grade 3 hematotoxicity. Kidney dosimetry revealed a mean cumulative kidney dose after a median of 6 PRRT cycles of 23.8 Gy. No grade 3 / 4 nephrotoxicity or relevant decrease in renal function was observed. Follow-up imaging was available in 32 patients after salvage therapy. Best response according to RECIST 1.1. was PR in one patient (3.1%), SD in 26 patients (81.3%) and PD in 5 patients (15.6%). PFS after salvage therapy was 6 months (95% CI: 0–16; 8 patients censored). Mean OS after initial PRRT was 105 months (95% CI: 92–119) and 51 months (95% CI: 41–61) after start of salvage therapy. Median OS was not reached within a follow-up of 71 months after initial PRRT and 25 months after start of salvage PRRT, respectively. Salvage therapy with 177Lu-DOTATATE is safe and effective even in patients with extensive previous multimodal therapies during disease progression and represents a feasible and valuable therapy option for progressive NET.

⁹⁰Y radioembolization (selective internal radiation therapy [SIRT]) is a valuable therapeutic option for unresectable hepatic metastases arising from primary colorectal cancer. The present study evaluated the prognostic value of ¹⁸F-FDG PET/CT metabolic parameters for predicting survival after SIRT. Methods: Eighty patients with hepatic metastases of colorectal cancer were treated with SIRT. ¹⁸F-FDG PET/CT was performed at baseline and 3 mo after the treatment. Metabolic volume, total lesion glycolysis, and maximum and peak standardized uptake value (SUV_max and SUV_peak, respectively) according to PET Response Criteria in Solid Tumors (PERCIST 1.0) were obtained from 3 liver lesions in each patient, and the corresponding percentage changes from baseline to follow-up were calculated. Tumor response was defined as more than a 30% decrease in these parameters. Furthermore, response was evaluated in accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Toxicity events and survival were recorded. Results: Overall median survival after SIRT was 60 wk. Responders who had a change in metabolic volume or total lesion glycolysis had significantly longer survival (92 vs. 49 wk [P = 0.006] and 91 vs. 48 wk [P = 0.025], respectively). However, neither RECIST 1.1 criteria nor changes in SUV_peak or SUV_max after treatment predicted outcome (P = 0.086 for RECIST; P = 0.310 for change in SUV_peak; P = 0.155 for change in SUV_max). Conclusion: Changes in metabolic volume and total lesion glycolytic rate as measured by ¹⁸F-FDG PET predicted survival in patients with hepatic metastases from colorectal cancer, whereas changes in SUV_peak or SUV_max and RECIST 1.1 criteria did not predict survival.

PSMA PET/CT visualises prostate cancer residual disease or recurrence at lower PSA levels compared to conventional imaging and results in a change of treatment in a remarkable high number of patients. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival. Thus, it can be hypothesised that PSMA PET/CT-based radiotherapy might improve the prognosis of these patients. One hundred twenty-nine patients underwent PSMA PET/CT due to biochemical persistence (52%) or recurrence (48%) after radical prostatectomy without evidence of distant metastases (February 2014–May 2017) and received PSMA PET/CT-based radiotherapy. Biochemical recurrence free survival (PSA ≤ 0.2 ng/ml) was defined as the study endpoint. Patients with biochemical persistence were significantly more often high-risk patients with significantly shorter time interval before PSMA PET/CT than patients with biochemical recurrence. Patients with biochemical recurrence had significantly more often no evidence of disease or local recurrence only in PSMA PET/CT, whereas patients with biochemical persistence had significantly more often lymph node involvement. Seventy-three patients were started on antiandrogen therapy prior to radiotherapy due to macroscopic disease in PSMA PET/CT. Cumulatively, 70 (66–70.6) Gy was delivered to local macroscopic tumor, 66 (63–66) Gy to the prostate fossa, 61.6 (53.2–66) Gy to PET-positive lymph nodes and 50.4 (45–52.3) Gy to lymphatic pathways. Median PSA after radiotherapy was 0.07 ng/ml with 74% of patients having a PSA ≤ 0.1 ng/ml. After a median follow-up of 20 months, median PSA was 0.07 ng/ml with ongoing antiandrogen therapy in 30 patients. PET-positive patients without antiandrogen therapy at last follow-up (45 patients) had a median PSA of 0.05 ng/ml with 89% of all patients, 94% of patients with biochemical recurrence and 82% of patients with biochemical persistence having a PSA ≤ 0.2 ng/ml. Post-radiotherapy PSA ≤ 0.1 ng/ml and biochemical recurrence vs. persistence were significantly associated with a PSA ≤ 0.2 ng/ml at last follow-up. PSMA PET/CT-based radiotherapy is an effective local salvage treatment option with significant PSA response in patients with biochemical recurrence or persistence after radical prostatectomy leading to deferral of long-term ADT or systemic therapy.

⁶⁸Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (⁶⁸Ga-PSMA PET/CT) offers unprecedented accuracy for staging of primary, persistent or recurrent prostate cancer. Thus, we hypothesized that PSMA PET/CT prior to radiotherapy significantly impacts the radiotherapeutic approach in comparison to the current standard of CT based approach. Methods: Between February 2014 and December 2017, a total of 172 patients received PSMA PET/CT before radiotherapy and were included in this retrospective analysis. Twenty-two (13%) patients were referred for primary definitive radiotherapy, 51% (88/172) for PSA persistence and 36% (62/172) for PSA recurrence after radical prostatectomy. An experienced radiation oncologist, blinded to the CT and PET/CT imaging results, decided on the radiation treatment management of all patients based on the clinical and pathological variables. The potential increase in diagnostic accuracy, and the subsequent change of radiotherapeutic approach was documented separately for PET/CT versus CT. Results: Overall detection rate was 70% (120/172) in ₆₈Ga-PSMA PET/CT. Patients with pre-PSMA PET/CT PSA-level >0.5 ng/ml (98/111; 88%) had significantly more often PET-positive results. Overall, PSMA PET/CT revealed a total of 171 lesions, PET alone 156 and CT alone 85. For all patients a continuous diagnostic increase in positive findings was observed for primary tumor/local recurrence (CT: 18% vs. PET/CT: 37%), pelvic lymph node (CT: 21% vs. PET/CT: 44%) and distant metastases (CT: 7% vs. PET/CT: 19%) when comparing CT vs. PET/CT. Compared to CT, the combination of PET/CT information resulted in a change of treatment in 107/172 (62%) patients, i.e. 8/22 (36%) patients prior to any treatment, 31/62 (50%) with PSA recurrence and 68/88 (77%) with PSA persistence. Comparing the different radiotherapy indications with each other, there was a higher change of management in postoperative patients vs. patients prior to any treatment. Conclusion: Compared to conventional CT, PSMA PET/CT had a remarkable impact on radiotherapeutic approach especially in postoperative patients. Thus, considering the growing amount of data on PSMA PET/CT’s impact in postoperative patients, PSMA PET/CT has recently been endorsed as an imaging modality in patients with PSA persistence/recurrence in a few cancer guidelines, for instance the German S3 guideline and the European association of urology guideline.

Purpose: Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [¹⁸F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard ⁶⁸Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. Methods: Eight NET patients received a [¹⁸F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying ¹⁸F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. Results: After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images. Conclusion: [¹⁸F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to ⁶⁸Ga-labelled alternatives. For clinical use of [¹⁸F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection.