Ga-FAPI-2/4/46 have already been proposed as promising PET-tracers. However, the short half-life of 68 Ga (T1/2 68 min) creates problems with manufacture and delivery. 18 F (T1/2 110 min) labeling would result in a more practical large scale production and a cold-kit formulation would improve the spontaneous availability. The NOTA-chelator ligand FAPI-74 can be labeled with both 18 F-AlF (Aluminum-Fluoride) and 68 Ga. Here we describe the in-vivo evaluation of 18 F-FAPI-74 and a proof-of-mechanism of 68 Ga-FAPI-74 labeled at ambient temperature. Methods: In ten patients with lung cancer PET-scans were acquired at 10 min, 1h and 3h after administration of 259±26 MBq 18 F-FAPI-74. Physiological biodistribution and tumor uptake were semi-quantitatively evaluated based on SUV at each time-point. Absorbed doses were evaluated using OLINDA/EXM 1.1 and QDOSE dosimetry software with the dose calculator IDAC-Dose 2.1. Identical methods were used to evaluate one exam after injection of 263 MBq 68 Ga-FAPI-74. Results: The highest contrast was achieved 1 h p.i. in primary tumors, lymph node and distant metastases with SUVmax >10, respectively. The effective dose per 100 MBq administered activity of 18 F-FAPI-74 was 1.4±0.2 mSv and for 68 Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic 18 F-FAPI-74 PET-scan is even lower than that of PET-scans with 18 F-FDG and other 18 F-tracers; 68 Ga-FAPI-74 is comparable to other 68 Ga-ligands. FAPI-PET/CT supported target volume definition for guiding radiotherapy. Conclusion: High contrast and low radiation burden of FAPI-74 PET/CT favors multiple clinical applications. Centralized large-scale production of 18 F-FAPI-74 or decentralized cold-kit labeling of 68 Ga-FAPI-74 allows flexible routine use.
Introduction PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. Methods Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers. Results [177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased. Conclusion Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.
Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68 Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumours ('MITIGATE') (grant agreement number 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Materials and methods:The main objectives were evaluation of safety, biodistribution, dosimetry and preliminary tumor targeting of 68 Ga-NeoBOMB1 in patients with advanced TKI-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. 68 Ga-NeoBOMB1 was prepared using a kit procedure with a licensed 68 Ge/ 68 Ga generator. 3 MBq/kg body-weight were injected intravenously and safety parameters were assessed. PET/CT included dynamic imaging at 5 min, 11 min and 19 min as well as static imaging at 1, 2 and 3-4 h p.i. for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetics. Tumor targeting was assessed on a per-lesion and perpatient basis.Results: 68 Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield >97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 weeks. Dosimetry calculations revealed a mean adsorbed effective dose of 0.029 ± 0.06 mSv/MBq with highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7 ± 5.4% of injected dose 4h p.i.). Plasma metabolite analyses revealed high stability, metabolites were only detected in the urine. In three patients a significant uptake with increasing maximum standard uptake values (SUVmax at 2h p.i.: 4.3 to 25.9) over time was found in tumor lesions. Conclusion:This Phase I/IIa study provides safety data for 68 Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging and absorbed dose estimates are comparable to other 68 Ga-labelled radiopharmaceuticals used in clinical routine.
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