PT - JOURNAL ARTICLE AU - Gruber, Leonhard AU - Jimenez-Franco, Luis David AU - Decristoforo, Clemens AU - Uprimny, Christian AU - Glatting, Gerhard AU - Hohenberger, Peter AU - Schoenberg, Stefan O. AU - Reindl, Wolfgang AU - Orlandi, Fransesca AU - Mariani, Maurizio AU - Jaschke, Werner AU - Virgolini, Irene Johanna TI - MITIGATE-NeoBOMB1, a Phase I/IIa Study to Evaluate Safety, Pharmacokinetics and Preliminary Imaging of <sup>68</sup>Ga-NeoBOMB1, a Gastrin-releasing Peptide Receptor Antagonist, in GIST Patients AID - 10.2967/jnumed.119.238808 DP - 2020 Apr 01 TA - Journal of Nuclear Medicine PG - jnumed.119.238808 4099 - http://jnm.snmjournals.org/content/early/2020/04/23/jnumed.119.238808.short 4100 - http://jnm.snmjournals.org/content/early/2020/04/23/jnumed.119.238808.full AB - Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68Ga-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 68Ga-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. 68Ga-NeoBOMB1 was prepared using a kit procedure with a licensed 68Ge/68Ga 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 per-patient basis. Results: 68Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield &gt;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 68Ga-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 68Ga-labelled radiopharmaceuticals used in clinical routine.