First-in-human radiation dosimetry of the GRPR antagonist [68Ga]Ga-NOTA-PEG2-RM26 in patients with prostate and breast cancer

Abstract Background Gastrin-releasing peptide receptor (GRPR) is overexpressed in several malignant tumours, while its physiological expression in major organs, except for pancreas, is low. GRPR is therefore an interesting target in nuclear medicine. The GRPR-binding ligand, [ 68 Ga]Ga-NOTA-PEG 2 -RM26 has previously been proven safe in humans. This study evaluates human dosimetry of the radioligand using 12 cancer patients (6 women with breast cancer and 6 men with prostate cancer) based on PET-CT imaging at six timepoints post injection. The voided urine was also collected to serve as an input to a urinary bladder model. Results The pancreas, liver, spleen, kidney parenchyma, gall bladder, urinary bladder contents and cortical bone were identified as source organs/regions. Results using OLINDA/EXM 2.3.0 dosimetry software showed that pancreas was the organ that received the highest absorbed dose, 110 ± 43 µGy/MBq, followed by the urinary bladder wall, 100 ± 36 µGy/MBq, and the kidneys, 31 ± 11 µGy/MBq. The osteogenic cells received 15 ± 7 µGy/MBq. The median (range) of the total excreted activity through urine was 56% (43–75%) of the injected activity in 4h. The effective dose (ICRP 103) from an injection of [ 68 Ga]Ga -NOTA-PEG 2 -RM26 was calculated to 11 µSv/MBq, using a 1h voiding interval in the urinary bladder model. Conclusion A standard person of 70kg receiving 140MBq of [ 68 Ga]Ga-NOTA-PEG 2 -RM26 will receive an effective dose of 1.5 mSv, which is lower or in accordance with other 68 Ga-labelled GRPR targeted radioligands. Trial registration Clinicaltrials.gov, NCT06147362, Registered 17 November 2023 – Retrospectively registered, https://www.clinicaltrials.gov/study/NCT06147362