Phase I Trial of [Tc-99m]Tc-maSSS-PEG(2)-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors

• Published in: Cancers 2023, Vol.15 (6)
• Main Authors: Chernov, Vladimir, Rybina, Anastasiya, Zelchan, Roman, Medvedeva, Anna, Bragina, Olga, Lushnikova, Nadejda, Doroshenko, Artem, Usynin, Evgeniy, Tashireva, Liubov, Vtorushin, Sergey, Abouzayed, Ayman, Rinne, Sara S., Sörensen, Jens, Tolmachev, Vladimir, Orlova, Anna
• Format: Article
• Language: English
• Subjects: 99mTc; antagonist; GRPR; phase I trial
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15061631

The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [Tc-99m]Tc-maSSS-PEG(2)-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 mu g of [Tc-99m]Tc-maSSS-PEG(2)-RM26 (600-700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 +/- 0.0007 for male patients and 0.008 +/- 0.003 mSv/MBq for female patients. The accumulation of [Tc-99m]Tc-maSSS-PEG(2)-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was safe and well tolerated. [Tc-99m]Tc-maSSS-PEG(2)-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies.