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

Prostate and breast cancers are the most common malignancies. Accurate diagnosis and staging of diseases are important for the prognosis and determination of treatment tactics. The gastrin-releasing peptide receptor is overexpressed in over 80% of estrogen receptor-positive breast cancers and in up to 100% of primary prostate cancers, particularly in prostate cancers of lower grades and smaller sizes. Our group has developed an imaging agent [[sup.99m] Tc]Tc-maSSS-PEG[sub.2] -RM26 suitable for the detection of gastrin-releasing peptide receptors' expression using SPECT. We aimed to perform a first-in-human study to test the safety of [[sup.99m] Tc]Tc-maSSS-PEG[sub.2] -RM26 administration, to study its biological distribution in normal organs, and to evaluate the agent's targeting of receptors in tumors. This phase I study was performed in six prostate and seven breast cancer patients. Single injections of the new agent were well tolerated and a number of prostate and breast cancer primary tumors as well as metastases were visualized with SPECT/CT shortly after administration. 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 [[sup.99m] Tc]Tc-maSSS-PEG[sub.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 µg of [[sup.99m] Tc]Tc-maSSS-PEG[sub.2] -RM26 (600-700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [[sup.99m] Tc]Tc-maSSS-PEG[sub.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 [[sup.99m] Tc]Tc-maSSS-PEG[sub.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 [[sup.99m] Tc]Tc-maSSS-PEG[sub.2] -RM26 was safe and well tolerated. [[sup.99m] Tc]Tc-maSSS-PEG[s