Phase I Trial of [99mTc]Tc-maSSS-PEG2-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors

Abstract

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 [99mTc]Tc-maSSS-PEG2-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 [99mTc]Tc-maSSS-PEG2-RM26 (600–700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [99mTc]Tc-maSSS-PEG2-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 [99mTc]Tc-maSSS-PEG2-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 [99mTc]Tc-maSSS-PEG2-RM26 was safe and well tolerated. [99mTc]Tc-maSSS-PEG2-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies.

177Lu-labeled PSMA targeting therapeutic with optimized linker for treatment of disseminated prostate cancer; evaluation of biodistribution and dosimetry

“…The effective dose was calculated to be 0.00423 Sv/GBq, Obviously, upscaling from mice to humans is associated with multiple uncertainties ( 32 ). On the other hand, our upscaling of dosimetry of a bombesin-based imaging probe [ 99m Tc]Tc-maSSS-PEG2-RM26 (effective dose 0.00349 mSv/MBq) ( 33 ) showed to be in a reasonably good agreement with clinical data (0.0044 ± 0.0006 mSv/MBq) ( 34 ). As a first approximation, we compared the upscaling to humans of absorbed doses in different organs calculated for [ 177 Lu]Lu-BQ7876 in this study and for [ 177 Lu]Lu-PSMA-617 ( 35 ).…”

The GRPR Antagonist [99mTc]Tc-maSSS-PEG2-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity

“…Furthermore, it also showed a biodistribution profile suitable for GRPR-positive prostate cancer imaging and acceptable dosimetry estimations when tested on animal models [20]. Recently, [ 99m Tc]Tc-maSSS-PEG2 -RM26 was studied in a phase I clinical study, and it was demonstrated that single injections of this agent were well tolerated and were associated with low absorbed doses in healthy organs and tissues [27]. The agent was tested for SPECT imaging of prostate and breast cancer lesions, and a number of primary tumors of both origins, as well as breast cancer lymph node metastases, which were visualized shortly after administration (Figure 5).…”

Influence of Molecular Design on the Tumor Targeting and Biodistribution of PSMA-Binding Tracers Labeled with Technetium-99m

“…Moreover, since the position of the kidneys is well defined, the use of SPECT/CT makes it possible to distinguish the high radioactivity accumulation in the kidneys from other organs and tissues. In contrast, radioactivity in the gastrointestinal tract in the case of [ 99m Tc]Tc-BQ0411 and [ 99m Tc]Tc-BQ0412 is more problematic [37]. This can lead to false-positive findings because of the occasional formation of volumes with a high activity concentration in the content of the gastrointestinal tract.…”