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.

Keywords: 99mTc; GRPR; antagonist; phase I trial.

Figure 1

Flow diagram according to Standards for Reporting of Diagnostic Accuracy Studies for PCa patients.

Figure 2

Flow diagram according to Standards for Reporting of Diagnostic Accuracy Studies for BCa patients.

Figure 3

Representative anterior and posterior images of patients with (a) PCa (P2) and (b) BCa (B6) 2, 4, 6, and 24 h pi of [^99mTc]Tc-maSSS-PEG₂-RM26.

Figure 4

Kinetics of whole body elimination (a) and blood (b) clearance of [^99mTc]Tc-maSSS-PEG₂-RM26.

Figure 5

CT (a) and fused SPECT/CT (b) images of PCa patient (P1, adenocarcinoma) 2 h after injection of [^99mTc]Tc-maSSS-PEG₂-RM26. A focus of increased [^99mTc]Tc-maSSS-PEG₂-RM26 uptake (SUVmax = 1.21) is visualized in the prostate (yellow arrow). The upper setting of the scale window (24% of the maximum number) was adjusted to visualize the lesion. Moderate (2+) GRPR expression in adenocarcinoma cells (c) was detected by IHC analysis in tumor material (black arrow). Magnification 40×.

Figure 6

CT (a,d) and fused SPECT/CT (b,e) images of BCa patient (B2, invasive carcinoma) 2 h after injection of [^99mTc]Tc-maSSS-PEG₂-RM26. A focus of increased [^99mTc]Tc-maSSS-PEG₂-RM26 uptake (SUVmax = 1.75) is visualized in the right breast ((b), yellow arrow). An enlarged (up to 1.3 cm) right axillary node with elevated [^99mTc]Tc-maSSS-PEG₂-RM26 uptake (SUVmax = 1.8) is visualized ((e), white arrow).The upper setting of the scale window (24% of the maximum number) was adjusted to visualize the lesion. Light (1+) GRPR expression and moderate (2+) expression (black arrow) in carcinoma cells were detected by IHC analysis in primary BCa tumor (c) and in LN (f). Magnification 40×.