[^99mTc]Tc-DB15 in GRPR-Targeted Tumor Imaging with SPECT: From Preclinical Evaluation to the First Clinical Outcomes

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Chemistry

Background:

• Gastrin-releasing peptide receptor (GRPR)-antagonists are promising for diagnostic imaging and radionuclide therapy of prostate cancer (PC) and breast cancer (BC).
• Development of targeted radiotracers is crucial for improving diagnostic accuracy and therapeutic efficacy in oncology.

Purpose of the Study:

• To introduce and evaluate a novel GRPR-antagonist based radiotracer, [99mTc]Tc-DB15, for diagnostic imaging of GRPR-positive tumors using SPECT/CT.
• To assess the in vitro and in vivo performance of [99mTc]Tc-DB15 in preclinical cancer models and in patients with advanced breast cancer.

Main Methods:

• Synthesis and characterization of the GRPR-antagonist DB15 and its technetium-99m labeled form, [99mTc]Tc-DB15.
• In vitro studies using mammary (T-47D) and prostate cancer (PC-3) cell lines to determine GRPR-binding affinity and specificity.
• In vivo evaluation in PC-3 and T-47D xenograft-bearing mice, and SPECT/CT imaging in patients with advanced breast cancer.

Main Results:

• DB15 exhibited high GRPR affinity (IC50 = 0.37 ± 0.03 nM).
• [99mTc]Tc-DB15 demonstrated strong binding to GRPR-positive cancer cells and showed high, prolonged, GRPR-specific tumor uptake in mice with rapid clearance from background tissues.
• SPECT/CT imaging in patients with advanced breast cancer successfully identified bone and soft tissue metastases.

Conclusions:

• The novel radiotracer [99mTc]Tc-DB15 possesses excellent GRPR-targeting capabilities and favorable pharmacokinetic properties.
• Its ability to visualize GRPR-positive tumors in both preclinical models and human patients suggests significant potential for broader clinical application in diagnosing and potentially treating prostate and breast cancer.
• Ongoing clinical studies are exploring the full clinical utility of [99mTc]DB15.