Safety and Efficacy of 99mTc-hydrazinonicotinamide-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2) SPECT/CT for Integrin αVβ3 Imaging of Lung Cancer and Mapping Lymph Node Metastases: A Prospective Multicenter, Self-controlled, Phase 3 Trial

Accurate evaluation of lymph node metastasis plays a pivotal role in optimizing the surgical intervention and other precision treatments for lung cancer. CT-based nodal staging of lung cancer has limitation due to its low sensitivity, which relies on variations in tumor's size and structure. 18F-FDG PET/CT demonstrates low specificity owing to the nonspecific uptake in inflammatory lymph nodes, typically necessitating additional invasive mediastinal staging. Integrin αVβ3-targeted imaging could potentially bridge this existing technical gap. As a member of integrin family, integrin αVβ3 plays a crucial role in mediating tumor formation, invasion, metastasis, and angiogenesis. Therefore, integrin αVβ3 is an attractive target for tumor diagnosis and therapy. However, as of today, no drug has been approved for either diagnosis or therapy by targeting integrin αVβ3.

A diagnostic drug targeting integrin αvβ3, technetium-99m [99mTc] labeled hydrazinonicotinamide-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2), has been developed for imaging of lung cancer and other tumors via single photon emission computed tomography/ X-ray computed tomography (SPECT/CT). After intravenous injection into the body, 99mTc-3PRGD2 is expected to be specifically taken up by integrin αVβ3-positive tumors. The images obtained by SPECT/CT will be used for diagnosis and evaluation of the tumors, thereby guiding the individualized treatments including surgical intervention.

A prospective, multicenter, self-controlled phase 3 clinical trial is designed to evaluate the safety and efficacy of an integrin αVβ3-targeted imaging, 99mTc-3PRGD2 SPECT/CT, for diagnosis of lung cancer, with mapping the lymph node metastases as the primary objective. The secondary objectives include evaluation of 99mTc-3PRGD2 SPECT/CT in detection of lung cancer and the safety of 99mTc-3PRGD2 injection in human beings. The pathological results will be considered as the gold standard and the conventional metabolic imaging by 18F-FDG PET/CT will be used for a head-to-head comparison.

More than 400 patients with suspected lung cancer are designed to be recruited from 11 medical centers. Participants who meet the inclusion and exclusion criteria will be recruited to undergo SPECT/CT planar scan and chest tomography after intravenous injection of 99mTc-3PRGD2 at a dose of 0.3 mCi/kg. They will also undergo 18F-FDG PET/CT within a week. Among them, the patients who successfully complete safety tests are included into the safety analysis set.

At least 270 participants are expected to undergo lung lobectomy and lymph node station resection within 2 weeks after the 99mTc-3PRGD2 SPECT/CT. Their pathological results will be collected and used as the gold standard to evaluate the diagnostic efficacy of 99mTc-3PRGD2 SPECT/CT for diagnosis of lung tumors and lymph node metastases, with a head-to-head comparison with 18F-FDG PET/CT. Those patients who undergo lung surgery and lymph node resection within two weeks after the 99mTc-3PRGD2 SPECT/CT will be included into the efficacy analysis set to evaluate the efficacy of the imaging method in diagnosis of lung cancer and mapping the lymph node metastases.