An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the a αvβ3-selective angiogenesis imaging agent 99mTc-NC100692

Background: The alpha(v)beta(3) integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the alpha(v)beta(3) integrin with Tc-99m-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions. Purpose: To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the alpha(v)beta(3)-avid imaging agent Tc-99m-NC100692 in patients with breast or lung cancer, and to assess its safety profile. Material and Methods: Twenty-five patients-15 with lung cancer and 10 with breast cancer-were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10-15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq Tc-99m-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination. Results: In patients with breast cancer, Tc-99m-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters. Conclusion: Scintigraphy with Tc-99m-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of Tc-99m-NC100692 is safe and well tolerated.