An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the α_vβ₃-selective angiogenesis imaging agent ^99mTc-NC100692

Abstract

Background: The α_vβ₃ integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the α_vβ₃ integrin with ^99mTc-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 α_vβ₃-avid imaging agent ^99mTc-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 ^99mTc-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, ^99mTc-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 ^99mTc-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 ^99mTc-NC100692 is safe and well tolerated.

Key words::

• Angiogenesis
• breast cancer
• lung cancer
• metastases
• radionuclide imaging

Acknowledgments

We acknowledge all our study co-investigators: Roland Bares, Radiologische Klinik d. Universität Tubingen, Germany; Douglas Collins, Mayo Clinic Rochester, Saint Mary's Hospital, Minnesota, USA; Gary Cook, Royal Marsden Hospital, UK; Carolyn Featherstone, North Glasgow University Hospital, Scotland; Mark Harries, Guy's and St. Thomas’ Hospitals, London, UK; Mountz James, University of Pittsburgh, Pennsylvania, USA; Marianne Nicolson, Aberdeen Royal Infirmary, UK; Rodolfo Nunez, MD Anderson Cancer Center, Houston, Texas, USA; Richard Wahl, Johns Hopkins Oncology Centre, Baltimore, Maryland, USA.

The study was financed with a grant from GE Healthcare, which also supplied the radiopharmaceutical.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.