Imaging of Integrin α v β 3 Expression in Lung Cancers and Brain Tumors Using Single-Photon Emission Computed Tomography with a Novel Radiotracer 99m Tc-IDA-D-[c(RGDfK)] 2

Abstract

Integrin α_vβ₃ is a molecular marker for the estimation of tumor angiogenesis and is an imaging target for radiolabeled Arg-Gly-Asp (RGD) peptides. In this study, the authors investigated the clinical efficacy and safety of a novel radiolabeled RGD peptide, ^99mTc-IDA-D-[c(RGDfK)]₂, for the imaging of integrin α_vβ₃ expression, as a measure of tumor angiogenesis in lung cancers and brain tumors. Five patients with lung cancers and seven with brain tumors underwent ^99mTc-IDA-D-[c(RGDfK)]₂ single-photon emission computed tomography (SPECT) imaging. Tumors were also assessed using ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography. Uptake of the radiotracer was expressed as the tumor-to-normal uptake ratio (TNR). All the lung cancers and brain tumors were well visualized on ^99mTc-IDA-D-[c(RGDfK)]₂ SPECT. TNR for ^99mTc-IDA-D-[c(RGDfK)]₂ was significantly higher than that for ¹⁸F-FDG in brain tumors (6.4 ± 4.1 vs. 0.9 ± 0.4). Proliferation index of brain tumors showed a significant positive correlation with TNR for ^99mTc-IDA-D-[c(RGDfK)]₂ and ¹⁸F-FDG. No laboratory and clinical adverse events were reported after ^99mTc-IDA-D-[c(RGDfK)]₂ injection. Their results suggest that ^99mTc-IDA-D-[c(RGDfK)]₂ is an efficacious and safe radiotracer for imaging integrin α_vβ₃ expression with potential application to monitoring the clinical efficacy of antiangiogenic agents in malignant tumors. In addition, this is the first clinical application of radiolabeled RGD peptides for SPECT imaging of brain tumors.