^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

Abstract

99m Tc-3PRGD2 is a new SPECT tracer targeting integrin a V b 3 receptor for detecting tumors, imaging angiogenesis, and evaluating tumor response to therapy. A multicenter study was designed to investigate the efficacy of 99m Tc-3PRGD2 for the evaluation of patients with lung cancer. Methods: Seventy patients (51 men, 19 women; mean age 6 SD, 63 6 9 y) with a suspected lung lesion and for whom definite pathologic diagnosis was finally obtained (malignant, n 5 58; benign, n 5 12) were recruited from 6 centers. Whole-body planar scanning and chest SPECT were performed at 1 and 4 h, respectively, after intravenous injection of 11.1 MBq/kg (0.3 mCi/kg) of 99m Tc-3PRGD2. The images were read in consensus by 6 experienced nuclear medicine physicians masked to the source, history, and pathologic diagnosis. The tumor-to-background (T/B) ratios were calculated for semiquantitative analysis. A Student t test was used for statistical analysis, and a P value less than 0.05 was considered significant. Results: With low 99m Tc-3PRGD2 background in the lungs and mediastinum, most lung malignancies were prominent on the 1-h images (T/B ratio, 1.65 6 0.47 for the planar imaging and 2.78 6 1.52 for SPECT). The T/B ratios were significantly lower in the benign lesions (P , 0.05). The sensitivity was 88% for semiquantitative analysis and could reach 93%-97% in visual analysis when considering the volume effect, necrosis, and metastasis. However, the specificity was only 58%-67%. Most lymph node and bone metastases could also be detected. Conclusion: 99m Tc-3PRGD2 imaging at 1 h is sensitive for the detection of lung cancer, meriting further investigation of 99m Tc-3PRGD2 as a novel clinical tracer for integrin receptor imaging. Si nce integrins were revealed as an important family of transmembrane receptors about 30 y ago, they have been widely studied and are found to play essential roles in angiogenesis and tumor metastasis because they are mainly involved in the cell-cell and cell-matrix interactions (1). Integrin a V b 3 is an important member of this receptor family and expressed preferentially on various types of tumor cells and the activated endothelial cells of tumor angiogenesis but not at all or very little on the quiescent vessel cells and other normal cells (2,3). Therefore, the integrin a V b 3 receptor is becoming a valuable target for diagnosis and treatment of malignant tumors (4,5).The tripeptide sequence of arginine-glycine-aspartic acid (RGD) can specifically bind to the integrin a V b 3 receptor (6,7). Accordingly, a variety of radiolabeled RGD-based peptides have been developed for noninvasive imaging of integrin a v b 3 expression via PET or . Among all the RGD radiotracers studied, 2 PET agents, 18 F-galacto-RGD and 18 F-AH111585, have been well investigated in clinical trials. The results demonstrated that both radiotracers allowed the specific imaging of various types of tumors, and the tumor uptake correlated well with the expression of integrin a v b 3 in both animal models and patients (9-14). The 99m Tc...

Integrin αvβ3 Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using 99mTc-3PRGD2

“…99m Tc-3PRGD2 has recently been translated into clinical trials following its preliminary applications and several other RGD-based tracers' applications in preclinical experiments and clinical trial (10)(11)(12)15). A multicenter study of 99m Tc-3PRGD2 for integrin receptor imaging of lung cancer was organized by our department last year, and results indicated that 99m Tc-3PRGD2 imaging at 1 h was sensitive enough for the detection of lung cancer, with a sensitivity of 88% for semiquantitative analysis that could reach 93%-97% in visual analysis when considering the volume effect, necrosis, and metastasis (23). The present study is the first application of RGD imaging in DTC patients with RAIR lesions.…”

Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrinαvβ3–Targeted Radiotracer99mTc-3P-RGD2

“…Tc-3P-RGD 2 SPECT/computed tomography (CT) was also used for quantification of tumor radioactivity accumulation and delineation of tumor necrotic regions (Zhou et al, 2012b;Shao et al, 2013). It is currently under clinical investigation as a new SPECT radiotracer for imaging carcinomas of breast and lung in cancer patients Zhu et al, 2012).…”

Triple-phase 99mTc-3P-RGD2 imaging of peripheral primitive neuroectodermal tumor in the hip muscle group with bone metastasis

“…Furthermore, as pPNET is mainly diagnosed via pathological examination of biopsy samples or surgical specimens, more extensive investigations, such as nuclear medicine imaging, including whole-body technetium 99m bone scan or positron emission tomography imaging, are indicated (13). Tc-3P-RGD 2 , an integrin α v β 3 -targeted radiotracer, has completed a phase III clinical study for solid tumor imaging in China; it offers a major advantage for the differential diagnosis of solid tumors and metastasis, as well as for patient selection and evaluation for anti-angiogenic therapy (14)(15)(16)(17)(18). The mechanism underlying this imaging technique is the high expression of integrin α v β 3 on the endothelial cells of neovessels, tumor cells, and osteoclasts.…”