Tc-99m-RRL as a Novel Radiolabeled Tumor Angiogenesis Molecular Probe in Detection of Pulmonary Metastases

Objectives: Peptide RRL can specifically bind to tumor angiogenesis. A Tc-99m labeled RRL was developed as a promising probe for detection tumors. In the previous study, we demonstrated that Tc-99m radiolabeled arginine-arginine-leucine (RRL) could be used to non-invasively image malignant tumors. To improve the detection of pulmonary metastases, experimental blood-borne pulmonary metastasis mouse models were established using three intravenously administered cell lines. In a previous study we demonstrated that Tc-99m radiolabeled RRL could be used to non-invasively image malignant tumors. Methods. The RRL peptide was designed and radiosynthesized with Tc-99m by a one-step

Methods: The animal model was established. Tc-99m RRL was prepared and injected intravenously in mice with pulmonary metastases that arose from the intravenous injection of HepG2, B16, and Hela cells. All animal experiments were approved by the authority of Peking University Animal Studies Committee in accordance with the Guidelines for the Care and Use of Research Animals (Approval ID: J201312). The biodistribution and imaging of Tc-99m RRL were determined in different pulmonary metastases models and in normal mice. Results: Tc-99m RRL exhibited higher uptake values in the lungs of pulmonary metastatic mice compared with normal mice (P<0.01; 3.92 ± 0.48 %ID/g 2 h post-injection and 3.89 ± 0.36 %ID/g 4 h post-injection in metastatic hepatic carcinoma [HepG2]-bearing lungs; 5.49 ± 0.84 %ID/g 2 h post-injection and 5.11 ± 0.75 %ID/g 4 h post-injection in metastatic melanoma [B16]-bearing lungs; 3.72 ± 0.52 %ID/g 2 2 h post-injection and 3.51 ± 0.35 %ID/g 4 h post-injection in metastatic cervical carcinoma [Hela]-bearing lungs; 2.38 ± 0.20 %ID/g 2 h post-injection and 2.11 ± 0.24 %ID/g 4 h post-injection in normal lungs). The pulmonary metastatic lesions were clearly visualized with Tc-99m RRL. Conclusions: Peptide RRL highlights its potential as an effective imaging probe for detection of pulmonary metastases. Keywords: Technetium-99m; Peptide; Tumor angiogenesis; Lung metastasis; Non-invasive imaging