Validation study of ¹³¹I-RRL: assessment of biodistribution, SPECT imaging and radiation dosimetry in mice.

Tumor angiogenesis is important in the growth and metastasis of malignant tumors. In our previous study, we demonstrated that an arginine-arginine-leucine (RRL) peptide is a tumor endothelial cell-specific binding sequence that may be used as a molecular probe for the imaging of malignant tumors in vivo. The aim of the present study was to further explore the characteristics of 131I‑RRL by biodistribution tests, and to estimate the radiation dosimetry of 131I‑RRL for humans using mice data. The RRL peptide was radiolabeled with 131I by a chloramine-T (CH-T) method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. 131I‑RRL was injected intravenously into B16 xenograft-bearing Kunming mice. Biodistribution analysis and in vivo imaging were performed periodically. The radiation dosimetry in humans was calculated according to the organ distribution and the standard medical internal radiation dose (MIRD) method in mice. All data were analyzed by statistical and MIRDOSE 3.1 software. The labeling efficiency of 131I‑RRL reached 70.0±2.91% (n=5), and the radiochemical purity exceeded 95% following purification. In mice bearing B16 xenografts, 131I‑RRL rapidly cleared from the blood and predominantly accumulated in the kidneys, the stomach and the tumor tissue. The specific uptake of 131I‑RRL in the tumor increased over time and was significantly higher than that of the other organs, 24-72 h following injection (P<0.05). The ratio of tumor-to-skeletal muscle (T/SM) tissue exceeded 4.75, and the ratio of the tumor-to-blood (T/B) tissue peaked at 3.36. In the single-photon emission computed tomography (SPECT) imaging of Kunming mice bearing B16 xenografts, the tumors were clearly identifiable at 6 h, and significant uptake was evident 24-72 h following administration of 131I‑RRL. The effective dose for the adult male dosimetric model was estimated to be 0.0293 mSv/MBq. Higher absorbed doses were estimated for the stomach (0.102 mGy/MBq), the small intestines (0.0699 mGy/MBq), the kidneys (0.0611 mGy/MBq) and the liver (0.055 mGy/MBq). These results highlight the potential of 131I‑RRL as a ligand for the SPECT imaging of tumors. Administration of 131I‑RRL led to a reasonable radiation dose burden and was safe for human use.