Radiolabelled RGD, an important theranostic ligand for targeting angiogenesis: bench to bedside

Angiogenesis, an essential phenomenon for tumor growth, invasion and metastasis is known to be associated with integrin αvβ3. Over-expression of this integrin have been observed on endothelial cells of neovasculature and in various malignancies. The present study aims to explore the potential of Ga-68 and Lu-177 labelled RGD tripeptide in breast, lung and TENIS patients. Reaction parameters were optimised in-house for radiolabeling of RGD with Ga-68 and Lu-177. Post quality control tests, biodistribution studies were performed in normal sprague dwaley rats. A total of 100 patients (n=80 and 5 for Breast and lung cancer respectively, and n=15 TENIS) have undergone Ga-68 RGD PET/CT scan. Two patents with TENIS have undergone Lu-177 RGD therapy. Radiolabeling yield of >95% and RCP of >99% was achieved under optimised conditions. The final preparation was observed to be sterile and the endotoxin content was found to less than 4 EU/ml and 15 EU/ml in Ga-68-RGD and Lu-177 RGD preparations respectively. Animal study revealed maximum counts in liver and spleen with excretion through kidneys at 45 min. Physiological uptake was observed in bilateral brain ventricles, liver, spleen with variable uptake in intestine at 45 min. Excretion was observed mainly via kidneys. Variable uptake (SUV_max 1.02-20.8) was observed in primary lesion. Good uptake of Lu-177 RGD was observed in primary and metastatic lesions. The tracer was well tolerated by the patients. The study suggested the radiolabelled RGD peptide has immense potential for becoming a theranostic agent for tumors expressing integrin αvβ3. (author)