Toward realization of ‘mix-and-use’ approach in 68Ga radiopharmacy: preparation, evaluation and preliminary clinical utilization of 68Ga-labeled NODAGA-coupled RGD peptide derivative

Abstract

IntroductionThe present article demonstrates a ‘mix-and-use’ approach for radiolabeling RGD peptide derivative with 68Ga, which is easily adaptable in hospital radiopharmacy practice. The radiotracer thus formulated was successfully used for positron emission tomography (PET) imaging of breast cancer in human patients. MethodsThe conditions for radiolabeling NODAGA-coupled dimeric cyclic RGD peptide derivative [NODAGA-(RGD)2] with 68Ga were optimized using 68Ga obtained from a 68Ge/68Ga generator developed in-house with CeO2-PAN composite sorbent as well as from a commercial 68Ge/68Ga generator obtained from ITG, Germany. Preclinical studies were carried out in C57BL/6 mice bearing melanoma tumors. The radiotracer was prepared in a hospital radiopharmacy using 68Ga obtained from ITG generator and used for monitoring breast cancer patients by positron emission tomography (PET) imaging. Results68Ga-NODAGA-(RGD)2 could be prepared with high radiolabeling yield (>98%) and specific activity (~50GBq/μmol) within 10min at room temperature by mixing 68Ga with the solution of the peptide conjugate. In vivo biodistribution studies showed significant uptake (5.24±0.39% ID/g) in melanoma tumor at 30min post-injection, with high tumor-to-background contrast. The integrin αvβ3 specificity of the tracer was corroborated by blocking study. Preliminary clinical studies in locally advanced breast cancer (LABC) patients indicated specifically high tumor uptake (SUVmax 10–15) with good contrast. ConclusionsThis is one of the very few reports which presents preliminary clinical data on use of 68Ga-NODAGA-(RGD)2 and the developed ‘mix-and-use’ holds tremendous prospect in clinical PET imaging using 68Ga.