Development of ⁶⁸Ga-human serum albumin as a PET imaging agent for diagnosis of acute inflammation

Human serum albumin (HSA) has potential for diagnosis and therapy in clinical setting. The purpose of experiments was to develop and evaluate $^{68}Ga$-HSA as a PET agent for diagnosis of acute inflammation. NOTA-HSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to HSA in 0.1 M sodium carbonate buffer (pH 9.5) and then purified using a PD-10 size-exclusion column. NOTA-HSA was labeled with $^{68}Ga$ at room temperature for 10 min, and 8.4% sodium hydrogen carbonate buffer was added for neutralization. $^{68}Ga$-NOTA-HSA was purified using alumina N plus light cartridge and $0.22{\mu}m$ syringe filter. Labeling efficiency and radiochemical purity were determined by ITLC-SG with 0.1 M citric acid. Biodistribution study was performed in a male BALB/c mice model of Carrageenan-induced acute inflammation. Animal PET study was performed in acute inflammation mice model after tail vein injection of $^{68}Ga$-HSA. This radiotracer showed high labeling efficiency (>99%) around pH 7. Biodistribution study showed higher inflamed footpad uptake than control footpad uptake. Animal PET study revealed 2 times higher uptake on inflamed footpad compared to control footpad. In these experiments, we developed $^{68}Ga$-HSA for acute inflammation PET imaging and evaluated it in a mouse disease model. The results demonstrated that $^{68}Ga$-HSA has potential as a PET imaging agent for diagnosis of acute inflammation.