Synthesis and in vivo evaluation of gallium‐68‐labeled glycine and hippurate conjugates for positron emission tomography renography

The objective of this study was to evaluate four new ⁶⁸Ga‐labeled 1,4,7,10‐cyclododeca‐1,4,7,10‐tetraacetic acid (DOTA)/1,4,7‐triazacyclononane‐1,4,7‐triacetic acid derived (NODAGA)‐glycine/hippurate conjugates and select a lead candidate for potential application in positron emission tomography (PET) renography. The non‐metallated conjugates were synthesized by a solid phase peptide synthesis method. The ⁶⁸Ga labeling was achieved by reacting an excess of the non‐metallated conjugate with ⁶⁸GaCl₄^? at pH ?4.5 and 10‐min incubation either at room temperature for NODAGA or 90 °C for DOTA. Radiochemical purity of all ⁶⁸Ga conjugates was found to be >98%. ⁶⁸Ga‐NODAGA‐glycine displayed the lowest serum protein binding (0.4%) in vitro among the four ⁶⁸Ga conjugates. Biodistribution of ⁶⁸Ga conjugates in healthy Sprague Dawley rats at 1‐h post‐injection revealed an efficient clearance from circulation primarily through the renal–urinary pathway with <0.2% of injected dose per gram remaining in the blood. The kidney/blood and kidney/muscle ratios of ⁶⁸Ga‐NODAGA‐glycine were significantly higher than other ⁶⁸Ga conjugates. On the basis of these results, ⁶⁸Ga‐NODAGA‐glycine was selected as the lead candidate. ⁶⁸Ga‐NODAGA‐glycine PET renograms obtained in healthy rats suggest ⁶⁸Ga‐NODAGA‐glycine as a PET alternate of ^99mTc‐Diethylenetriaminepentaacetic acid (DTPA).