Synthesis and in vivo evaluation of gallium‐68‐labeled glycine and hippurate conjugates for positron emission tomography renography. (29th December 2014)

• Record Type: Journal Article
• Authors: Pathuri, Gopal; Hedrick, Andria F.; January, Spenser E.; Galbraith, Wendy K.; Awasthi, Vibhudutta; Arnold, Charles D.; Cowley, Benjamin D.; Gali, Hariprasad
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 58:Number 1(2015)
• Page Start: 14
• Page End: 19
• Publication Date: 2014-12-29
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3255
• Languages: English
• ISSNs: 0362-4803

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The objective of this study was to evaluate four new <sup>68</sup>Ga‐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 <sup>68</sup>Ga labeling was achieved by reacting an excess of the non‐metallated conjugate with <sup>68</sup>GaCl<sub>4</sub><sup>−</sup> at pH −4.5 and 10‐min incubation either at room temperature for NODAGA or 90 °C for DOTA. Radiochemical purity of all <sup>68</sup>Ga conjugates was found to be >98%. <sup>68</sup>Ga‐NODAGA‐glycine displayed the lowest serum protein binding (0.4%) <italic>in vitro</italic> among the four <sup>68</sup>Ga conjugates. Biodistribution of <sup>68</sup>Ga 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 <sup>68</sup>Ga‐NODAGA‐glycine were significantly higher than other <sup>68</sup>Ga conjugates. On the basis of these results, <sup>68</sup>Ga‐NODAGA‐glycine was selected as the lead candidate. <sup>68</sup>Ga‐NODAGA‐glycine PET renograms obtained in healthy rats suggest <sup>68</sup>Ga‐NODAGA‐glycine as a PET alternate of <sup>99m</sup>Tc‐Diethylenetriaminepentaacetic acid (DTPA).</p> </abstract>