Differences in the Renal Accumulation of Radiogallium-Labeled (Glu) Peptides Containing Different Optical Isomers of Glutamic Acid.

Acidic amino acid peptides have a high affinity for bone. Previously, we demonstrated that radiogallium complex-conjugated oligo-acidic amino acids possess promising properties as bone-seeking radiopharmaceuticals. Here, to elucidate the effect of stereoisomers of Glu in Glu-containing peptides [(Glu)] on their accumulation in the kidney, the biodistributions of [Ga]Ga-,'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-,'-diacetic acid-conjugated (l-Glu) ([Ga]Ga-HBED-CC-(l-Glu)), [Ga]Ga-HBED-CC-(d-Glu), [Ga]Ga-HBED-CC-(dl-Glu), and [Ga]Ga-HBED-CC-(d-Glu-l-Glu) were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [Ga]Ga-HBED-CC-(d-Glu-l-Glu) exhibiting the lowest level of kidney accumulation among these compounds. Repeated d- and l-peptides may be a useful method for reducing renal accumulation in some cases.