Differences in the Renal Accumulation of Radiogallium-Labeled (Glu)14 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)₁₄] on their accumulation in the kidney, the biodistributions of [⁶⁷Ga]Ga-<i>N</i>,<i>N</i>'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-<i>N</i>,<i>N</i>'-diacetic acid-conjugated (l-Glu)₁₄ ([⁶⁷Ga]Ga-HBED-CC-(l-Glu)₁₄), [⁶⁷Ga]Ga-HBED-CC-(d-Glu)₁₄, [⁶⁷Ga]Ga-HBED-CC-(dl-Glu)₁₄, and [⁶⁷Ga]Ga-HBED-CC-(d-Glu-l-Glu)₇ were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [⁶⁷Ga]Ga-HBED-CC-(d-Glu-l-Glu)₇ 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.