Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan.
Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan.
Molecules. 2024 Aug 23;29(17):3993. doi: 10.3390/molecules29173993.
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.
酸性氨基酸肽对骨骼具有高亲和力。先前，我们证明了放射性镓络合的寡酸性氨基酸具有作为亲骨性放射性药物的有前途的特性。在这里，为了阐明含谷氨酸肽（Glu）中 Glu 的立体异构体对其在肾脏中积累的影响，比较了[Ga]Ga-，' -双-[2-羟基-5-（羧乙基）苄基]乙二胺-，' -二乙酸共轭（l-Glu）（[Ga]Ga-HBED-CC-（l-Glu））、[Ga]Ga-HBED-CC-（d-Glu）、[Ga]Ga-HBED-CC-（dl-Glu）和[Ga]Ga-HBED-CC-（d-Glu-l-Glu）的生物分布。尽管这些化合物在骨骼中的积累相当，但它们在肾脏中的积累和保留却明显不同，其中[Ga]Ga-HBED-CC-（d-Glu-l-Glu）在这些化合物中表现出最低的肾脏积累水平。重复的 d-和 l-肽可能是在某些情况下减少肾脏积累的有用方法。
