Cheveau Maxime, Moreau Mathieu, Grohmann Anna, Robert Sarah, Cochet Alexandre, Collin Bertrand, Boschetti Fréderic, Poty Sophie, Denat Franck
Université Bourgogne Europe, CNRS, Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302, Dijon, France.
CheMatech, Dijon, France; and.
J Nucl Med. 2025 Sep 2;66(9):1396-1399. doi: 10.2967/jnumed.125.270234.
We report the synthesis and evaluation of the first 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane-3,6,10,13-tetraacetic acid (PYTA) bifunctional chelators (BFCs) for Ac coordination. Three PYTA BFCs (PYTA-triacetate, PYTA-glutaric acid, and PYTA-pyridyl-ether) were synthesized. A comparative radiolabeling study with MACROPA, DOTA, and crown derivatives was performed. Conjugation to prostate-specific membrane antigen ligands and antibodies exemplified the applicability of these BFCs. Biodistribution and long-term stability of radiocomplexes were investigated in vivo. PYTA derivatives demonstrated excellent radiochemical properties with quantitative radiolabeling under mild conditions (37 °C; low concentration) and exhibited prolonged in vitro stability. In vivo evaluation of radioimmunoconjugates confirmed the prolonged stability of PYTA conjugates, yielding results comparable to those seen with MACROPA, and revealed the instability of crown derivatives. PYTA emerges as a promising chelator for Ac, comparable to MACROPA, with the advantages of modular BFC synthesis.
我们报道了首例用于锕（Ac）配位的3,6,10,13-四氮杂-1,8(2,6)-二吡啶环十四烷-3,6,10,13-四乙酸（PYTA）双功能螯合剂（BFC）的合成与评估。合成了三种PYTA BFC（PYTA-三乙酸、PYTA-戊二酸和PYTA-吡啶基醚）。进行了与大环多胺（MACROPA）、二氧杂环辛烷（DOTA）和冠醚衍生物的比较放射性标记研究。与前列腺特异性膜抗原配体和抗体的偶联证明了这些BFC的适用性。在体内研究了放射性配合物的生物分布和长期稳定性。PYTA衍生物在温和条件下（37 °C；低浓度）进行定量放射性标记时表现出优异的放射化学性质，并在体外表现出延长的稳定性。放射性免疫偶联物的体内评估证实了PYTA偶联物的延长稳定性，产生的结果与MACROPA相当，并揭示了冠醚衍生物的不稳定性。PYTA作为一种用于锕的有前景的螯合剂出现，与MACROPA相当，具有模块化BFC合成的优点。
