@article {doi:10.1021/acs.bioconjchem.2c00465,
	title = {H3TPAN-Triazole-Bn-NH2: Tripicolinate Clicked-Bifunctional Chelate for [225Ac]/[111In] Theranostics},
	journal = {Bioconjugate Chem.},
	volume = {33},
	number = {12},
	year = {2022},
	note = {PMID: 36378809},
	pages = {2381-2397},
	abstract = {<p>A new, high-denticity, bifunctional ligand-H3TPAN-triazole-Bn-NH2-has been synthesized and studied in complexation with [225Ac]Ac3+ and [111In]In3+ for radiopharmaceutical applications. The bifunctional chelator is readily synthesized, using a high-yielding four-step prep, which is highly adaptable and allows for straightforward incorporation of different covalent linkers using CuI-catalyzed alkyne\&ndash;azide cycloaddition (click) chemistry. Nuclear magnetic resonance (NMR) studies of H3TPAN-triazole-Bn-NH2 with La3+ and In3+ metal ions show the formation of a single, asymmetric complex with each ion in solution, corroborated by density functional theory (DFT) calculations. Radiolabeling studies with [225Ac]Ac3+ and [111In]In3+ showed highly effective complexation, achieving quantitative radiochemical conversions at low ligand concentrations (\&lt;10\&ndash;6 M) under mild conditions (RT, 10 min), which is further accompanied by high stability in human serum. The bioconjugate-H3TPAN-triazole-Bn-Aoc-Pip-Nle-CycMSHhex-was prepared for targeting of MC1R-positive tumors, and the corresponding 111In-radiolabeled tracer was studied in vivo. SPECT/CT and biodistribution studies in C57BL/6J mice bearing B16-F10 tumors were performed, with the radiotracer showing good in vivo stability; tumor uptake was achieved. This work highlights a new promising and versatile bifunctional chelator, easily prepared and encouraging for 225Ac/111In theranostics.</p>},
	doi = {10.1021/acs.bioconjchem.2c00465},
	url = {https://doi.org/10.1021/acs.bioconjchem.2c00465},
	author = {Wharton, Luke and Zhang, Chengcheng and Zeisler, Jutta and Rodr{\'\i}guez-Rodr{\'\i}guez, Cristina and Osooly, Maryam and Radchenko, Valery and Yang, Hua and Lin, Kuo-Shyan and B{\'e}nard, Francois and Schaffer, Paul and Orvig, Chris}
}
