PT  - JOURNAL ARTICLE
AU  - Yang, Hua
AU  - Gao, Feng
AU  - Yuan, Zheliang
AU  - Rodriguez-Rodriguez, Cristina
AU  - Merkens, Helen
AU  - Robertson, Andrew
AU  - Radchenko, Valery
AU  - Causey, Patrick
AU  - Benard, Francois
AU  - Schaffer, Paul
TI  - A novel actinium bifunctional chelator Crown and biodistribution of Ac-225-Crown-TATE
DP  - 2020 May 01
TA  - Journal of Nuclear Medicine
PG  - 1235--1235
VI  - 61
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/61/supplement_1/1235.short
4100  - http://jnm.snmjournals.org/content/61/supplement_1/1235.full
SO  - J Nucl Med2020 May 01; 61
AB  - 1235Objectives: Actinium-225 is a promising isotope for targeted alpha therapy (TAT) because of its favorable half-life (9.9 days) and high cytotoxicity with the four alpha particle emissions. Currently, chelation strategies for actinium are limited, hindering its clinical application. The goal is to develop a new chelator for actinium that can coordinate under mild conditions and produce a stable complex in vivo. Methods: A new ligand named Crown was designed and synthesized. Crown is a macrocycle capable of accommodating large metal ions while retaining the structural simplicity and hydrophilicity. The labeling conditions at various concentrations, buffers and pH were tested. The chemical stability of Ac-225-Crown was assessed. The ligand was attached to octreotate (TATE) and the peptide conjugate was labeled with Ac-225. The serum stability and biodistribution of Ac-225-Crown-TATE in AR42J tumor-bearing-mice was studied. Results: Crown can form a stable complex with Ac-225 at room temperature and neutral pH quantitatively. Ac-225-Crown-TATE was stable in mice and human serum. Biodistribution in AR42J tumor bearing mice at 1h and 4h showed low liver accumulation (2.41±1.15 %ID/g at 1h and 2.44±1.15 %ID/g at 4h) indicating in vivo stability. The activity was primarily accumulated in kidneys, bladder and tumor (8.10±2.36 %ID/g at 1h and 6.55±0.88 %ID/g at 4h). Conclusions: Crown is a suitable ligand for actinium, and Ac-225-Crown-TATE is a promising candidate for further therapeutic studies.