In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T

• DOI: 10.1007/s00259-022-05821-w
• Publication Date: 2022-05-12T04:02:46Z
• Authors: Eline A. M. Ruigrok; Giulia Tamborino; Erik de Blois; Stefan J. Roobol; Nicole Verkaik; Marijke De Saint-...; Mark W. Konijnenberg; Wytske M. van Wee...; Marion de Jong; Julie Nonnekens
• Keywords: Radionuclide therapy; Lutetium; Clonogenic assay; DOTA

Targeting the prostate-specific membrane antigen (PSMA) using lutetium-177-labeled PSMA-specific tracers has become a very promising novel therapy option for prostate cancer (PCa). The efficacy of this might be further improved by replacing β-emitting lutetium-177 with α-emitting actinium-225. Actinium-225 is thought to have higher therapeutic due high linear energy transfer (LET) emitted α-particles, which can increase amount and complexity induced DNA double strand breaks (DSBs). Here we evaluated relative biological effectiveness [225Ac]Ac-PSMA-I&T [177Lu]Lu-PSMA-I&T assessing in vitro binding characteristics, dosimetry, efficacy.The PSMA-expressing PCa cell line PC3-PIP was used all assays. First, displacement assays were performed, revealed similar characteristics between [177Lu]Lu-PSMA-I&T. Next, assessment number 53BP1 foci, marker (DSBs), showed that cells treated had slower DSB repair kinetics compared Additionally, clonogenic survival specific targeting caused dose-dependent decrease survival. Lastly, after dosimetric assessment, (RBE) found 4.2 times [177Lu]Lu-PSMA-I&T.We labeling PSMA-I&T or actinium-225 resulted indicating distinct effects observed study are not difference uptake two tracers. correlates assumption irradiation causes more complex, difficult DSBs irradiation. Furthermore, RBE underlines potential treatment PCa.