Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy (RPT) with the alpha-emitter actinium-225 (225Ac) has shown promising activity in metastatic castration-resistant prostate cancer (mCRPC), but its use is limited by toxicity. A tandem approach combining [225Ac]Ac-PSMA-617 and [177Lu] Lu-PSMA-617 (actinium-lutetium) has been developed to mitigate adverse effects and optimize efficacy. Given the scarcity of 225Ac and the emergence of resistance, early identification of non-responders is crucial. Circulating tumor DNA (ctDNA), especially tumor fraction (TFx) estimated from ultra-low-pass whole genome sequencing (ULP-WGS) using ichorCNA, may provide a non-invasive biomarker for monitoring treatment response. Blood samples were collected from mCRPC patients treated with actinium-lutetium bimonthly. Cell-free DNA (cfDNA) was extracted and analyzed by ULP-WGS (≤ 7 × coverage). TFx was derived using ichorCNA and compared longitudinally with prostatespecific antigen (PSA) and imaging data.
AMGHAR Mariam;
RAUSCH Tobias;
OZGUR Hilal;
ROSCHER Mareike;
BAUDER-WÜST Ulrike;
BRUCHERTSEIFER Frank;
MORGENSTERN Alfred;
BENES Vladimir;
KRATOCHWIL Clemens;
BENESOVA-SCHÄFER Martina;
2026-06-23
SPRINGER
JRC141756
2191-219X (online),
https://link.springer.com/article/10.1186/s13550-026-01388-x,
https://publications.jrc.ec.europa.eu/repository/handle/JRC141756,
10.1186/s13550-026-01388-x (online),
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