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A new alpha-emitting radiopharmaceutical therapy (RPT) for advanced prostate cancer was well tolerated, with no dose-limiting toxicities observed, and showed encouraging signs of antitumor activity, according to a trial published in The Journal of Nuclear Medicine's Late-Breaking Fast Track.

Among patients treated with ²¹²Pb-ADVC001, 80% experienced a decline in prostate-specific antigen (PSA) levels of at least 50%, and the overall response rate was 100%. The findings support further clinical development of ²¹²Pb-ADVC001 to address the unmet needs in metastatic prostate cancer.

Prostate-specific membrane antigen (PSMA)–targeted RPT is an established treatment for metastatic androgen pathway modulation-resistant prostate cancer (mAPM-R, formerly metastatic castration-resistant prostate cancer). Although ¹⁷⁷Lu-PSMA-617, a beta-emitting RPT, has shown improved overall and radiographic progression-free survival in pivotal trials, approximately one-third of patients are resistant to ¹⁷⁷Lu-PSMA, and most responders progress during or soon after treatment.

"Current RPTs use fixed dosing regimens that do not account for variability in tumor response," said the study authors. "These limitations highlight the need for novel treatment strategies that may enhance patient outcomes using more potent payloads and optimization of dose and schedule."

Alpha-emitting RPTs have emerged as a new treatment approach: unlike beta emitters such as ¹⁷⁷Lu, which release lower-energy particles that travel up to a couple of millimeters, alpha emitters release high-energy particles that travel only a few cell widths, delivering concentrated radiation to cancer cells while sparing surrounding healthy tissue.

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