New PSMA Radiohybrid Combines PET Imaging With Alpha Therapy

A new preclinical study published in the Journal of Nuclear Medicine has investigated rhPSMA-10.1, a radiohybrid compound designed to combine PET imaging with targeted alpha therapy for prostate cancer.

The approach uses two closely related versions of the same PSMA-targeting molecule: ¹⁸F/La-rhPSMA-10.1 for PET imaging and ²²⁵Ac-rhPSMA-10.1 for treatment. Their similar chemical properties could allow researchers to predict how the therapeutic compound distributes throughout the body using its diagnostic counterpart.

The researchers evaluated the compounds in laboratory experiments and mice bearing human prostate cancer tumours, comparing the therapeutic version with the established experimental radioligand ²²⁵Ac-PSMA-I&T.

Tumour accumulation of ²²⁵Ac-rhPSMA-10.1 was approximately 2.2 times higher after one hour and 3.5 times higher after 24 hours compared with ²²⁵Ac-PSMA-I&T.

Both alpha-emitting treatments significantly suppressed tumr growth, with median survival exceeding 50 days, compared with 12 days in untreated controls. However, despite its higher tumour accumulation, rhPSMA-10.1 did not demonstrate superior antitumor efficacy over PSMA-I&T in this setting.

An important finding was the similar biodistribution of the diagnostic and therapeutic versions of rhPSMA-10.1. This suggests that PET imaging with the fluorine-18-labelled compound could help estimate the distribution of the actinium-225 treatment, potentially supporting more personalised radiation dosimetry.

The study builds on earlier preclinical investigations of rhPSMA-10.1 and provides additional evidence supporting its use as a paired diagnostic and therapeutic platform.

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