Analysis of 100 studies with PSMA Lu177 and Ac225 suggest reductions in PSA, enhanced survival and low incidence of severe toxicity in MCRP

[Graham49]

An encouraging meta-analysis for the treatment of MCRP.

Dai YH, Chen PH, Lee DJ, Andrade G, Vallis KA. Prostate-specific membrane antigen radioligand therapy utilising lutetium-177 and actinium-225 in metastatic prostate cancer.

doi.org/10.1016/j.eururo.20...

Eur Urol. 2024 Sep 25:S0302-2838(24)02608-3. doi:10.1016/j.eururo.2024 .09.020

“A detailed literature search across PubMed/Medline, EMBASE, Web of Science, Scopus, and Cochrane Library was conducted, culminating in the inclusion of 100 studies involving 8711 patients. Data on prostate-specific antigen (PSA) responses, toxicity profiles, and QoL and survival outcomes were analysed. Proportional meta-analyses and meta-regression analyses were performed.”

“Key findings and limitations

The estimated proportion of patients with PSA decline ≥50% was 0.49 for [177Lu]Lu-PSMA and 0.60 for [225Ac]Ac-PSMA in mPCa, particularly metastatic castration-resistant prostate cancer. A meta-regression analysis indicated an association between the cumulative amount of administered activity and the proportion of PSA ≥50% decline. Positive PSA responses were observed alongside improved overall survival across both therapies. Our analyses also identified the key factors associated with PSA responses and survival outcomes, including baseline haemoglobin level, and the presence of visceral metastases. Although anaemia was commonly observed, with [177Lu]Lu-PSMA, severe toxicities were infrequent. Improved QoL was observed following [177Lu]Lu-PSMA therapy, whereas it remained stable following the second cycle of [225Ac]Ac-PSMA treatment. Heterogeneity across studies for PSA responses and toxicity profiles is a limitation.”

[SViking]

has anyone determined the long term side effects of actinium?

[Graham49 in reply to SViking]

I could not find any studies.

Lu177 emits beta particles and decays to Hf177 which is stable.

Ac225 emits alpha particles which don't travel as far, so might do less collateral damage. However there are another 7 decays to other elements (5 alpha emissions and 2 beta emissions) before stable thallium is reached.

So its not obvious to me whether Ac225 long term will be worse or less toxic than Lu177.