Table 4.

225Ac-PSMA-617.

225Ac-PSMA-617	Information
	α-radiation emitters considered for clinical use: 213Bi, 212Pb, 227Th, and 225Ac. 225Ac-PSMA-617 studies stand out.
Pharmacokinetics
PSMA Antibody Connection	After binding with PSMA antibody, 225Ac emits 4 α particles and 2 β particles after fission.
Kidney Uptake	Early release of free 213Bi and tagged antibodies (225Ac) leads to excessive kidney uptake.
Tumor Uptake	90% maximal tumor uptake can last four days.
Half-Life	9.9 days, effective radioisotope with short radiation range (~0.1mm) and higher energy (~100keV).
Treatment Effects
PSA Decrease	Kratochwil et al.: 87% PSA decrease, 63% >50% PSA decrease, lasting 9 months.
Optimal Dosage	Dosimetry suggests 100kBq/kg/cycle with eight-week breaks between cycles.
PSA Response	PSA decrease lasts 4 months, improves during subsequent cycles (every 2 months).
Quality of Life	Sathekge et al.: Improved quality of life, decreased bone pain, minimal side effects.
PFS and OS	Median PFS 15 months, OS 18 months.
	87% PSA response, >70% >50% PSA decrease, median PFS 12 months, OS 17 months.
	13% complete remission, PSA decrease in 82%, 90% decrease in PSA in 82%, half had undetectable PSA for 12 months.
Combination Therapy	Better therapeutic effects with mixture of radionuclides including 225AcPSMA-617 and 177Lu-PSMA-617.
Side Effects
Kidney Toxicity	Yadav et al.: Kidney toxicity observed in 60% due to nuclides formed from 225Ac dissolution.
	Chronic kidney disease population showed toxicity.
Other Toxicity	Limited toxicity (levels 1 and 2) with xerostomia (85% cases), xerophthalmia, weight loss.
	Low toxicity reported.
Dynamic De-Escalation	Bruchertseifer et al.: Decreased toxicity with "dynamic de-escalation" of dosages.
	Sathekge et al.: Reduced salivary gland toxicity with dynamic deescalation.