[225Ac]Ac-DOTA-Substance-P

[225Ac]Ac-DOTA-Substance-P is an investigational targeted alpha therapy (TAT) radiopharmaceutical developed for the treatment of malignant brain tumors, particularly recurrent glioblastoma multiforme (GBM). The compound consists of the high-energy alpha-emitting radionuclide actinium-225 ([225Ac]Ac) chelated by DOTA and conjugated to a metabolically stabilized analogue of the neuropeptide Substance P ([Thi8,Met(O2)11]-Substance P). Substance P serves as the targeting vector, binding with high affinity and specificity to the neurokinin-1 receptor (NK1R), which is highly overexpressed on glioblastoma cells and the tumor neovasculature. Upon binding and subsequent internalization, the decay of actinium-225 releases short-range, highly cytotoxic alpha particles that induce double-stranded DNA breaks, selectively destroying the cancer cells while minimizing radiation exposure to surrounding healthy brain tissue.

Other names

[225Ac]Ac-DOTA-[Thi8,Met(O2)11]-SP[225Ac]Ac-DOTA-[Thi8,Met(O2)11]-substance Pactinium-225 DOTA-SPactinium225 DOTA-SPactinium 225 DOTA-SPactinium-225 DOTA-substance Pactinium225 DOTA-substance Pactinium 225 DOTA-substance P