European Nuclear Medicine Guide
Unlike beta-emitters (177Lu, 90Y), alpha-emitters such as Actinium-225 and Lead-212 are characterized by higher energy (4–9MeV) and shorter tissue range (<0.1mm), mainly causing? DNA double-strand breaks, despite potentially increased toxicity [40].
212Pb has a 10.6-hour half-life and decays via a 6.1MeV alpha particle, while 225Ac has a 10-day half-life and decays via alpha particles with energies ranging from 5.9–8.5MeV [41,42].
Administered activities for alpha-emitters are up to 1000 times lower than those for beta-emitters, mostly resulting in significantly fewer detected photons. They are therefore not universally? suitable for high-quality image-based assessments and dosimetry, though dedicated scanners are being explored to overcome these sensitivity limitations.
In a retrospective study, [225Ac]Ac-DOTA-TATE (1–3 cycles, mean activity of 8.2 ± 0.6MBq) was administered in 11 G1/2 metastatic NET of different origin (bronchial, GEP, paraganglioma, and unknown primary site) mostly refractory to [177Lu]Lu-DOTA-TATE. Without any relevant toxicity, this alpha-therapy approach achieved a disease control rate in 8/11 patients with a median PFS of 12 months [43].
In a phase 1 activity-escalation study, 20 patients with unresectable or metastatic progressive NET of different origin and with positive somatostatin analogue scan received intravenous [212Pb]Pb-DOTAM(bifunctional chelator)-TATE. The authors observed an objective radiological response in 80% of the first 10 patients treated with the phase 2 recommended activity (4 cycles of 2.5MBq/Kg/cycle bimonthly), while 90% of the subjects demonstrated absence of disease progression at a median follow‐up time of 17.4 months. The alpha therapy was also well tolerated without serious AE, therapy delay or activity reduction [46].
Despite the limited data in the literature and the lack of official approval, alpha-emitter therapy is promising in NET, showing potential in overcoming radioresistance to beta-emitter SSTR therapy [44].