α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies-Part 1

Abstract

With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their widespread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters.

Keywords: clinical trials; radiochemistry; radiotherapy; α-emitters.

FIGURE 1.

Comparison of therapeutic particle energies, particle ranges, LET, and DNA damage potencies.

FIGURE 2.

Indirect mechanisms increasing α-particle lethal potency, including cross-fire effect (CF), radiation-induced bystander effect (RIBE), and abscopal effect (AbsE) (6).

FIGURE 3.

Schematic representation of in vivo pretargeting (42). mAb = monoclonal antibody.

FIGURE 4.

Redistribution of α-emitter daughters: approaches to controlling their fate. (A) γ-ray spectroscopy of BALB/C mouse kidneys 96 h after injection of ²²⁵Ac-HuM195. Peaks (440 keV) indicate presence of nonequilibrium ²¹³Bi in kidneys. (Reprinted with permission of (50).) (B) Internalization and retention of ²¹³Bi and ²²¹Fr daughters in vitro after binding of ²²⁵Ac-J591 in LNCaP cells. (Reprinted with permission of (12).) (C) High-resolution autoradiography evaluating spread of ²²⁴Ra progeny (²¹²Pb) after intratumoral implantation of ²²⁴Ra wires in HCT15 tumor model in nude mice. Hematoxylin and eosin staining shows correlation with necrotic domains. (Reprinted with permission of (52).) (D) Gold-coated lanthanide phosphate nanoparticle allowing retention of ²²⁵Ac and its daughters (54). (E) Heavy-metal chelation effect on ²¹³Bi renal uptake 24 h after injection of ²²⁵Ac radioimmunotherapy. (F) Furosemide and chlorothiazide effect on ²²¹Fr and ²¹²Bi renal uptake 24 h after injection of ²²⁵Ac radioimmunotherapy. %ID = percentage injected dose; DMPS = 2,3-dimercapto-1-propanesulfonic acid; DTPA = diethylenetriaminepentaacetic acid; i.p. = intraperitoneally.