Actinium-225 in targeted alpha-particle therapeutic applications

Abstract

Alpha particle-emitting isotopes are being investigated in radioimmunotherapeutic applications because of their unparalleled cytotoxicity when targeted to cancer and their relative lack of toxicity towards untargeted normal tissue. Actinium- 225 has been developed into potent targeting drug constructs and is in clinical use against acute myelogenous leukemia. The key properties of the alpha particles generated by 225Ac are the following: i) limited range in tissue of a few cell diameters; ii) high linear energy transfer leading to dense radiation damage along each alpha track; iii) a 10 day halflife; and iv) four net alpha particles emitted per decay. Targeting 225Ac-drug constructs have potential in the treatment of cancer.

Figure 1

The ²²⁵Ac decay scheme.

Figure 2

Bioluminescence imaging (BLI) of two groups of scid mice that were xenografted with Daudi tumor cells transfected with the green fluorescent protein (GFP) and firefly luciferase (FFLuc) genes [45]. Images were taken on day 17 (a) after treatment with [²²⁵Ac]DOTA-B4 or (b) untreated growth controls. In the scid model, the GFP⁺/FFLuc⁺ Daudi cells developed into macroscopic, disseminated tumors in the bone marrow and spleen as well as in kidneys, liver, lungs, ovaries, and adipose tissue. BLI clearly showed the presence of lymphoma in the untreated mice while no disease was detected in the mice treated with the [²²⁵Ac]DOTA-B4. (n.b., the scale bar indicate the value x 1E6 photons/sec/cm²).