Session: General Topics in Nuclear Chemistry and Technology:

With four alpha (⁴He²⁺) particles in its decay chain, actinium-225 (²²⁵Ac, t_1/2 = 9.9 d) is ideal for incorporation into radiopharmaceuticals for targeted alpha therapy (TAT) of cancer. Tumour targeting biomolecules allow for site-specific delivery of radioactive emissions to the disease cell. Lactam-bridged cyclized α-melanocyte stimulating hormone (CycMSH) peptide has high affinity for over expressed surface receptors on most malignant melanomas, making it a promising target for melanoma therapy. Herein, ²²⁵Ac-labeled CycMSH derivatives were evaluated as novel TATs for melanoma in a preclinical mouse model. DOTA- and macropa-CycMSH conjugates were radiolabelled with ²²⁵Ac with radiochemical yields (RCY) of <10 and >99 %, respectively. Low % RCY of the DOTA-conjugate precluded in vivo evaluation. The biodistribution of ²²⁵Ac-macropa-CycMSH (molar activity, S.A. = 1.38 kBq/pmol) in B16F10 tumour-bearing mice (n = 4) was evaluated for 2 different injected radioactivities (103.6 kBq and 51.8 kBq) 2 h post-injection and was found to be 2.50 and 0.67 % injected dose/gram in tumour. The moderate-to-low tumour uptake highlights the need for development of efficient and robust ²²⁵Ac chelators that produce high S.A. radiopharmaceuticals with favourable biodistribution.

<b>Figure 1</b>: The biodistribution 2 hours post injection of <sup>225</sup>Ac-Macropa-CycMSH in B16F10 tumour-bearing mice (n = 4) for dose 1 (diagonal lines) and dose two (checkered).

Figure 1: The biodistribution 2 hours post injection of ²²⁵Ac-Macropa-CycMSH in B16F10 tumour-bearing mice (n = 4) for dose 1 (diagonal lines) and dose two (checkered).

Caterina Ramogida

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