With four alpha (4He2+) particles in its decay chain, actinium-225 (225Ac, t1/2 = 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 &lt;10 and &gt;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.

Evaluation of actinium-225 radiolabeled cyclized alpha-melanocyte stimulating hormone (CycMSH) peptide for targeted alpha therapy (TAT)

ACS Spring Meeting 2021

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