Author: Vinay K Banka, Mikalai Budzevich, William R. Gibbons, Mark L. McLaughlin, Jacob Moriarty, Eduardo G. Moros, David L. Morse, Christopher J. Tichacek, Thad J. Wadas 👨🔬
Affiliation: Modulation Therapeutics Inc, Moffitt Cancer Center, University of Iowa 🌍
Purpose: A targeted alpha therapy drug, 225Ac-MTI-201, has been developed targeting the Melanocortin 1 Receptor for metastatic uveal melanoma and is currently in FIH clinical trials. Since alpha emissions can’t be tracked in the clinic and the Medical Internal Radiation Dose (MIRD) schema is not adequate for alpha emission, two companion radiotracers were developed, 67Ga-MTI-201 and 64Cu-MTI-201. The two tracers were then compared via dose ratios between the tumor and OARs, magnitude of dose delivered and biodistribution studies relative to 225Ac for optimal choice of imaging companion agent.
Methods: Both radiotracers were subjected to preclinical trials with cohorts of male and female SCID-beige mice bearing MEL270 tumors. The cohorts were injected with about 8.6 MBq of either 67Ga-MTI-201 or 64Cu-MTI-201. PET scans were acquired at 1,4 and 24 hours for 64Cu while SPECT scans were acquired at 24, 48 and 120 hours for 67Ga. At each time point, the animals were humanely euthanized then organs were harvested for ex-vivo measurements in a dose calibrator. Biodistribution graphs were generated from time integrated activity curves then dosimetry was performed using the MIRD methodology.
Results: The average dose delivered across all organs for 67Ga and 64Cu were 2.72 mGy/MBq and 7.46 mGy/MBq whereas the standard deviation of dose was 3.63 mGy/MBq and 11.6 mGy/MBq respectively. The tumor to liver, kidney, intestine and liver:kidney dose ratios for 225Ac, 64Cu and 67Ga, respectively, were: 0.0679, 0.165, 3.75, 2.42, 0.54, 1.09, 0.408, 2.01, 1.53, 2.35, 1.67 and 1.53.
Conclusion: 64Cu-MTI-201 has a higher magnitude of dose delivered and seems to have a more similar biodistribution as 225Ac-MTI-201 but 67Ga has a higher specific tumor uptake as compared to 64Cu, ~3x as much. 67Ga also has a similar liver:kidney and tumor:intestine ratio as 225Ac. Considering these measurements, 67Ga is the better radiotracer for 225Ac-MTI-201.