Abstract
WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice
Medical physics (Lancaster), Vol.43(6), pp.3825-3826
06/2016
DOI: 10.1118/1.4957910
Abstract
Purpose:
The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver 225Ac: MC1RL-DOTA-225Ac.
Methods:
17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-225Ac radiopharmaceutical with an average initial administered activity of 2.5 µCi. After the injection, three groups of animals (6, 6, and 5 per group) were euthanized at 24, 48, and 96 hour time points. A total of 11 organs of interest were harvested at each time point including kidneys and liver. Since the emitted alpha particles from 225Ac and its daughter products are not easy to detect directly, the isomeric gamma spectra were measured instead in the tissue samples using a modified Atomlab™ Gamma Counter (Biodex Medical Systems, Inc) and converted using factors for gamma ray abundance per alpha decay. Dosimetry was performed using measured radioactivity distribution in organs and the generalized internal dosimetry schema of MIRD pamphlet #21.
Results:
Our calculations have shown that the maximum absorbed dose was delivered to the liver with a total of 47 cGy per 96 hour period. The average dose per kidney was calculated to be 21 cGy. Heart, brain, lung, spleen, skin doses ranged from 0.01 to 1 cGy over the same time period. All animals gained weight over the 110 day decay period and no organ damage was observed by pathology.
Conclusion:
Based on our results, the risk of using the MC1RL-DOTA-225Ac compound is relatively small in terms of deterministic radiation effects.
Funding Support: NIH/NCI P50CA168536-03 Skin SPORE; NIH/NCI Phase I SBIR Contract #HHSN261201500067C; Imaging and Technology Center of Excellence at Moffitt.
Disclosures and Conflict of Interest: Collaboration with Modulation Therapeutics, Inc.(MTI) and has been partially funded by sub-contracts from MTI via collaboration on a NIH/NCI phase I SBIR contract.
Details
- Title: Subtitle
- WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice
- Creators
- Christopher J. Tichacek - University of South FloridaNarges K. Tafreshi - Moffitt Cancer CenterMikalai M. Budzevich - Radiation Oncology, andEpifanio Ruiz - Radiation Oncology, andThaddeus J. Wadas - Modulation TherapeuticsMark L. McLaughlin - Department of Physics, Medical PhysicsEduardo G. Moros - University of South FloridaDavid L. Morse - 7Wake Forest School of Medicine, Departments of Radiology and Cancer Biology, Winston-Salem, NC
- Resource Type
- Abstract
- Publication Details
- Medical physics (Lancaster), Vol.43(6), pp.3825-3826
- DOI
- 10.1118/1.4957910
- ISSN
- 0094-2405
- eISSN
- 2473-4209
- Number of pages
- 2
- Date published
- 06/2016
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984315656002771
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