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Title: WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice

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 {sup 225}Ac: MC1RL-DOTA-{sup 225}Ac. Methods: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-{sup 225}Ac 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 {sup 225}Ac 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 organsmore » 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-{sup 225}Ac 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.« less

Authors:
; ; ;  [1];  [2];  [3];  [4];  [4]; ;
  1. Small Animal Imaging Core, Tampa, FL (United States)
  2. Wake Forest School of Medicine, Departments of Radiology and Cancer Biology, Winston-Salem, NC (United States)
  3. Department of Chemistry, Tampa, FL (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22679079
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ABSORBED RADIATION DOSES; ALPHA DOSIMETRY; ALPHA PARTICLES; ANIMAL TISSUES; BIOMEDICAL RADIOGRAPHY; GAMMA RADIATION; MELANOMAS; MICE; RADIATION EFFECTS; TISSUE DISTRIBUTION

Citation Formats

Tichacek, Christopher J., Tafreshi, Narges K., Budzevich, Mikalai M., Ruiz, Epifanio, Wadas, Thaddeus J., McLaughlin, Mark L., H. Lee Moffitt Cancer Center & Research Institute, Modulation Therapeutics, Inc., Tampa, FL, Moros, Eduardo G., and Morse, David L. WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice. United States: N. p., 2016. Web. doi:10.1118/1.4957910.
Tichacek, Christopher J., Tafreshi, Narges K., Budzevich, Mikalai M., Ruiz, Epifanio, Wadas, Thaddeus J., McLaughlin, Mark L., H. Lee Moffitt Cancer Center & Research Institute, Modulation Therapeutics, Inc., Tampa, FL, Moros, Eduardo G., & Morse, David L. WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice. United States. doi:10.1118/1.4957910.
Tichacek, Christopher J., Tafreshi, Narges K., Budzevich, Mikalai M., Ruiz, Epifanio, Wadas, Thaddeus J., McLaughlin, Mark L., H. Lee Moffitt Cancer Center & Research Institute, Modulation Therapeutics, Inc., Tampa, FL, Moros, Eduardo G., and Morse, David L. Wed . "WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice". United States. doi:10.1118/1.4957910.
@article{osti_22679079,
title = {WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice},
author = {Tichacek, Christopher J. and Tafreshi, Narges K. and Budzevich, Mikalai M. and Ruiz, Epifanio and Wadas, Thaddeus J. and McLaughlin, Mark L. and H. Lee Moffitt Cancer Center & Research Institute and Modulation Therapeutics, Inc., Tampa, FL and Moros, Eduardo G. and Morse, David L.},
abstractNote = {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 {sup 225}Ac: MC1RL-DOTA-{sup 225}Ac. Methods: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-{sup 225}Ac 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 {sup 225}Ac 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-{sup 225}Ac 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.},
doi = {10.1118/1.4957910},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}