Development of Targeted Alpha Particle Therapy for Solid Tumors

Narges K. Tafreshi; Michael L. Doligalski; Christopher J. Tichacek; Darpan N. Pandya; Mikalai M. Budzevich; Ghassan El-Haddad; Nikhil I. Khushalani; Eduardo G. Moros; Mark L. McLaughlin; Thaddeus J. Wadas; David L. Morse

doi:10.3390/molecules24234314

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Development of Targeted Alpha Particle Therapy for Solid Tumors

Journal article

Open access

Peer reviewed

Development of Targeted Alpha Particle Therapy for Solid Tumors

Narges K. Tafreshi, Michael L. Doligalski, Christopher J. Tichacek, Darpan N. Pandya, Mikalai M. Budzevich, Ghassan El-Haddad, Nikhil I. Khushalani, Eduardo G. Moros, Mark L. McLaughlin, Thaddeus J. Wadas, …

Molecules (Basel, Switzerland), Vol.24(23), p.4314

12/01/2019

DOI: 10.3390/molecules24234314

PMCID: PMC6930656

PMID: 31779154

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https://doi.org/10.3390/molecules24234314View

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Abstract

Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting alpha-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (alpha) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the alpha-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date.

Biochemistry & Molecular Biology

Chemistry

Chemistry, Multidisciplinary

Life Sciences & Biomedicine

Physical Sciences

Science & Technology

Details

Title: Subtitle: Development of Targeted Alpha Particle Therapy for Solid Tumors
Creators: Narges K. Tafreshi - Moffitt Cancer Center
Michael L. Doligalski - Moffitt Cancer Center
Christopher J. Tichacek - Moffitt Cancer Center
Darpan N. Pandya - Wake Forest University
Mikalai M. Budzevich - Moffitt Cancer Center
Ghassan El-Haddad - Moffitt Cancer Center
Nikhil I. Khushalani - Moffitt Cancer Center
Eduardo G. Moros - Moffitt Cancer Center
Mark L. McLaughlin - West Virginia University
Thaddeus J. Wadas - Wake Forest University
David L. Morse - Moffitt Cancer Center
Resource Type: Journal article
Publication Details: Molecules (Basel, Switzerland), Vol.24(23), p.4314
DOI: 10.3390/molecules24234314
PMID: 31779154
PMCID: PMC6930656
NLM abbreviation: Molecules
ISSN: 1420-3049
eISSN: 1420-3049
Publisher: Mdpi
Number of pages: 48
Grant note: Melanoma Research Alliance Team Science Award NIH/NCI SBIR Phase 1 NIH/NCI SBIR Phase 2 P50CA168536-03 / NIH/NCI-Moffitt Skin Cancer SPORE
Language: English
Date published: 12/01/2019
Academic Unit: Radiology; Radiation Oncology
Record Identifier: 9984312982602771

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