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Chelators to Enable Theranostic Alpha Particle Radiotherapeutic Agents

Award Number: R56EB029259
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/05/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Chelators to Enable Theranostic Alpha Particle Radiotherapeutic Agents - PROJECT SUMMARY Targeted internal radionuclide therapy is a highly efficacious form of cancer treatment that employs administered radiopharmaceutical agents to destroy malignant cells. Radiopharmaceutical agents of this type require a biological targeting vector, which selectively recognizes and binds to receptors that are overexpressed on cancer cells, and a bifunctional chelating agent, which stably binds to and attaches the radionuclide to the targeting vector. The radionuclide can be chosen and altered to possess different nuclear decay properties, potentially rendering it valuable for theranostic applications, as long as its coordination chemistry is compatible with the bifunctional chelator. Conventionally, beta particle emitters have been leveraged for therapeutic applications, but recent clinical studies have revealed the efficacious nature of alpha particle emitters for this application. The use of alpha emitters is hindered, however, by a lack of gamma photon or positron emissions that can be leveraged for theranostic applications and by their unconventional coordination chemistries, making it challenging to find a suitable bifunctional chelator. This project will address both of these challenges in alpha particle emitter targeted internal therapy by designing new bifunctional chelators that can be simultaneously used with diagnostic gamma- or positron-emitting radionuclides. In Specific Aim 1, new bifunctional chelators for the established highly promising alpha emitter actinium-225 will be developed. These chelators will be designed so that they can also effectively accommodate the widely available imaging radionuclide indium-111. With these new chelators, theranostic agents based on actinium- 225 can be easily accessed. Specific Aim 2 will focus on the short-lived alpha emitters lead-212 and bismuth- 213. To make theranostic agents from these radionuclides, bifunctional chelators that can be easily functionalized with the versatile positron-imaging radionuclide fluorine-18 will be synthesized. Lastly, in Specific Aim 3, chelators for the unconventional newly arising radionuclides uranium-230, and vanadium-48 will be developed. Uranium-230 is a therapeutic alpha emitter and vanadium-48 is a diagnostic positron emitter. We will explore chelating agents that are mutually compatible for these radiometals to enable their use as a theranostic pair. Through these three aims, this work will increase the diversity of radionuclides with distinct half-lives and decay chains that can be used for this application. Furthermore, it will give rise to diagnostic partners for these therapeutic alpha emitters, which is critically important for predicting patient dosimetry, disease staging, and response. Collectively, the successful execution of this project will give rise to theranostic alpha-emitting therapeutic agents that can cure and diagnose human disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $21,590 )
2025	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	1/10/2025	COMPETING CONTINUATION	-$326,614
2025	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	5	5/20/2025	COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	6	1/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$348,204
														Subtotal = $21,590

Issue Date FY: 2024 ( Subtotal = $714,409 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	5	7/24/2024	COMPETING CONTINUATION	$203,829
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	11/29/2023	COMPETING CONTINUATION	$510,580
														Subtotal = $714,409

Grand Total All Awards = $735,999

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Chelators to Enable Theranostic Alpha Particle Radiotherapeutic Agents

Award Number: R56EB029259

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/05/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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