Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging

Brittany A. Broder; Mohammed Bhuiyan; Richard Freifelder; David A. Rotsch; Satish K. Chitneni; Marvin W. Makinen; Chin Tu Chen

doi:10.3390/molecules29040799

Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging

Brittany A. Broder
, Mohammed Bhuiyan
, Richard Freifelder
, David A. Rotsch
, Satish K. Chitneni
, Marvin W. Makinen
, Chin Tu Chen

Medical Isotopes and Development

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)₂], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (⁴⁸V) generated with a compact medical cyclotron has been used to label VO(acac)₂ as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)₂ require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)₂, [⁴⁸V]VO(acac)₂, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [⁴⁸V]VO(acac)₂. Preliminary results of preclinical, small-animal PET studies are presented.

Original language	English
Article number	799
Journal	Molecules
Volume	29
Issue number	4
DOIs	https://doi.org/10.3390/molecules29040799
State	Published - Feb 2024

Funding

This project was supported in part by the NIH Cancer Center Support Grant (#P30 CA14599) to the University of Chicago Comprehensive Cancer Center; the Pilot Seed Grant funding provided by the Department of Radiology at the University of Chicago and its Hodges Society; and by the Graduate Fellowship in STEM Diversity as part of the GFSD Fellowship. We are grateful for continuous support from The University of Chicago Cyclotron Facility and the Integrated Small Animal Imaging Research Resource (iSAIRR). We want to especially thank Lara Leoni, Aaron Hsiu-Ming Tsai, and Erica Markiewicz for their invaluable contributions to the animal imaging and biodistribution studies.

Keywords

high performance liquid chromatography (HPLC)
PET imaging
positron emission tomography (PET)
radioactivity
vanadium
vanadium-48
vanadyl acetylacetonate

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title = "Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging",

abstract = "Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.",

keywords = "high performance liquid chromatography (HPLC), PET imaging, positron emission tomography (PET), radioactivity, vanadium, vanadium-48, vanadyl acetylacetonate",

author = "Broder, \{Brittany A.\} and Mohammed Bhuiyan and Richard Freifelder and Rotsch, \{David A.\} and Chitneni, \{Satish K.\} and Makinen, \{Marvin W.\} and Chen, \{Chin Tu\}",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

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doi = "10.3390/molecules29040799",

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volume = "29",

journal = "Molecules",

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T1 - Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging

AU - Broder, Brittany A.

AU - Bhuiyan, Mohammed

AU - Freifelder, Richard

AU - Rotsch, David A.

AU - Chitneni, Satish K.

AU - Makinen, Marvin W.

AU - Chen, Chin Tu

PY - 2024/2

Y1 - 2024/2

N2 - Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.

AB - Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.

KW - high performance liquid chromatography (HPLC)

KW - PET imaging

KW - positron emission tomography (PET)

KW - radioactivity

KW - vanadium

KW - vanadium-48

KW - vanadyl acetylacetonate

UR - https://www.scopus.com/pages/publications/85185897934

U2 - 10.3390/molecules29040799

DO - 10.3390/molecules29040799

M3 - Article

C2 - 38398551

AN - SCOPUS:85185897934

SN - 1420-3049

VL - 29

JO - Molecules

JF - Molecules

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M1 - 799

ER -

Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging

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