Authors: Devkumar Mustafi Bo Peng Sean Foxley Marvin W Makinen Gregory S Karczmar Marta Zamora John Ejnik Heather Martin
Publish Date: 2009/07/02
Volume: 14, Issue: 8, Pages: 1187-
Abstract
We have developed a magnetic resonance imaging MRI method for improved detection of cancer with a new class of cancerspecific contrast agents containing vanadyl VO2+chelated organic ligands specifically bisacetylacetonatooxovanadiumIV VOacac2 Vanadyl compounds have been found to accumulate within cells where they interact with intracellular glycolytic enzymes Aggressive cancers are metabolically active and highly glycolytic an MRI contrast agent that enters cells with high glycolytic activity could provide highresolution functional images of tumor boundaries and internal structure which cannot be achieved by conventional contrast agents The present work demonstrates properties of VOacac2 that may give it excellent specificity for cancer detection A high dose of VOacac2 did not cause any acute or shortterm adverse reactions in murine subjects Calorimetry and spectrofluorometric methods demonstrate that VOacac2 is a blood pool agent that binds to serum albumin with a dissociation constant K d ~ 25 ± 07 × 10−7 M and a binding stoichiometry n = 103 ± 004 Owing to its prolonged blood halflife and selective leakage from hyperpermeable tumor vasculature a low dose of VOacac2 015 mmol/kg selectively enhanced in vivo magnetic resonance images of tumors providing highresolution images of their interior structure The kinetics of uptake and washout are consistent with the hypothesis that VOacac2 preferentially accumulates in cancer cells Although VOacac2 has a lower relaxivity than gadoliniumbased MRI contrast agents its specificity for highly glycolytic cells may lead to an innovative approach to cancer detection since it has the potential to produce MRI contrast agents that are nontoxic and highly sensitive to cancer metabolism
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