Direct arterial injection of hyperpolarized compounds into tumor tissue enables rapid detection of metabolism with minimal dilution
Steven Reynolds1, Stephen Metcalf2, Rebecca Collins3, Edward Cochrane3, Simon Jones3, Martyn Paley1, and Gillian Tozer2
1Academic unit of radiology, University of Sheffield, Sheffield, United Kingdom, 2Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom, 3Department of Chemistry, University of Sheffield, Sheffield, United Kingdom
Hyperpolarizing drug candidates could allow insights into their mode of
action and metabolic fate. However, administering drug molecules at high
concentrations can lead to adverse effects in animals. We have developed a
method for directly administering substrates to tumor tissue by infusion
through a single supplying artery, thus maximizing tumor drug delivery and
minimizing T1 relaxation and systemic toxicity. The net signal gain for arterially
injected 13C-pyruvate was x54, compared with the systemically
administered venous route. Hyperpolarized custom 13C-labeled CA1 was
arterially administered and its parent peak observed, in vivo, at its expected chemical shift (58ppm).
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