Abstract
Following radiation therapy (RT), tumor morphology may remain unchanged for days and sometimes weeks, rendering anatomical imaging methods inadequate for early detection of therapeutic response. Changes in the hyperpolarized [1-13C]lactate signals observed in vivo following injection of pre-polarized [1-13C]pyruvate has recently been shown to be a marker for tumor progression or early treatment response. In this study, the feasibility of using 13C metabolic imaging with [1-13C]pyruvate to detect early radiation treatment response in a breast cancer xenograft model was demonstrated in vivo and in vitro. Significant decreases in hyperpolarized [1-13C]lactate relative to [1-13C]pyruvate were observed in MDA-MB-231 tumors 96 hrs following a single dose of ionizing radiation. Histopathologic data from the treated tumors showed higher cellular apoptosis and senescence; and changes in the expression of membrane monocarboxylate transporters and lactate dehydrogenase B were also observed. Hyperpolarized 13C metabolic imaging may be a promising new tool to develop novel and adaptive therapeutic regimens for patients undergoing RT.
Highlights
Accurate and non-invasive assessment of tumor response following radiation and/or chemotherapy is crucial for patient management and development of novel therapeutic regimens
Radiation treatment planning and evaluation of tumor response are performed by anatomical imaging methods such as CT and MR imaging
Hyperpolarized [1-13C]lactate and [1-13C]pyruvate signals were observed in the tumors following injections of pre-polarized [1-13C]pyruvate in the rat MDA-MB-231 xenograft model (Fig. 1)
Summary
Accurate and non-invasive assessment of tumor response following radiation and/or chemotherapy is crucial for patient management and development of novel therapeutic regimens. PET has been utilized in recent years to detect changes in tumor glucose or amino acid metabolism, oxygenation, and proliferation following treatment [1,2,3], it is often not performed early post treatment due to confounding effects of inflammation and negative predictive values in some cancers. It is not clear PET would be helpful for the recent developments of hypofractionated, and adaptive RT regimens [4,5]. There is the risk of excessive radiation exposure with PET-CT scans if used for repeated follow up
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