In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

In vivo deuterated water ((H2O)-H-2) labeling leads to deuterium (H-2) incorporation into biomolecules of proliferating cells and provides the basis for its use in cell kinetics research. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with H-2 and, therefore, could be visualized by deuterium magnetic resonance imaging (dMRI) following a brief period of in vivo systemic (H2O)-H-2 administration. We initiated systemic (H2O)-H-2 administration in two xenograft mouse models harboring either human colorectal, HT-29, or pancreatic, MiaPaCa-2, tumors and (H2O)-H-2 level of similar to 8% in total body water (TBW). Three schemas of (H2O)-H-2 administration were tested: (1) starting at tumor seeding and continuing for 7 days of in vivo growth with imaging on day 7, (2) starting at tumor seeding and continuing for 14 days of in vivo growth with imaging on day 14, and (3) initiation of labeling following a week of in vivo tumor growth and continuing until imaging was performed on day 14. Deuterium chemical shift imaging of the tumor bearing limb and contralateral control was performed on either day 7 of 14 after tumor seeding, as described. After 14 days of in vivo tumor growth and 7 days of systemic labeling with (H2O)-H-2, a clear deuterium contrast was demonstrated between the xenografts and normal tissue. Labeling in the second week after tumor implantation afforded the highest contrast between neoplastic and healthy tissue in both models. Systemic labeling with (H2O)-H-2 can be used to create imaging contrast between tumor and healthy issue, providing a non-radioactive method for in vivo cancer imaging.