Rapid in vivo monitoring of chemotherapeutic response using weighted sodium magnetic resonance imaging

A novel pulse sequence strategy uses sodium magnetic resonance imaging to m onitor the response to chemotherapy of mouse xenograft tumors propagated fr om human prostate cancer cell lines. An inversion pulse suppresses sodium w ith long longitudinal relaxation times, weighting the image toward intracel lular sodium nuclei, Comparing these weighted sodium images before and 24 h after administration of antineoplastics, we measured a 36 +/- 4% (P < 0.00 1; n = 16) increase in signal intensity. Experiments with these same drugs and cells, treated in culture, detected a significant intracellular sodium elevation (10-20 mM) using a ratiometric fluorescent dye. Flow cytometry st udies showed that this elevation preceded cell death by apoptosis, as deter mined by fluorescent end-labeling of apoptotic nuclei or Annexin V binding. Histopathology on formalin-fixed sections of explanted tumors confirmed th at drug administration reduces proliferation (2.2 versus 8.6 mitotic figure s per high power field; P < 0.0001), an effect that inversely correlates wi th the sodium magnetic resonance image response on a tumor-to-tumor basis ( P < 0.02; n = 10), Morphological features, such as central zones of nonviab le cells, rims of active apoptosis, and areas of viable tumor, could be dis tinguished by comparing weighted and unweighted images. Advantages of this sodium imaging technique include rapid determination of drug efficacy, impr oved diagnosis of lesions, ease of coregistration with high resolution prot on magnetic resonance imaging, and absence of costly or toxic reagents.