FLUORINE -19 NMR-SPECTROSCOPY FOR MEASURI NG INDUCED CHANGES IN BLOODPERFUSION VOLUME IN EXPERIMENTAL-TUMORS IN-VIVO

The biological response of some anti-cancer therapeutic, agents is pro bably mediated via the tumour vasculature. A novel approach using F-19 NMR spectroscopy in vivo has been developed to directly measure chang es in vascular perfusion volume in experimental tumours. A 100% w/v pe rfluorooctylebromide (PFOB) emulsion was used as a tracer. For a fixed position of a 7 mm surface coil placed over the tumour, the signal fr om the PFOB rapidly reached an equilibrium value remaining unchanged f or at kast 2 hours. Since the strength of the fluorine signal is direc tly proportional to the perfusion volume of the tumour vasculature, re duction of signal intensity should correspond directly to any reductio n in volume which may be a manifestation of a change in the tumour blo od flow. This hypothesis was investigated using hydralazine as a physi ological modifier of tumour blood flow. Administration of 5 mg/kg of h ydralazine following dosing with the PFOB emulsion reduced the F-19 si gnal intensity from the murine tumors RIF-1 and KHT and from the human tumour HT29 with no or little reduction in the SCCVII/Ha murine and H X118 human tumours. Changes in blood volume in KHT tumour accompanied local changes in tumour blood flow rate as measured by the Xe-133 clea rance rate technique. Thus, these data demonstrate the potential of th e PFOB emulsion as a F-19 NMR tracer of the vasculature to measure cha nges induced by therapeutic agents on blood volume in accessible tumou rs. This method may also be useful to detect early changes in blood vo lume produced during angiogenesis of solid tumours or angiostatic acti vity of anti-cancer drugs.