We have shown that perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents whose echogenic effect on the liver, spleen, and tumors in animals and man, was detectable by standard US equipment. We also showed that perfluoroctylbromide (PFOB), a radiopaque PFC enhanced the vascular space, liver, spleen, renal osmotic gradient, and macrophage collections on computed tomography (CT). Very stable 100% w/v PFOB emulsion has been produced with lecithin alone. PFOB has been approved for intravenous use in Europe 15 patients have been studied (up to 2.5g/kg) with no side effect attributable to PFOB. We hope to have FDA approval in the U.S.A. by late 1987. PFC concentration (()) in tissues can only be measured with gas chromatography (GC) of tissue extracts. While GC is sensitive and specific to PFC, the % extracted is unknown. Bromine in PFOB, is detectable by Neutron Activation Analysis (NAA). It showed that extraction was less than 50%, varied for different organs, and decreased over time for the same organ biasing pharmacokynetics data. We wish to utilize NAA to evaluate the efficacy of several extraction techniques to optimize our extraction, correct our data, explain discrepancies between CT and tissue (PFOB), and since this problem is not unique to PFOB, provide data to those that must utilize extracts. Seeking a technique to estimate (PFOB) in vivo which allows for longitudinal studies and tissue (PFOB) mapping, we constructed a small CT phantom which was calibrated, and validated for (PFOB) up to 70mg/g. (PFOB) determined with CT and high correlation with NAA (Y-1.01X-4, r-0.96). We propose to calibrate the phantom to higher (PFOB), test its accuracy in assessing biodistribution and elimination in live rabbits, and construct, calibrate, and validate a larger phantom for human use. The delayed echogenic effect of PFC's (24-48hrs) is thought to be impractical. We have recently observed that PFOB enhances tissues within minutes after infusion. We wish to prove this observation by comparing relative echogenicity of a vascular tissue (renal cortex and liver) to a relatively hypovascular tissues (Vx2 tumor), as well as an implanted phantom over time and at different PFOB dosages (1-5g/kg). We showed in vitro utilizing PFOB and its vehicle emulsion that PFOB is a potent additive to a lecithin emulsion that markedly affects acoustic properties at 5MHz. We wish to extend these experiments to other frequencies and to tissues to better understand the mechanisms of PFOB tissue enhancement.

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National Cancer Institute (NCI)
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University of California San Diego
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