For the past 5 years the P.I., under the supervision of Drs Higgins, Lasser, and Berk, has been engaged in research aimed at defining risk and benefits of perfluorotylbromide (PFOB), a radiopaque perfluorocarbon (PFC). While toxicity is minimal, many benefits have been uncovered. The most notable are: 1) blood pool, liver/spleen, and tumor enhancement rendering PFOB the most ideal CT contrast agent; 2) the discovery that PFC's are effective ultrasound contrast agents producing persistent liver and spleen enhancement in animals and man; and 3) the discovery that PFC's, because they lack hydrogen (H) emit no signal at H resonance serving as ideal oral contrast agents in animals and man. The proposed projects planned for the next 5 years utilizing PFOB, will not only serve for the growth and development of the P.I.'s research career, but also for the introduction of key CT, ultrasoound, and MRI applications to patient care. The non- clinical projects are: 1) development of a CT phantom to determine PFOB biodistribution and elimination in man non- invasively; 2) proof that PFOB enhances tissues on ultrasound minutes post infusion; and 3) development of PFOB as an in vivo oxygen (02) probe to measure tissue p02. This is possible since PFOB has 17 fluorine (F) atoms and F T1 is shortened by the dissolved 02. This is a new, exciting, and potentially important horizon. We believe that with localized spectroscopy, tissue p02 can be measured in man since there will be sufficient signal at the expected human diagnostic dose of 1.5g (1.5ml)/kg for T1 measurement. Stable PFOB emulsion at 100% w/v (1g in 1ml) has been produced with lecithin alone. Thus formulation has been approved for intravenous use by the National Drugs Advisory Board in Ireland and the IRB at St. Vincent's hospital, in Dublin, where trials will begin February 1987. Clinical trials at UCSD are planned for late 1987. Since the expected human diagnositic dose of 1.5g (or 1.5ml)/kg causes no detectable toxicity in animals, and since the LD50 in mice is 45g/kg, it potential impact on clinical imaging is significant and imminent.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA001319-04
Application #
3071829
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1988-05-01
Project End
1993-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Andre, M; Nelson, T; Mattrey, R (1990) Physical and acoustical properties of perfluorooctylbromide, an ultrasound contrast agent. Invest Radiol 25:983-7