This project's goal is to complete a comprehensive study of the biologic mechanisms involved in the use of Perfluoroctylbromide (FOB) for diagnostic imaging of inflammatory lesions. These lesions include malignant tumors, abscesses and infarcts. Stable emulsions of FOB have been successfully prepared with low acute and chronic toxicity. FOB imaging of reticuloendothelial organs such as the liver and spleen in addition to inflammatory lesions is due to the presence of macrophages laden with FOB particles of this emulsion. The mechanisms and patterns of macrophage proliferation will be studied; in addition the effects of hormones, surface active agents and immunoactive drugs will be explored in detail. These hormones, drugs and agents will be used to modulate and control targeted FOB laden macrophages to facilitate uptake of FOB by lesions. Thus, the effective dose and cost of FOB will be reduced. Second-generation emulsion formulations will be designed and tested. Improvement in formulation will be made through the use of modern emulsifying equipment and stabilizing agents. These improvements will produce uniformly smaller emulsion particles and thus prolong intravascular dwell time, increase uptake by inflammatory lesions and decrease the total body half-life of FOB. Excess emulsifier will be used to prolong intravascular dwell times and accelerate excretion of FOB without compromising the capacity to image lesions and organs. The effects of FOB and emulsifier on blood pool imaging will be documented radiographically and chemically and hemodynamic effects will be studied. Repeated large doses of fluorocarbon emulsions produce an unusual side effect of temporary delayed anemia. All facets of the side effects of fluorocarbon emulsions will be examined, even though they may not apply to diagnostic dose levels. Earlier diagnosis of malignant tumors is essential to improve cure rates. The sensitivity of CT and ultrasound imaging is improved by an order of magnitude using FOB contrast enhancement of inflammatory lesions so that lesions less than 5mm can be imaged. Contrast enhancement of Nuclear Magnetic Imaging with 19F and fluorocarbons is controversial. This issue will be resolved in this laboratory with proven capacity for preparing safe and effective fluorocarbon emulsions for diagnostic purposes.
