David M. Long

Hemodynamic effects of intravenous lecithin-based perfluorocarbon emulsions in dogs.

We evaluated and compared the acute hemodynamic effects of perfluorooctylbromide-100% (PFOB), a fluorocarbon emulsified in lecithin without pluronic-F68 (F68), to those of a standard iodinated contrast agent, renografin-76% (R76), and Fluosol-DA 20% (Fluosol), a fluorocarbon emulsified in part by F68. Five open chest dogs were instrumented to evaluate hemodynamic changes after iv injection of PFOB (1 ml.1 g/kg) and R76 (1 ml.0.37 g of iodine/kg). Fluosol (1 ml.0.2 g/kg) was given to two of the five dogs at the end of their study. Fluosol caused transient hemodynamic collapse in both dogs. R76 caused the known transient effect of hypotension (-15.4 +/- 3.3%) followed by hypertension (6.5 +/- 2.7%) and an increase in aortic flow (29.3 +/- 3.9% at 30 sec). PFOB caused minimal, clinically insignificant decrease in aortic flow (4 +/- 1% at 10 sec).

Perfluoroctylbromide as a blood pool contrast agent for liver, spleen, and vascular imaging in computed tomography.

Perfluoroctylbromide (PFOB) in emulsion form was tested as a blood pool imaging agent for computed tomography (CT) in five animals (three dogs and two pigs). Computed tomography of the kidneys, liver, spleen, and mediastinum was performed in the control state and at various time intervals after the end of PFOB infusion. The attenuation coefficient of the vascular space increased by 117 Hounsfield units (HU) (range 105–128 HU), the liver by 54 HU (range 43–70 HU), and the spleen by 77 HU (range 69–86 HU) 30 to 50 min after the end of PFOB infusion, 5 ml/kg. The vascular space enhanced by 25 HU for every g of PFOB/100 ml of blood and remained at almost a constant level for hours after the end of infusion. In conclusion, PFOB emulsion, in addition to hepatosplenic enhancement, produces prolonged and substantial opacification of the vascular space, allowing CT imaging of the heart and vascular structures minutes to hours after the end of infusion.

Perfluorochemicals as liver- and spleen-seeking ultrasound contrast agents.

In this study, Fluosol‐DA, 20 per cent (composed of perfluorodecalin and perfluorotripropylamine) was tested as a liver‐specific ultrasound contrast agent. Twelve normal rabbits were scanned, utilizing the Picker Microview (10 MHz), prior to and two days following the intravenous administration of 24 ml/kg of Fluosol (or 4.8 g/kg of perfluorochemicals) emulsion to ten of the rabbits and 24 ml/kg of Ringers solution to two rabbits as control. In all ten rabbits given Fluosol, liver echogenicity increased relative to that of the kidney, whereas the liver remained less echogenic than the kidney in the two rabbits given Ringers solution. Four independent reviewers correctly identified all rabbits that received Fluosol and both rabbits that received Ringers solution. It is demonstrated that, similar to PFOB, Fluosol serves as an echogenic contrast material for ultrasound and opacifies the normal rabbit liver.

Experiments with radiopaque perfluorocarbon emulsions for selective opacification of organs and total body angiography.

Emulsions of radiopaque perfluorocarbon with small particle size were prepared by sonication and concentrated by centrifugation. The emulsions were well tolerated when given intravenously to rats in a dose up to 20 ml/kg. Whole-body angiograms were obtained for up to 6 hours after injection with visualization of vessels smaller then 1 mm. Hepatosplenograms were obtained after 2 hours and for several days after injections of radiopaque perfluorocarbon. Contrast enhancement was also seen in the myocardium, ovaries, adrenal glands, and intestines with brominated perfluorocarbon emulsions.

CT determination of renal and hepatic microvascular volumes in experimental acute renal failure.

Alterations in renal blood flow are considered to play an important role in the pathogenesis of acute renal failure. Most techniques designed to assess organ blood flow and microcirculatory disturbances are relatively invasive and cumbersome. This study describes a noninvasive method for the determination of an organs fractional vascular volume (FVV)-the fraction of an organ occupied by blood vessel lumen. It utilizes computed tomographic (CT) scanning and a contrast agent, perfluoroctylbromide (PFOB), which remains intravascular and is not excreted by the kidney. Acute renal failure (ARF) was induced in rats by intraperitoneal injection of glycerol (5 g/kg). CT scans of kidneys, liver, and heart were performed prior to and following intravenous administration of PFOB. FVV of kidney and liver were calculated prior to induction of ARF and at selected time periods following ARF (20-50 minutes and 60-120 minutes). FVV of the kidney decreased significantly 20-50 minutes following ARF and had returned to control values at 60-120 minutes. Renal histologic abnormalities were more severe at the later time period. Thus, early alterations in blood flow precede pathologic abnormalities in the kidney following glycerol-induced ARF. Determination of an organs fractional vascular volume is a simple noninvasive technique which provides useful information on the microcirculation during the course of experimental disease.

New high O2 carrying perfluorochemical emulsions: Toxicity, radiosensitivity of GM-CFC and development of metastases in mice

The effects of two new concentrated perfluorochemical emulsions based on F-66E and PFOB, which carry significantly more oxygen than Fluosol-DA 20%, were tested on normal tissues (toxicity and radiation response) and on the development of metastases from Lewis Lung Carcinoma (3LL) in female C57 BL/6 mice. Twenty one days after injection of F-66E or PFOB emulsions (15 ml/kg body weight), the spleen and liver weights were significantly increased but had returned to normal after 2-3 months. Splenomegaly already observed in 3LL bearing mice was significantly increased by F-66E emulsion injection. The radiosensitivity of GM-CFC was not altered when unanesthetized GM-CFC was not altered when unanesthetized mice were pretreated with F-66E emulsions and/or carbogen 1 hr prior to and during irradiation. The rate of tumor take and the period before detection of tumors were not modified when an emulsion of F-66E was injected simultaneously or 10 days after 3LL cells. Mean survival of mice, and the number of metastases on lung surfaces were similar in F-66E injected mice and control mice.

Biological disposition of perfluoroctylbromide: tracheal administration in alveolography and bronchography.

Perfluoroctylbromide, given tracheally either as neat liquid in alveolography or as 10:1 emulsion in bronchography, was cleared roentgenologically from the lungs within 24 hours. Quantitative analysis was performed on a gas chromatograph. The rats were given either 2 ml/kg of neat liquid or 0.4 ml/kg emulsion. One per cent of the neat liquid and 8% of the emulsion were recovered from the tissues respectively 24 hours later. The lungs had the largest amount followed by the intestine, adipose tissue and lymph nodes. Dogs were sacrificed at various intervals following 4 ml/kg of neat liquid or 2 ml/kg of emulsion. Less than 1% of the dose was found in the tissues at 24 hours. A similar pattern of perfluoroctylbromide distribution was observed as in the rats. The tissue contents of perfluoroctylbromide at three months were below the limit of detection. The perfluoroctylbromide levels in the blood and urine of dogs and human volunteers were either non-detectable or barely detectable over a 48-hour period.

SPECIFIC ENHANCEMENT OF INTRA-ABDOMINAL ABSCESSES WITH PERFLUOROCTYLBROMIDE FOR CT IMAGING

Perfluoroctylbromide (PFOB), a radiopaque reticuloendothelial system contrast media for computed tomography, has been shown to accumulate in macrophages. In the current study PFOB was tested in rabbits as an abscess imaging agent. Two abscesses were induced in each of 24 rabbits, one in the liver and the other in the peritoneal cavity. CT of the rabbit abdomen was performed four days later, two days after the administration of 5 gm/Kg of PFOB to 12 of these rabbits. The average enhancement of the wall of liver abscesses was by 140 Hounsfield units (HU) relative to the enhanced liver and peritoneal abscesses by 135 HU relative to the control group. This enhancement was secondary to the intense accumulation of PFOB filled macrophages in the abscess wall. In those rabbits where the liver abscess ruptured, the edges of the peritoneal collections enhanced by 147 HU. Regions of inflammation prior to liquifaction enhanced considerably. These areas could not be detected in the animals not receiving PFOB. Though the liquified center of liver abscesses could be seen in the absence of PFOB, none of the peritoneal abscesses could be detected in the animals not receiving PFOB. In contradistinction, all peritoneal abscesses enhanced considerably following PFOB allowing their prospective localization. In conclusion, PFOB accumulates in abscess walls and areas of inflammation producing marked CT enhancement of liver and peritoneal abscess collections. This enhancement allowed the differentiation of peritoneal abscess collections from adjacent bowel.

Dose Related Biodistribution & Elimination of 100% PFOB Emulsion

Perfluoroctylbromide (PFOB) has been applied successfully as an oxygen carrier and a contrast agent for X-ray, computed tomography, ultrasound and Magnetic Resonance Imaging (MRI). Knowledge of the pharmacokinetics of emulsion particle uptake and elimination is critical for determining proper dose and timing of diagnostic studies. This study was intended to define major organ biodistribution and half-life as well as total body half-life as a function of dose.Determination of biodistribution and major organ half-life was achieved by administering 100% PFOB emulsion intravenously to 180 rats divided into 3 dose groups of 0.3, 0.6 & 1.0 g/kg. Each group was divided into 6 subgroups (n = 10; S male and 5 female). Each subgroup was sacrificed at either 6 or 90 min., 1,2,7, or 28 days post injection. 16 different tissue samples were collected and PFOB concentration determined by iso-octane extraction and gas chromatographic (GC) analysis. Total body half-life was determined by administering PFOB intravenously t...

Comparison of Radiopaque Perfluorocarbon and Ethiodoi in Lymphography

Lymphangiography was performed on 40 adult cats, 39 dogs, 20 rabbits, and 12 rats of mixed sex using Ethiodol or radiopaque perfluorocarbon (BPC). Ethiodol was more radiodense than RPC, but imaging of lymph channels and nodes was satisfactory with the latter. RPC could be infused rapidly, while Ethiodol infusion was time consuming. RPC was biologically inert; Ethiodol produced both local and systemic inflammatory reactions. The lymph node distribution with RPC was more uniform and persisted for longer periods. It was concluded that RPC was an improvement over Ethiodol for lymphangiography.