The pharmacokinetics and applicability of aerosol amphotericin B administrations were studied in 40 neutropenic patients and 4 healthy volunteers. Particle size was measured and pulmonary deposition was demonstrated by radioisotope studies. Inhalations were easy to administer and were well tolerated, with minimal systemic absorption of the drug.Invasive pulmonary aspergillosis (IPA) is a serious fungal infection in immunocompromised or neutropenic patients (3). The incidence of and mortality from IPA vary depending on the degree and duration of immunosuppression or neutropenia. After bone marrow transplantation (BMT), mortality can be as high as 95% (3, 12). Various strategies for systemic or topical prophylaxis of IPA have been developed (4,6,8,13,14,16,17), but they are still unsatisfactory (1,5,18). The use of aerosol amphotericin B (aeroAmB) is a promising approach. In a rat model, aeroAmB was effective as prophylaxis for IPA (15), and high concentrations of amphotericin B (AmB) were achieved in the lung tissues of these animals (10). Prophylactic aeroAinB has been used successfully in neutropenic patients, but little is known about the distribution and pharmacokinetics of aeroAmB in humans (2, 9). The goals of the present study were to determine the particle size, organ distribution, and pharmacokinetics of aeroAmB and to evaluate its clinical applicability. At first, the particle size of aeroAmB was determined by using a Phase-Doppler-Particle-Analyser (Aerometrics, Mountain View, Calif.), which allowed noninterfering optical measurements of individual particles at a size range of 0.53 to 18.5 ,um. For the measurements 10 mg of the AmB preparation for intravenous administration (Squibb, Munich, Federal Republic of Germany) were diluted with sterile water to a total volume of 5 ml and were placed into a RespirGard II nebulizer (Marquest, Englewood, Colo.). An air pressure of 1.8 x 105 Pa was used to drive the nebulizer, and particle sizes were measured at the mouthpiece of the device. A narrow particle size distribution was demonstrated, with a mean diameter of 2.6 ,um; 10% of the particles had a diameter of less than 0.9 ,um and 90% had a diameter of less than 4.2 ,um. The mass median diameter was 4.8 pum (Fig. 1)

Invasive pulmonary Aspergillus infections are increasingly recognized among severely neutropenic and/or immunosuppressed individuals. As the infections are usually acquired through the inhalation of Aspergillus conidia, at present prevention of invasive pulmonary aspergillosis consists mainly of the reduction of environmental exposure to aspergillus conidia. More recently, prophylaxis with amphotericin B aerosols has been investigated. Inhalations with amphotericin B aerosols significantly delayed mortality in an animal model of invasive pulmonary aspergillosis and high pulmonary concentrations of amphotericin B could be achieved. In man, pulmonary deposition of amphotericin B could also be demonstrated using commercially available nebulizers. Inhalations were well tolerated with little systemic absorption of the drug. In order to evaluate the efficacy of aerosol amphotericin B administrations for the prevention of invasive pulmonary aspergillosis, a prospective randomized trial has been initiated.

Radioimmunoscintigraphy (RIS) with 131I labeled OC-125 F(ab')2 monoclonal antibody fragments was prospectively studied in 43 women for primary diagnosis and follow up of ovarian cancer. Total body planar photoscans with a scintillation camera were performed one to seven days after antibody application and results were compared with operation and or CT examination. By the region of interest technique the tumor to non tumor tissue ratio (T/N) was calculated in vivo. Sensitivity in primary diagnosis was 100% (10/10), specificity 33% (1/3). For local recurrency, sensitivity was 86% (19/22), for metastatic loci 80% (17/21). Specificity was 75% and 50%. T/N ratio was in the rage from 1.3 to 2.8. Sensitivity for ovarian cancer is high in primary diagnosis and follow up. By the region of interest technique it is possible to detect small recurrencies and to presume peritoneal carcinosis. Antibody accumulations in diseases different from ovarian cancer however diminish specificity.

An alteration of the dopaminergic nigrostriatal system is believed to be the main pathogenetic factor of Parkinson's disease (PD). We report on our initial results on the determination of the post-synaptic dopamine-D2-receptor binding of 123I-IBZM in patients with PD. Drug-native patients showed a significantly higher IBZM binding in the basal ganglia as compared to patients on specific dopaminergic medication. Age, duration of the disease and the severity of the disease do not seem to influence the IBZM-receptor binding. We conclude that 123I-IBZM-SPECT is an extremely useful tool for the evaluation of the functional state of cerebral dopamine-D2-receptors.

In this prospective study the diagnostic merit of radioimmunoscintigraphy (RIS) was compared with computed tomography (CT) and operation in the primary diagnostic procedure and follow-up of women with suspected ovarian cancer. In primary diagnosis, sensitivity, specificity, and diagnostic accuracy was 100%, 60% and 90% for RIS. In follow-up, sensitivity for local recurrence was slightly higher in CT than in RIS. It was possible to detect peritoneal carcinosis in the pelvis and lower abdominal region better with RIS, but in the upper abdominal region, peritoneal carcinosis was detected better with CT. If no differentiation between benign or malignant lesion, is possible with CT, differentiation will in many cases be possible with RIS.