CARBON-COATED PREPARATIONS WITH MIXED AU198 AND AG111 ISOTOPES FOR MEDICAL USE.
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The influence has been investigated of particle size on the uptake of radioactive gold colloid by the rabbit thoracic aorta perfused in situ. Particles ranging in diameter from 14 nm to 40 nm were suspended in 0.9% NaCl and infused either at a pressure of 15 mm Hg for times of between 2 1/2 and 60 min or at pressure of between 15 and 160 mm Hg for 5 min. Uptake by the whole intima-media increased with perfusion time and hydrostatic pressure but did not depend on particle size. Radioactive assay of serial sections across the aortic wall also showed that particle size did not influence the distribution of tracer. An effect of perfusate composition on uptake was demonstrated in further experiments in which particles either 14 or 40 nm in diameter were suspended in pooled rabbit serum and infused at pressures of between 15 and 140 mm Hg for 5 min. Uptake and transmural distribution were again independent of particle size, but uptake was 4-5-fold less than when the particles were perfused in saline. Under all perfusion conditions radioactivity fell steeply across the intima and then rose gradually across the media and adventitia. Radioactivity in the outer media and adventitia increased with perfusion time but little change could be detected in intimal activity. In transmission electron micrographs, particles in the intima were not seen to penetrate the internal elastic lamella and in the outer media particles remained extracellular and did not enter collagen bundles. Autoradiographs showed that particles in the intima were uniformly distributed around the circumference of the vessel but in the outer media and adventitia particles usually clustered close to the vasa vasorum.
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Since 1972, telecobalt irradiation plus intrathecal methotrexate (ITMTX) has been successfully replaced in Jena by intrathecal colloidal radioactive gold (198Au) plus ITMTX for meningosis prophylaxis in leukemia. Seventy-three children with acute lymphocytic leukemia (ALL) were given 1.24-4.89 mCi (45.8-181 MBq) of colloidal 198Au IT after successful initiation of remission. During cytostatic therapy, the following relapses occurred: meningosis leucaemica, five patients (6.8%); bone-marrow relapse and the meningosis leucaemica, one patient; and bone-marrow relapse, 20 patients (27.4%). In 18 children, combination chemotherapy was terminated after two and a half or three years of treatment. After that time, one meningeal relapse and six bone-marrow relapses occurred. Within the first 24 hours after application of radioactive gold, headaches, vomiting, and fever occurred in less than 10% of the children. An apathy syndrome, leukecephalopathy, or severe infections, were not observed in a single case. Radioactive gold spreads in the subarachnoid space and is phagocytized by the arachnoidea. The tumoricide effect extends selectively over the space of distribution of the latent meningosis leucaemia. The cerebral parenchyma remains unaffected by radiation. Thus, radioactive gold may be preferable to telecobalt irradiation in preventing central nervous system leukemia.