Robert M. Donati

Evaluation of 99mTc-Pyrophosphate as a Bone Imaging Agent

A preliminary evaluation of the bone-localizing properties of 99mTc-pyrophosphate demonstrates favorable skeletal concentration, rapid blood and renal clearance, and ease of chemical reproducibility. The authors report the results of bone imaging with 99mTc-pyrophosphate for the detection of osseous metastases in 30 patients with known or suspected primary carcinoma.

67Ga Citrate Distribution Following Whole-Body Irradiation or Chemotherapy

Whole-body retention, organ distribution, excretion, and serum binding of 67Ga were evaluated in rats under normal conditions and following whole-body gamma irradiation, vincristine sulfate, or mechlorethamine. The results suggest that both irradiation and chemotherapy lead to reduced whole-body retention of injected radiogallium, explained in part by an alteration in the serum binding of gallium. Recognition of these findings should be considered in interpreting decreased tumor concentration of gallium in patients following radiotherapy or chemotherapy.

Mechanism of hepatic extraction of gelatinized 99mTechnetium sulfur colloid

Hepatic extraction, cellular and subcellular localization of gelatin stabilized Tc-99m sulfur colloid was studied in the rat model with time sequenced microautoradiography from 15 min to 24 h following I.V. administration of the tracer. Hepatic lobular and cellular distribution, quality and quantity of focal grain pattern, grain clusters, remained essentially constant for the period of study. Grain clusters were associated predominantly with Kupffer cells lining the peripheral segment of hepatic lobular sinusoids. Subcellular localization of gelatinized Tc sulfur colloid, stained prior to the I.V. administration with osmium tetroxide, was demonstrated with a transmission electron microscope in unosmicated liver tissue. Extracted Tc sulfur colloid particles were attached in groups to cytoplasmatic membranous intrasinusoidal projections of activated Kupffer cells. Intracytoplasmatic phagocytosis was not demonstrated. The kinetic arrest and en groupe extraction of Tc sulfur colloid particles at the Kupffer cell membrane suggests a specific membrane receptor site and specific Tc sulfur colloid particle-plasma protein interaction at the time of extraction. Hepatic extraction of gelatinized Tc sulfur colloid thus reflects primarily extra and intra hepatic hemodynamics and does not serve as an indicator of phagocytic hepatic reticuloendothelial system function.

Tropolone: A Lipid Solubilizing Agent for Cationic Metals

Lipid soluble agents which chelate radioactive cations have several potential uses in nuclear medicine including: brain imaging, labeling of blood elements, and identifying fatty infiltration of organs. A tropolone-gallium complex has been characterized by the determination of in vitro partition ratios correlated with in vivo organ distribution in the rat. Partition ratios were determined for gallium-67 citrate, indium-114m chloride, and iron-59 chloride cations complexed with tropolone in chloroform+water, octanol+water, olive oil+water, and olive oil+plasma two-phased systems. Tropolone proved to be highly effective in the lipid solubilization of these metal cations. Distribution studies in animals of these cations complexed with tropolone demonstrated an increased concentration of these cation complexes in tissues of high lipid content when compared with appropriate controls.

Erythropoiesis in hypothyroidism.

Summary The purpose of this study was to clarify the role which disordered iron metabolism and alterations in the homeostatic regulation of red cell production play in hypothyroid anemia. Following the measurement of the oxygen consumption, rats were thyroidectomized and given an ablative dose of sodium 131iodine. The oxygen consumption was again measured and the experiments initiated 8 weeks thereafter. The 18-hr red cell radioiron incorporation was used as an index of erythropoiesis. The gastrointestinal absorption of radioiron and the 24-hr urinary erythropoietin levels were assessed. Hypothyroid rats demonstrated a decreased red cell radioiron incorporation and a diminished GI iron absorption. The diminution in erythropoiesis was reverted toward normal by the administration of erythropoietin, D-triiodo-thyronine, L-triiodothyronine or exposure to hypobarbaric hypoxia. Erythropoietin, which completely corrected the erythropoietic depression in the hypothyroid rats, did not correct the decreased GI radioiron absorption whereas L-triiodothyronine restored both to normal. Urinary erythropoietin was decreased in the hypothyroid rat and reverted to normal following L-triiodothyronine administration. These data suggest that the mechanism producing the erythropoietic decompensation in hypothyroid states is complex and involves the lack of erythropoietic stimulation by erythropoietin. Acute erythropoietic compensation appears possible by the administration of nonspecific erythropoietic stimulants; however, the defect in gastrointestinal iron absorption can only be repaired by the administration of thyroid hormones.

67Ga Citrate in Renal Allograft Rejection

Eight renal allograft recipients were examined on 31 occasions following administration of 99mTc sulfur colloid and 67Ga citrate. Transplant accumulation of each agent was compared and collated with the clinical diagnosis. The procedures matched in 25 instances (81%). Gallium accumulated in the graft producing a false positive result in 2 instances of acute tubular necrosis with anuria, and failed to accumulate within the graft in one case of chronic rejection and in 2 instances of acute rejection. Both radioagents failed to accumulate in 3 patients with acute rejection following heparin therapy. These data indicate that 99mTc sulfur colloid is superior to 67Ga citrate in establishing the diagnosis of transplant rejection and also provides more timely information.

Further Evaluation of 99mTc Sulfur Colloid Accumulation in Rejecting Renal Transplants in Man and a Canine Model1

Renal transplant accumulation of 99m-Tc sulfur colloid was evaluated in 41 patients. Ninety-five examinations were performed comparing transplant with bone marrow activity and clinical or pathological diagnosis. 99m-Tc sulfur colloid accumulated in acute or chronic rejection as long as the vascular supply of the grafted kidney was not severely impaired. Accumulation was marked in chronic rejection, slight in acute rejection and absent in normally functioning transplants or in those with acute tubular necrosis. In the 10 dog models, no accumulation was seen in autografted transplants and early accumulation was demonstrated within the hyperacutely rejecting kidneys of allografted dogs.

Diagnosis of coronary artery disease with 201Tl. Computer analysis of myocardial perfusion images.

The diagnostic sensitivity of visually interpreted and computer-analyzed 201Tl myocardial perfusion images was compared to that of exercise electrocardiograms in 8 angiographically normal subjects and 24 patients with significant coronary artery disease. Visual interpretation was not significantly better than exercise ECGs. An index of perfusion homogeneity, derived from computer analysis of the 201Tl images, was more sensitive than visual interpretation (79% vs. 58%) and much more sensitive (p less than 0.05) than the exercise ECG (79% VS. 46%). The best overall sensitivity (88%) and specificity (75%) were achieved by combining computer analysis with exercise electrocardiography. The computer also permits enhanced detection of subtle perfusion changes which may not seem significant to the eye.

Renal Accumulation of 99mTc Sulfur Colloid in Transplant Rejection

Scintiphotographic visualization of renal transplant accumulation of 99mTc sulfur colloid was evaluated in 21 patients with renal transplants. Forty-one examinations were performed comparing transplant activity with bone-marrow activity and clinical or pathological diagnosis. A marked degree of transplant radiocolloid accumulation was seen in chronic rejection. Patients with normal transplant function, acute rejection, or acute tubular necrosis presented with slight or absent transplant radioactivity.

Erythropoiesis and Hyperoxia

Summary Exposure to a 50% oxygen environment produced a decrease in erythropoiesis which was paralleled by a decrease in plasma erythropoietic stimulating activity. Similar results were obtained following exposure to a 100% oxygen environment. Marrow depression produced by hyperoxia could be reversed by erythropoietic stimulants. The suppression of erythropoiesis in both partners of parabiots maintained so that one breathed 20% and the other 90-95% oxygen suggests that a humoral inhibitor is produced in the hyperoxic animal and supports the hypothesis that erythropoiesis is regulated by the dynamic interaction of erythropoietin and an erythropoietic inhibitor.