Paul V. Harper

Bone-Seeking Radionuclides: An In Vivo Study of Factors Affecting Skeletal Uptake

The factors governing the skeletal uptake of bone-seeking radionuclides in vivo have not been clearly defined. In this study, the effects of alteration in blood flow (thermal-induced) and alteration in osteogenesis (ricket-induced) on the skeletal uptake of these agents in rats were investigated. In vivo quantitative data were corroborated by the use of autoradiographic and well-counting techniques. Results indicate that the short-term uptake of commonly used bone-scanning agents is closely correlated with blood flow and is largely independent of the rate of osteogenesis.

TECHNETIUM 99M AS A SCANNING AGENT.

INTEREST has increased over the past few years in the use of technetium 99m as a radioactive tracer material for organ and tumor localization studies (1). Initially, attention was focused on this nuclide because of its favorable physical properties for biological applications (2). Subsequent chemical and physiological studies have revealed remarkably versatile characteristics which may make Tc99m the radioisotope of choice in a variety of clinical applications (3–13). This report summarizes the progress made in our laboratory during the past four years in investigating this isotope. Chemically technetium belongs in group VII-A along with manganese and rhenium, the resemblance to the latter being particularly close. The physiologic behavior of technetium compounds has not been extensively studied except for the pertechnetate. This rather stable ion resembles iodide very closely in its initial distribution in the body (14). Like iodide it is selectively concentrated in the thyroid, salivary glands, and stom...

131I‐labeled antibodies to human fibrinogen. Diagnostic studies and therapeutic trials

Homologous 131I fibrinogen and its purified antibody will concentrate in a major portion of the neoplasms of the dogs and humans into which they are injected, according to new data. This report gives the scintillation scanning results obtained after iv administration of 131I‐labeled and purified antihuman fibrinogen to 172 consecutive patients with various types of neoplasms. In 75% (129/172) of the cases the tumor, in various sites, was unequivocally located. These included mammary carcinomas (12/17), malignant melanoma (16/26), bronchogenic carcinoma (27/34), osteogenic sarcomas (9/9), hypernephromas (6/6), and primary tumors of the brain (10/18). The 131I deposition in tumor relative to normal tissue and blood was so great that in 12 terminal patients therapeutic trials were initiated using 100 to 160 me of the labeled antibody preparation. In some of these attempts, there was substantial remission of clinical symptoms. The usefulness of this technique for specific radiation therapy of tumors will be greatly improved when methods are developed for increasing 131I concentration in the peoplasm. Several approaches, including fever, endotoxin, pretreatment with fibrinolytic agents and post‐treatment with antifibrinolytic agents, are under intensive investigation in experiments and offer great promise.

Glucagon-induced hypocalcemia.

Abstract The intravenous infusion of 2 mg. of glucagon to rabbits over a period of 8 hours produced a marked fall in serum calcium, whereas the infusion of normal saline or 20 per cent dextrose failed to reproduce this effect. Glucagon is also known to lower serum phosphate and to enhance the urinary excretion of calcium and phosphate. The finding of similar serum and electrolyte changes in experimental pancreatitis forms the basis for the hypothesis that an overproduction of glucagon by an inflammed pancreas may be in part responsible for the hypocalcemia of acute pancreatitis. This hypothesis is further supported by the finding of elevated serum glucagon in clinical and experimental pancreatitis. It appears unlikely that the release of insulin, which glucagon induces, is responsible for the fall in serum calcium.

The Use of 67Ga Scanning in the Staging of Hodgkin's Disease1

Gallium-67 whole body scanning has been used to determine the extent of Hodgkins disease in 20 patients. Disease sites have been confirmed by pathological examination of tissue obtained at laparotomy or local excision biopsy, as well as chest radiographs and physical examination of superficial lymph node groups. Of 29 disease sites, 23 (79%) were correctly identified by 67Ga scanning. Six areas were thought to be involved by disease on the basis of the scan but were found to be uninvolved at surgery. Gallium-67 scanning is recommended as a useful supplement in the staging of Hodgkins disease.

The use of 67 Ga scanning in the staging of Hodgkin's disease.

Gallium-67 whole body scanning has been used to determine the extent of Hodgkins disease in 20 patients. Disease sites have been confirmed by pathological examination of tissue obtained at laparotomy or local excision biopsy, as well as chest radiographs and physical examination of superficial lymph node groups. Of 29 disease sites, 23 (79%) were correctly identified by 67Ga scanning. Six areas were thought to be involved by disease on the basis of the scan but were found to be uninvolved at surgery. Gallium-67 scanning is recommended as a useful supplement in the staging of Hodgkins disease.

Clinical myocardial imaging with nitrogen-13 ammonia

Myocardial infarcts may be clearly imaged using intravenous nitrogen-13 as carrier-free ammonia in doses of 10–30 mCi. This positron emitter is well imaged with the Nuclear Chicago HP Anger Camera with heavy collimation. The rapid blood disappearance of the agent gives good image contrast, and the short half-life and high isotope dosage give high-count density images with little radiation absorbed dose (5 mrad∕mCi total body).

Bromine-80m-labeled estrogens: Auger electron-emitting, estrogen receptor-directed ligands with potential for therapy of estrogen receptor-positive cancers

To assess their possible use for estrogen receptor (ER)-directed radiotherapy of estrogen receptor-containing cancers, two estrogens were synthesized with the Auger electron-emitting nuclide bromine-80m and administered to immature female rats. Both the triphenylethylene-based estrogen, [80mBr]-2-bromo-1,1-bis(4-hydroxyphenyl)phenylethylene (Br-BHPE) and the steroidal estrogen [80mBr]17 alpha-bromovinylestradiol, showed substantial diethylstilbestrol-inhibitable localization only in the estrogen target tissues, the uterus, pituitary, ovaries, and vagina and, except for the liver and intestines, generally lower concentrations in all other tissues at both 0.5 and 2 h. The [80mBr]Br-BHPE (specific activity, 8700 Ci/mmol), was shown to bind specifically to the low salt extractable ER of the rat uterus. Comparing i.p., i.v., and s.c. administration of [80mBr]BHPE the i.p. route was found to be particularly advantageous to effect maximum, DES-inhibitable concentrations of radiobromine in the ER-rich target organs in the peritoneal cavity. When the tissue distribution of the [80mBr]Br-BHPE was compared with that of sodium bromide-80m, it was apparent that no substantial amounts of radiobromine were released from the bromoestrogen prior to its target tissue localization. The substantial concentration of these bromine-80m-labeled estrogens in ER-rich tissues, combined with previously reported evidence for the effective radiotoxicity of Auger electron-emitting nuclides within cell nuclei suggest a good potential for such ligands for therapy of ER positive cancers.

Biventricular dynamics during quantitated anteroseptal infarction in the porcine heart.

The porcine heart has been shown to have close anatomic similarity to the human heart and was used as the experimental model in this study to gain further understanding of the early responses of both ventricles during acute anteroseptal myocardial infarction. High fidelity pressure and flow data were measured and multiple preejection and ejection variables were calculated for both ventricles. Infarct weight and distribution in both ventricles were quantitated. The standard infarction resulted from single stage ligation of the left anterior descending coronary artery just beyond its midpoint and second left ventricular branch. It comprised an average of 15.8 percent of total ventricular myocardium with an infarct/perfused ratio of 0.62 and a periinfarction transition zone of 7.5 mm, and involved significant portions of both ventricles and the interventricular septum. Performance characteristics of both ventricles were altered significantly by anteroseptal infarction and involved all phases of contraction--end-diastole, isovolumic systole and ventricular ejection. Although contractile alterations in the right ventricle were significant, they were somewhat delayed, yielding relatively low correlation coefficients with analogous left ventricular contractile indexes. These correlations became quite distinct during specific ventricular stresses. Comparison of anterolateral and anteroseptal infarction, matched in terms of infarct size, indicated that the right ventricular changes in the latter were related to direct involvement of the right ventricular free wall and septum rather than secondary to left ventricular alterations.

Positron Emission Tomography for the Evaluation of Pancreatic Disease

Efficient techniques for native-labeling of amino acids have been combined successfully with emission tomography to yield significant improvements in pancreatic imaging. Carbon-11-labeled tryptophan appears to be the best agent available currently for imaging the pancreas. Optimum scanning times begin 30 min after tracer administration. Positron emission tomography with 11C-tryptophan is capable of defining both morphological and functional alterations in the pancreas. Tumors as small as 2 cm in diameter can be detected, but reliable differentiation of pancreatic cancer from pancreatis may not be possible even with this improved imaging technique. Longitudinal multiplane emission tomography in single-photon mode with the Pho/Con provides an efficient and satisfactory approach to pancreatic imaging with the positron-emitting radiopharmaceuticals.