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Biomedical subjects

P V Harper

Publications and source records attributed to P V Harper.

At least 19 recordsLinked to original sources
PubMed1997

In vitro and in vivo studies on the development of the alpha-emitting radionuclide bismuth 212 for intraperitoneal use against microscopic ovarian carcinoma.

OBJECTIVE: Our objective was to develop the alpha-emitting radionuclide bismuth 212 for possible intraperitoneal use against microscopic ovarian cancer. STUDY DESIGN: The radiobiologic effectiveness of bismuth 212 was compared in vitro to x rays and chromic phosphate phosphorus 32). The distribution, toxicity, and maximum tolerated dose of bismuth 212 were determined after intraperitoneal administration in animal models. Dose estimates in animals and humans were made. RESULTS: In in vitro studies bismuth 212 was three times more effective in eradicating tumor cells grown in monolayers and in 800 microm spheroids. In in vivo studies bismuth 212 was distributed uniformly after intraperitoneal administration. The maximum tolerated dose in rabbits was 60 mCi. There was reversible hematologic toxicity with minimal organ damage. Bismuth 212 prolonged survival and cured up to 40% of animals inoculated with Ehrlich carcinoma cells. Dose estimates made from these studies indicated that dosages administered were effective in eradicating tumor cells and were within the radiotolerance of normal human tissue. CONCLUSION: Bismuth 212 appears to be a suitable candidate for intraperitoneal use against microscopic ovarian cancer.

Adenocarcinoma↗
PubMed1991

Production of no carrier added 80mBr for investigation of Auger electron toxicity.

80mBr (half-life = 4.43 h) is an Auger electron emitting nuclide with convenient properties for investigating Auger electron cytotoxicity and with potential for labeling in vivo radiotherapeutic agents. We have investigated three cyclotron target systems capable of generating 80mBr of sufficiently high specific radioactivity (no carrier added) for biomedical experiments. A 83Kr gas target irradiated with 21.5 MeV deuterons made 80mBr at a production yield of 1.6 +/- 0.2 mCi/muAh at saturation. A five-fold increase in 80mBr yield was obtained from 15 MeV proton irradiation of thin elemental Se enriched in 80Se targets although technical improvements are expected to further raise this production yield. This route is therefore superior for current medical cyclotrons. Irradiation of a reusable 80Se copper selenide target also yielded multi-millicurie amounts of 80mBr, and recovery of radiobromine by dry distillation is faster and more convenient than in the elemental Se target, but an optimum copper selenide target for 80mBr production has not yet been built.

Bromine Radioisotopes↗
PubMed1991

Increased nuclear damage by high linear energy transfer radioisotopes applicable for radiodirected therapy against radiologic malignancies.

High linear energy transfer radioisotopes carried by appropriate agents have been proposed for receptor-directed radiotherapy. Two such classes of isotopes are Auger electron and alpha-emitting nuclides. To determine the relative cytotoxicity and nuclear damage to cells produced by these two classes of nuclides, we compared bromine-80m (80mBr), an Auger-electron-emitting radionuclide with a 4.4-hour half-life, with bismuth-212 (212Bi), an alpha-emitter with a 1-hour half-life. Because of the short path length of the Auger electrons, 80mBr was radiotoxic only when incorporated into DNA, such as in the form of [80mBr]bromodeoxyuridine ([80mBr]BrUdR). Both agents induced linear increases in chromosome aberration frequency, however, [80mBr]BrUdR caused multiple aberrations including the shattering of parts of the chromosomes. While, in contrast, a 2-hour exposure of cells to 212Bi, chelated to DTPA, a form which does not enter the cell, induced much less extensive chromosome damage. Exposure to equivalent activities of Auger electrons or alpha-particles results in 5 times more damage in Auger-electron-exposed cells. However, estimates of dose suggest they are equally toxic. Unlike Auger electrons, alpha-particles did not need to be in as close proximity to the DNA to have clastogenic and radiotoxic effects.

Alpha Particles↗
PubMed1991

Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys.

We have evaluated the biodistribution of human low-density lipoprotein (LDL) radiolabeled with 99mTc or with 123I-tyramine cellobiose in rabbits and in rhesus monkeys. Biodistribution was assessed after intravenous injection of radiolabeled LDL by quantitative analysis of scintigrams, counting of excreta, and counting of tissues at necropsy. Both rabbits and monkeys showed lower renal uptake (123I:99mTc approximately 1:3, as regional percent injected activity corrected for physical decay) and excretion (1:2 to 1:4), but higher hepatic (1.5:1 to 2:1) and cardiac (1.7:1 to 4:1) uptake of 123I than of 99mTc. Adrenals were visualized in normolipemic animals with 123I-tyramine cellobiose-LDL but not with 99mTc-LDL. Hyperlipemic animals showed increased cardiac (up to six-fold) and decreased hepatic activity (by 50%-60%) of both radionuclides. We conclude that 123I-tyramine cellobiose-LDL is better suited than 99mTc-LDL for dynamic studies of LDL metabolism in vivo.

Animals↗
PubMed1990

Comparison of the distribution of bromine-77-bromovinyl steroidal and triphenylethylene estrogens in the immature rat.

The specific uptake and distribution of steroidal and non-steroidal [77Br]bromovinylestrogens were studied in immature female rats to assess the potential of these radioligands for imaging or therapy of estrogen receptor (ER) positive cancers. E-17 alpha [77Br]bromovinylestradiol, its 3 methyl ether and 11 beta-methoxy derivative, as well as the triphenylethylene estrogen, 1,1-bis[4-hydroxy-phenyl]-2-[77Br]bromo-2- phenylethylene all showed diethylstilbestrol inhibitable, specific uptake of radiobromine between 2 and 16 hr after i.p. administration. The highest concentrations in the estrogen target tissues and the highest target tissue-to-blood ratios were found with E-17 alpha-[Br]bromovinyl-11 beta-methoxyestradiol, but it also had rather high nonspecific uptake in all tissues. The triphenylethylene estrogen showed comparable specific uptake in estrogen target tissues to 17 alpha [77Br]bromovinylestradiol at 2 hr but better apparent retention, indicated by higher specific target tissue levels at the later time points. Thus, [77Br]bromovinyl-11 beta- methoxyestradiol and 1,1-bis[4-hydroxyphenyl]-2-[77Br]bromo-2-phenylethylene appear most favorable for these applications.

Animals↗
PubMed1989

Planar positron imaging of rubidium-82 for myocardial infarction: a comparison with thallium-201 and regional wall motion.

Rubidium-82 (Rb-82) is a generator-produced, short half-life (76 seconds) positron emitting potassium analog. Using a mobile gamma camera equipped with a rotating tungsten collimator and high-energy shielding, we examined the use of Rb-82 in the coronary care unit and clinical laboratory for detection of perfusion defects due to myocardial infarction. We studied 31 subjects, 10 patients with acute myocardial infarction, 12 with remote myocardial infarction, and nine controls. Rb-82 images were compared with Tl-201 and regional wall motion for detection of infarct-related arteries. Of the 22 patients with myocardial infarction, 16 were identified with Rb-82 and Tl-201. In nine control subjects, eight were normal with each method. Correlation between Rb-82 and Tl-201 defect scores was excellent. Sensitivity and specificity for infarct-related arteries were similar for Rb-82, Tl-201, and wall motion imaging. Thus planar Rb-82 imaging can detect MI reliably in the coronary care unit and in the clinical laboratory.

Coronary Care Units↗
PubMed1989

Multiparameter extrapolation of biodistribution data between species.

Values of an inaccessible biological parameter in man may be predicted from values measured in animals by correlating with a parameter accessible in both species, such as body weight, energy production, excretion rate, etc. Predicting toxic effects, from environmental chemicals, of therapeutic doses for drug administration and of radiation absorbed dose from medical and environmental radioactivity depends on the rationalization of relationships between concentration and time when scaling to humans from animal data. For example, the retention of 99mTc, injected intravenously as pertechnetate, reaches 10% in the mouse at about 1 d, but this level occurs in humans at about 7 d. Making a simultaneous transformation between two species for the concentration and time variables by using a method of least-squares fitting, we have derived a series of transformation factors for several species. When correlated with a biological parameter such as body weight, these factors can be used to yield predicted values that are in good agreement with measured values. This system may be used with any related variables, making it useful for predicting other types of biological data.

Animals↗
PubMed1988

Bromine-80m radiotoxicity and the potential for estrogen receptor-directed therapy with auger electrons.

While theoretically feasible, estrogen receptor (ER)-directed radiotherapy of hormone-dependent cancers has not been realized because no ER-seeking ligand with an appropriate radiotoxic potential has been identified. Since an appropriate nuclide is a key component we studied the 4.4-h half-life, Auger electron-emitting nuclide bromine-80m. When incorporated into DNA this nuclide was radiotoxic to cells in culture and caused substantial chromosomal damage, while similar concentrations of bromine-80m as bromide or bromoantipyrine were without effect. The mean lethal dose for bromine-80m was 45 atoms per nucleus which is consistent with use in receptor-positive cancers with limited numbers of ER.

Animals↗
PubMed1988

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.

Animals↗
PubMed1980

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.

Carbon Radioisotopes↗
PubMed1980

Accumulation of technetium-99m pyrophosphate in experimental infarctions in the rat.

Cardiac accumulation patterns of pyrophosphate labelled with techetium-99m (TcPyP) in rats one hour to 7 days after coronary artery ligation were studied by light microscopy, myocardial scintigraphy, imaging the isolated heart and by direct measurement of tissue activity. Results suggest that myocardial cells taking up TcPyP are irreversibly damaged and that the disappearance of TcPyP uptake coincides with the removal of necrotic cells by phagocytes.

Animals↗
PubMed1979

Thallium-201 imaging in assessment of aortocoronary artery bypass graft patency.

Fifteen patients with significant coronary artery disease confirmed by cardiac catheterisation were studied before and after aortocoronary artery bypass graft surgery by rest and exercise 201Tl myocardial scintigraphy in an attempt to predict graft status non-invasively. Segmental myocardial perfusion comparisons in pre- and postoperative exercise images allowed correct predictions of high (greater than or equal to 67%) or low (less than or equal to 50%) graft patency rates in 10 of 15 patients, while similar comparisons in postoperative rest and exercise images yielded 13 of 15 correct predictions. Furthermore, 20 of 21 myocardial segments with increased postoperative perfusion when compared with corresponding segments in preoperative exercise studies were supplied by patent grafts. Regional graft occlusion, however, was difficult to predict. It was also difficult to predict graft status when myocardial segments were shown to have unchanged perfusion postoperatively as compared with the preoperative segmental assessment. Despite these limitations, the non-invasive technique of 201Tl imaging can provide useful information regarding coronary artery bypass graft patency.

Adult↗
PubMed1977

Selection of chemotherapy for metastatic mammary cancer by effect on cesium-131 uptake.

Cesium-131 was administered intravenously to 39 patients with superficial metastases of mammary carcinoma and the concentration in tumor was compared with that in normal tissue by application of a detector in vivo, before and after 1 to 5 days of chemotherapy with cyclophosphamide (CP), 5-fluorouracil (FU), or diethylstilbestrol. A change of the cesium concentration ratio (tumor/normal tissue) greater than 15% after brief treatment correctly predicted the therapeutic effect after 1 to 39 months on the tumors that were tested in 30 of 33 tests. No reliable correlation could be made in the remaining 21 tests in which the change of ratio was less than 15%. The concentration of cesium-131 in the skin, fat, and skeletal muscle of mice was not appreciably altered by treatment for 5 days with CP or FU.

Antineoplastic Agents↗
PubMed1977

Nitrogen-13-labeled ammonia for myocardial imaging.

Cyclotron-produced nitrogen-13 (half-life 10 min), as labeled ammonia (13NH4+), has been evaluated as a myocardial perfusion imaging agent. The regional myocardial uptake of 13NH4+ has been shown to be proportional to regional tissue perfusion in animal studies. Intravenously administered 13NH4+ is rapidly cleared from the circulation, being extracted by the liver (15%), lungs, myocardium (2%-4%), brain, kidney, and bladder. Myocardial ammonia is metabolized mainly to glutamine via the glutamine synthetase pathway. Pulmonary uptake is substantial, but usually transient, except in smokers where clearance may be delayed. The position annihilation irradiation (511 keV) of 13N may be imaged with a scintillation camera, using either a specially designed tungsten collimator or a pinhole collimator. After early technical problems with collimation and the production method of 13NH4+ were overcome, reproducible high quality myocardial images were consistently obtained. The normal myocardial image was established to be of a homogeneous "doughnut" configuration. Imaging studies performed in patients with varying manifestations of ischemic and valvular heart disease showed a high incidence of localized perfusion defects, especially in patients with acute myocardial infarction. Sequential studies at short intervals in patients with acute infarction showed correlation between alterations in regional perfusion and the clinical course of the patient. It is concluded that myocardial imaging with 13NH4+ and a scintillation camera provides a valid and noninvasive means of assessing regional myocardial perfusion. This method is especially suitable for sequential studies of acute cardiac patients at short intervals. Coincidence imaging of the 511 keV annihilation irradiation provides a tomographic and potentially quantitative assessment of the regional myocardial uptake of 13NH4+.

Ammonia↗
PubMed1977

Assessment of diagnostic value of technetium-99m pyrophosphate myocardial scintigraphy in 80 patients with possible acute myocardial infarction.

The diagnostic value of technetium-99m-pyrophosphate (Tc-pyrophosphate) myocardial scintigraphy was determined in 80 consecutive patients who had been admitted to the coronary care unit in order to rule out an acute myocardial infarction. Scintigraphic findings obtained within 5 days of admission were correlated with the final cardiac diagnosis determined for each patient. Significant myocardial uptake of Tc-pyrophosphate (positive scans) occurred in 13 of 22 patients (59%) who had enzyme and/or electrocardiographic proven acute myocardial infarct: 3 out of 5 with transmural myocardial infarct, 9 of 16 with nontransmural myocardial infarct, and 1 patient with left bundle-branch block. Of 58 patients who showed no evidence of acute myocardial infarction, positive scans occurred in 14 of 33 patients who had unstable angina pectoris (42%), 0 of 6 who had congestive heart failure, 6 of 9 who had other acute cardiac syndromes, and in 0 of 10 who had noncardiac chest pain. In the patients with unstable angina pectoris positive scans could not be predicted on the basis of the history, electrocardiographic findings or the arteriographically determined severity of the coronary artery disease. Blood levels of Tc-99m activity measured in 21 cardiac patients and in 6 volunteers did not correlate with the uptake intensity of Tc-pyrophosphate. These findings suggest caution in the use of this imaging method for the diagnosis of acute myocardial infarct in patients admitted with 'rule out myocardial infarction'.

Acute Disease↗
PubMed1976

Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia.

The short half-life positron emitter 13N, as labeled ammonia (13NH4+), was evaluated as a myocardial imaging agent. Regional myocardial uptake of 13NH4 correlated with the distribution of labeled microspheres in experimental myocardial infarction. Using intravenous 13NH4+, myocardial scintigraphy was performed in 85 cardiac patients and 27 normal subjects. Ninety-five scintigrams were suitable for analysis. Eighteen of 24 normal subjects had homogeneous myocardial images; six had inhomogeneous images attributable to early technical problems. Perfusion defects were observed in the scintigrams of 82% (57/65) of patients with coronary artery disease, being most common in patients with myocardial infarction (27/28). Six sequential studies showed changes in perfusion consistent with the clinical course of each patient. Scintigraphic abnormalities were also observed in 4/6 patients with valvular heart disease. 13NH4+ myocardial scintigraphy is a valid and sensitive method of assessing regional myocardial perfusion and is especially useful for sequential imaging at short intervals.

Acute Disease↗