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Biomedical subjects

F F Knapp

Publications and source records attributed to F F Knapp.

At least 145 records · Page 8Linked to original sources
PubMed1982

Synthesis and biological evaluation of 17-[131I]iodo-9-telluraheptadecanoic acid, a potential imaging agent.

A method has been developed for the preparation of terminal halogenated tellurium fatty acids (X-R-Te-R'-COOH). The synthesis and physical properties of 17-bromo- and 17-iodo-9-telluraheptadecanoic acid (17-iodo-9-THDA) are described. The radiohalogenated agents are of interest as a result of their expected pronounced and prolonged heart uptake and potential use for evaluation of regional myocardial fatty acid metabolism. Evaluation in rats indicates that the myocardial uptake of 17-[131I]iodo-9-telluraheptadecanoic acid (17-[131I]iodo-9-THDA) is accompanied by significant in vivo deiodination. A comparison of the heart uptake and deiodination of 17-[131I]iodo-9-THDA and 16-[131I]iodopalmitic acid has demonstrated a close similarity in blood levels of radioactivity and thyroid uptake of radioiodide after administration of these agents to rats. These data suggest that the mechanism of deiodination of terminal radioiodinated alkanoic acids primarily results from direct cleavage of the carbon-iodine bond and not from loss of radioiodine from the final catabolite.

Animals↗
PubMed1982

A new, well-retained myocardial imaging agent: radioiodinated 15-(p-lodophenyl)-6-tellurapentadecanoic acid.

A method involving the acid-catalyzed decomposition of a piperidyltriazene intermediate in the presence of radioiodide has been developed for the synthesis of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid. The iodine-125-labeled agent shows rapid, pronounced myocardial uptake in rats (5.30-6.45% injected dose/g after 5 min) and also exhibits the prolonged retention previously observed with 9-[123mTe]telluraheptadecanoic acid (9-123mTe]HDA). After 6 hr, the heart uptake remained high (3.89-5.33%) dose/g) and decreased only to 3.02-3.41% dose/g after 24 hr. Very low blood activity was detected (0.24-0.27% dose/g at 5 min; 0.29-0.32% dose/g at 6 hr) and the heart-to-blood ratios were high (22:1 at 5 min; 15:1 at 6 hr). Minimal deiodination was demonstrated by the low thyroid uptake (1.41-1.63% dose/g at 5 min; 5.33-7.08% dose/g at 6 hr). The rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination make this agent attractive for further evaluation.

Animals↗
PubMed1981

Potential pancreatic imaging agents. Tellurium-123m labeled DL-alpha-amino-gamma-(phenyltelluro)butyric acid.

This report describes the first successful preparation of a 123mTe-labeled alpha-amino acid as a potential pancreatic imaging agent. Tellurium-123m labeled DL-alpha-amino-gamma-(phenyltelluro)butyric acid was prepared by basic hydrolysis of the radiolabeled 5-[beta-(phenyltelluro)ethyl]hydantoin. The hydantoin was prepared by the reacitron of 123mTe-labeled phenyltellurol, generated by sodium borohydride reduction of diphenyl ditelluride, with 5-(beta-bromoethyl)hydantoin. Tissue distribution studies in rats with the 123mTe-labeled amino acid for periods varying from 30 min to 24 h demonstrated only marginal pancreatic accumulation of radioactivity. The significant result of these studies is that a general synthetic method has been developed for the preparation of 123mTe-labeled amino acids.

Aminobutyrates↗
PubMed1981

Effects of chain length and tellurium position on the myocardial uptake of Te-123m fatty acids.

A series of Te-123m-labeled fatty acids has been synthesized and studied in rats. In the series of compounds studied, the position of the Te-123m heteroatom was not as important as the total chain length, which dramatically affected the heart uptake. Five minutes after injection, significant heart uptake (1.7-2.3% of injected dose) was observed for agents with C15, C17, and C21 chain lengths, in which Te-123m replaced a methylene group in either the 6, 9, 11, or 17 positions, and the heart-to-blood ratios were high. An important observation was the prolonged retention of radioactivity for at least one hour after injection. In contrast, agents with shorter C13 chain lengths, with Te-123m in either the 6 or the 9 position, exhibited only low heart uptake (0.1-0.3% of injected dose).

Animals↗
PubMed1981

Myocardial imaging with 9-[Te-123m]telluraheptadecanoic acid.

The distribution of radioactivity in the myocardium of rats and dogs infarcted by ligation of the left anterior coronary artery has been determined after intravenous injection of 9-[Te-123m]telluraheptadecanoic acid (Te-123m HDA]. In rats the normal myocardium concentrated radioactivity (3.7% +/- 0.28 injected dose/g) to nearly three times that in the zones of infarction (1.12% +/- 0.18 dose/g0. The focal defects detected in the gamma-camera images of rats and dogs correspond well with areas of infarction identified in the excised hearts by staining with triphenyltetrazolium chloride. The distribution of radioactivity from Te- 123m HDA in dog hearts sectioned at autopsy showed a linear correlation (r = 0.94) with blood flow as determined with scandium-46-labeled microspheres.

Animals↗
PubMed1980

Tellurium- 123m-labeled 23-(isopropyl telluro)-24-nor-5 alpha-cholan-3 beta-ol: a new potential adrenal imaging agent.

Tellurium-123m-labeled 23-(isopropyl telluro)-24-nor-5 alpha-cholan-3 beta-ol (24-telluracholestanol, or 23-ITC) has been prepared as a potential adrenal-imaging agent. The new agent was synthesized by the coupling of 3 beta-acetoxy-23-bromo-24-nor-5 alpha-cholan with Te-123m-labeled sodium isopropyl tellurol. Tissue distribution experiments in both male and female rats indicate a high adrenal concentration of a radioactivity following administration of this agent. In female rats the adrenal glands accumulated 4.5% of the injected radioactivity only 1 day after administration of Te-123m-23-ITC. The adrenal-to-liver ratio was 42 after 1 day, and this increased to 100 after 3 days. Chromatographic analyses of lipid extracts from adrenal, ovary, liver, and lungs suggest that this agent is metabolized by these tissues. Examination of the rats' excretory products has indicated that approximately 50% of the administered radioactivity is excreted in the feces within 5 days after injection of Te-123m-23-ITC. Moreover, the adrenals and ovaries of rats have been clearly imaged with this agent, both with a rectilinear scanner and with an RC type of proportional-counter camera.

Adrenal Glands↗
PubMed1980

The effect of structural modifications on the adrenal uptake of steroids labeled in the side chain with tellurium-123m.

A series of structurally modified steroids labeled in the side chain with Te-123m have been prepared and tested in rats to determine the critical structural features required for maximal adrenal uptake of this new class of potential adrenal-imaging agents. The Te-123m steroids investigated contained structural modifications of both the nucleus and side chain. Tissue distribution experiments and rectilinear scans indicated that 23-(isopropyl telluro)-24-nor-5 alpha-cholan-3 beta-ol (saturated nucleus), and 24-(isopropyl telluro)-chol-5-en-3 beta-ol (nuclear double bond) showed pronounced adrenal uptake after 1 day, with adrenal-to-liver ratios of 41 and 27, respectively. These results indicate that a combination of structural features is required for significant adrenal uptake of steroids labeled in the side chain with Te-123m. The structural requirements include a trans ring structure, an equatorial C-3 hydroxyl group, and a 17 beta side chain of moderate length.

Adrenal Glands↗
PubMed1980

Radiation dosimetry of two new tellurium- 123m-labeled adrenal-imaging agents: concise communication.

The absorbed radiation doses to humans from 23-(isopropyl[123mTe]telluro)-24-nor-5 alpha-cholan-3 beta-ol (Te-123m-23-ITC) and 24-(isopropyl[123mTe]telluro)-chol-5-en-3 beta-ol(Te-123m-24-ITC) have been calculated, based on rat biological data, to assess the relative radiation risks to humans from these two new adrenal-imaging agents. The estimated radiation doses to several critical organs have been compared with dose estimates for a variety of other radiolabeled steroids that have been designed as adrenal-imaging agents. Dose estimates to selected organs from Te-123m-23-ITC are as follows (rad/mCi): adrenals 98; ovaries 8.0; liver 1.6. Similar estimated values for Te-123m-24-ITC are: adrenals 210; ovaries 13; liver 2.0. The radiation dose estimates for these two agents are comparable to the calculated radiation doses from 6 beta-[(methyl[75Se]seleno)methyl]-19-nor-cholest-5(10)-en-3 beta-ol (Scintidren) and 19-[131I]iodocholest-5-en-3 beta-ol (NP-59), two agents currently in clinical use for the diagnosis of adrenal disease.

Adrenal Glands↗
PubMed1978

Sterol synthesis. Chemical synthesis, structure determination and metabolism of 14 alpha-methyl-5 alpha-cholest-7-en-3 beta, 15 beta-diol and 14 alpha-methyl-5 alpha-cholest-7-en-3 beta, 15 alpha-diol.

14alpha-Methyl-5alpha-cholest-7-en-3beta,15beta-diol and 14alpha-methyl-5alpha-cholest-7-en-3beta,15alpha-diol have been prepared by chemical synthesis. Unequivocal establishment of these structures was based upon X-ray crystallographic analysis of 3beta-p-bromobenzoyloxy-14alpha-methyl-5alpha-cholest-7-en-15beta-ol and was supported by other spectroscopic data. Spectroscopic data were presented for the following compounds prepared in this study: 3beta-benzoyloxy-5alpha-cholest-8(14)-en-15-one, 3beta-benzoyloxy-14alpha-methyl-5alpha-cholest-7-en-15-one, 3beta-benzoyloxy-14alpha-methyl-5alpha-cholest-7-en-15beta-ol, 14alpha-methyl-5alpha-cholest-7-en-3beta, 15beta-diol, 14alpha-methyl-5alpha-cholest-7-en-3beta, 15alpha-cholest-7-en-15beta-diol, 14alpha-methyl-5alpha-cholest-7-en-3beta, 15alpha-diol, 3beta, 15alpha-bis-benzoyloxy-14alpha-methyl-5alpha-cholest-7-ene, 3beta-p-bromobenzoyloxy-14alpha-methyl-5alpha-cholest-7-en-15beta-ol and 3beta, 15beta-bis-p-bromobenzoyloxy-14alpha-methyl-5alpha-cholest-7-ene. Studies of the metabolism of [16-3H]-14alpha-methyl-5alpha-cholest-7-en-3beta, 15beta-diol and [16-3H]-14 alpha-methyl-5 alpha-cholest-7-en-3beta, 15alpha-diol in liver homogenates of female rats indicated that only the 3beta, 15beta-diol was convertible to cholesterol.

Animals↗
PubMed1976

Mass spectral fragmentation of 5alpha-hydroxysteroids.

The mass spectra of a number of C-4alpha- and C-4beta-alkylated cholestan-3beta, 5alpha-diols have been found to contain an intense ion at m/e 332. the corresponding 6beta-alkylated (R) cholestan-3beta, 5alpha-diols exhibit an abundant ion at m/e 331 + R. The mass spectra of cholestan-5alpha-ol and cholestan-3beta, 5alpha-diol also show an ion at m/e 332 which, however, is of relatively low abundance. The ion in question appears to arise from fragmentation processes which are characteristics of 5alpha-hydroxysteroids. A similar fragmentation has been found to occur in cases of C-4 and C-6beta-alkylated 5alpha-hysroxy-cholestan-3-ones. The results of isotopic labeling, high resolution and metastable ion defocusing studies are discussed in terms of the origin of several of the ions in the spectra of the various compounds.

Cholestanes↗
PubMed1976

Mass spectrometry of sterols. Electron ionization induced fragmentation of C-4-alkylated cholesterols.

The electron impact ionization of C-4-alkylated cholest-5-en-3beta-hydroxysterols has been investigated. The mass spectra of the C-4-alkylated cholesterols contain a number of ions in the high mass region for which analogous ions are not found in the spectrum of cholesterol. Detailed studies of the composition and origin of these ions have been made by high resolution mass spectrometry and analysis of metastable ions. In addition, a large number of isotopically (deuterium and 18O) substituted C-4-alkylated analogues have been prepared to assist in the interpretation of the spectra. The combined results indicate the occurrence of a number of very complex and unusual electron ionization induced fragmentations. Most notable of the findings reported herein concerns the demonstration of the formation of an ion involving loss of the elements of ring A with an intramolecular shift of the oxygen and hydrogen atoms of the hydroxyl function to the charge-retaining species.

Chemical Phenomena↗
PubMed1975

Chemical synthesis, spectral properties, and chromatography of 4alpha-methyl and 4beta-methyl isomers of (24R)-24-ethyl-5alpha-cholestan-3beta-ol and (24S)-24-ethyl-cholesta-5,22-dien-3beta-ol.

Described herein are chemical syntheses of the following compounds: 4-methyl-(24S)-24-ethyl-cholesta-4,22-dien-3-one, 4,4-dimethyl-(24S)-24-ethyl-cholesta-5,22-dien-3-one, 4beta-methyl-(24R)-24-ethyl-5alpha-cholestan-3beta-ol, 4alpha-methyl-(24R)-24-ethyl-5alpha-cholestan-3beta-ol, 4alpha-methyl-(24S)-24-ethyl-5alpha-cholest-22-en-3beta-ol, 4-methyl-6beta-bromo-(24S)-24-ethyl-cholesta-4,22-dien-3-one, 4alpha-methyl-(24S)-24-ethyl-cholesta-5,22-dien-3beta-ol, 4alpha,5alpha-epoxy-(24S)-24-ethyl-cholesta-4,22-dien-3beta-yl acetate, 4beta-methyl-(24S)-24-ethyl-cholest-22-en-3beta,5alpha-diol, 4beta-methyl-5alpha-hydroxy-(24S)-24-ethyl-cholest-22-en-3beta-yl acetate, 4beta-methyl-(24S)-24-ethyl-cholesta-5,22-dien-3beta-yl acetate and 4beta-methyl-(24S)-24-ethyl-cholesta-5,22-dien-3beta-ol. Chromatographic, nuclear magnetic resonance, and mass spectral data are presented for the compounds under consideration.

Cholestadienols↗