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Biomedical subjects

R N Hanson

Publications and source records attributed to R N Hanson.

At least 55 records · Page 3Linked to original sources
PubMed1985

Preparation and evaluation of 3-[125I]iodo-4-aminophentermine as a brain perfusion imaging agent. Comparison with labeled phentermine derivatives.

A radioiodinated derivative of the anorexinergic drug phentermine was synthesized and evaluated as a potential brain imaging agent. Stoichiometric iodination of the intermediate 4-aminophentermine (AmP) gave a mixture of mono and diiodo products, while the radioiodination at the no-carrier-added (NCA) level gave 73% isolated yield of the 3-[125I]iodo-4-aminophentermine with less than 2% of the diiodo derivative. The tissue distribution of the radiochemical in rats showed that it was readily extracted by the brain followed by relatively slow clearance from that organ. However, a comparison with other labeled phentermine derivatives indicated that the total brain uptake, retention and selectivity of the new agent were poorer, probably as a result of the presence of the 4-amino substituent.

Animals↗
PubMed1985

Radioiodinated 1-(diethylaminopropyl)-4-phenylpiperazine: a potential brain imaging agent.

The preparation of radioiodinated 1-(diethylaminopropyl)-4-phenylpiperazine, an analog of HIPDM, and its tissue distribution in rats are described. The precursor undergoes facile electrophilic radioiodination with radionuclides of iodine at the no-carrier-added level to give isolated yields in the 69-85% range. Biodistribution studies indicate that the radiochemical is well extracted by the brain (1.68-1.79% ID) and activity is substantially retained for 4 h (greater than 67%). Brain-to-blood ratios during the 0.25-4.0 h period were 15-23:1. The brain uptake and retention as well as the high brain-to-blood ratios suggest the potential use of this agent for regional cerebral blood flow imaging.

Animals↗
PubMed1985

Synthesis and evaluation of p-iodo-phentermine (IP) as a brain perfusion imaging agent.

p-(123I and 131I)iodo alpha,alpha-dimethylphenethylamine (p-iodophentermine, IP) as the alpha-methylated analogue of iodoamphetamine has been prepared. It is hoped that this methyl substitution will increase the lipophilicity of the agent, enhance resistance to metabolism by monoamine oxidase, and will result in increased initial uptake and slower washout from the brain as compared to N-isopropyl-p-(123I)iodoamphetamine. IP was prepared by diazotization of p-aminophentermine followed by decomposition of the diazonium salt with KI. Radioiodinated IP was prepared either by the solid-phase isotopic exchange reaction or by decomposition of the piperidinotriazene derivative with a radiochemical yield of 40-60%. Biodistribution of 131I-IP in rats showed brain uptake in the range of 1.7% dose g-1 at 5, 30 and 60 min. Imaging studies with 123I-IP in dogs showed high brain extraction and slow washout of activity.

Amphetamines↗
PubMed1984

Radiohalodestannylation: synthesis of 125I-labeled 17 alpha-E-iodovinylestradiol.

17 alpha-E-Iodovinylestradiol and its iodine-125-labeled analog were prepared by halodestannylation. The synthesis of the unlabeled compound was achieved from estrone in two steps with an overall yield of 30%. The tributylstannylvinylestradiol intermediate reacted with sodium [125I]iodide (specific activity = 2200 Ci/mmol) in the presence of hydrogen peroxide and acetic acid to give the 17 alpha-E-[125I]iodovinylestradiol in 40-60% yield after isolation by reversed phase column chromatography. The radiochemical purity was greater than 98% and no other u.v. active components could be detected by HPLC. The ease of preparation and isolation of this radioligand suggests that radiohalodestannylation may be the method of choice for this and structurally similar compounds.

Estradiol↗
PubMed1984

Preparation and evaluation of 17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol as a highly selective radioligand for tissues containing estrogen receptors: concise communication.

The moxestrol analog 17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol was prepared in 95% radiochemical yield from the corresponding 17 alpha-(tributylstannyl) vinyl compound and no-carrier-added sodium [125I]iodide. The new radioligand was evaluated in immature female rats to determine the uptake in and selectivity for tissues containing estrogen receptors. At 1, 2, and 6 hr after injection, the agent demonstrates both high selectivity (uterus to blood ratio) and a high concentration in the target tissue. These values are considerably better than those previously reported for IVE2 or for the 16 alpha-radiohalogenated estradiols. The compound's biologic properties and its ease of preparation suggest that it would be a likely candidate for clinical use as an estrogen-receptor-seeking radiopharmaceutical.

Animals↗
PubMed1984

Radioiodinated ligands for the estrogen receptor: effect of 3-o-methylation on tissue distribution.

The 3-o-methyl ethers of 17 alpha-[125I]iodovinylestradiol and 17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol were prepared in 95% and 89% isolated yields, respectively, at the no-carrier-added level from the corresponding (tri-n-butystannyl)-vinyl intermediates. The new radioligands were evaluated in immature female rats to determine their uptake in, and selectivity for, estrogen-receptor-containing tissues. At 0.5-6 hr after administration, both agents showed preferential uptake and retention by the target tissue. The values for the 11 beta-methoxy derivative, however, were significantly better than those of the 11-unsubstituted compound. Compared with the parent 3-hydroxy radioligands, the [125I]VE2-3-o-Me had lower uptake and target-to-blood ratios at all time periods, but by 6 hr the [125I]VME2-3-o-Me compound showed as high an uptake in the uterus and higher uterus-to-blood ratios. This may be related to metabolic cleavage of the 3-o-methyl group generating the parent compound, which is then sequestered by the target tissue. The results suggest that iodine-123-labeled VME2-3-o-Me would be a good candidate for in vivo gamma imaging of estrogen-containing tissues.

Animals↗
PubMed1982

Radioiodinated 1-carboxamidino-4-phenylpiperazine: a potential adrenal and myocardial imaging radiopharmaceutical.

This report describes the synthesis of radioiodinated 1-carboxamidino-4-phenylpiperazine, an aralkyl-guanidine with good adrenal and myocardial selectivity. As a tertiary aniline, the benzene portion of the molecule readily undergoes direct electrophilic radioiodination under mild reaction conditions to yield a single product with high specific activity which can be rapidly purified by anion exchange. Biodistribution studies in rats show high uptake in both the heart and the adrenals. The activity in the adrenals is retained for a prolonged period, whereas that in the heart declines with a 4-5 h half-life. The high uptake and target tissue-to-blood ratios suggest the potential use of this agent for myocardial and adrenomedullary imaging.

Adrenal Medulla↗
PubMed1982

Biodistribution of 59Fe-thiosemicarbazones.

The 59Fe-iron(II) chelates of 2-formylpyridine thiosemicarbazone (I), 5-dimethylamino-2-formylpyridine thiosemicarbazone (II), and 5-hydroxy-2-formylpyridine thiosemicarbazone (III) were prepared and their biodistribution determined in normal rats. Early accumulation of these complexes occurred in the liver, muscle and pelt with lesser amounts in the blood, kidneys and other organs. The tissue levels decreased with a 1 to 2-h half-life with the exception of the liver and intestines. The liver level tended to remain constant over the 2-h period. Accumulation in the gut resulting from hepatobiliary excretion increased over the first 60 min and then leveled off. In rats bearing a subcutaneous glioblastoma the uptake of compound I increased during the first 24 h after administration, and tumor to normal tissue ratios of 2 to 3.3 were obtained.

Animals↗
PubMed1982

E-17 alpha[125I]iodovinylestradiol: an estrogen-receptor-seeking radiopharmaceutical.

Through the use of radioiododestannylation, the specifically labeled E-17 alpha-[125I]iodovinylestradiol [(I-125)VE2] was synthesized rapidly and in high yield from the stable precursor E-17 alpha-tributylstannylvinylestradiol (SnVE2), and its biodistribution was determined in immature female rats. The agent accumulated in the uterus, achieving a peak uptake of 0.465% ID-kg/g at 2 hr. Uterus-to-blood ratios of 19 and 16 occurred at 1 and 2 hr, respectively, declining to 7 by 4 hr after injection. The uptake of (I-125)VE2 by the uterus at 2 hr was reduced 58--65% by pretreatment of the immature rats with estradiol (5 micrograms) or tamoxifen (100 micrograms), and compared with 16 alpha-[125I]iodoestradiol, (I-125)VE2 showed greater uterine uptake and similar uterus-to-blood ratios. The ease of preparation of the radioligand represents an advantage over the synthetic procedures for other estrogen-receptor-seeking agents.

Animals↗
PubMed1981

Selenium-sulfur analogs III: synthesis and biodistribution of two 75Se-labeled 4-substituted-1,2,3-selenadiazoles.

The 75Se-labeled 4-substituted-1,2,3-selenadiazole analogs of two drugs that inhibit the adrenocorticosteroid 11 beta- and 17 alpha-hydroxylase enzymes were prepared by the [75Se]selenious acid oxidation of the appropriate methyl ketone semicarbazones. The concentration of the radiolabeled compounds in the adrenal glands of rats over a 0.25--24-hr period was determined and compared with that in the blood, liver, and kidneys. The concentration in the adrenal glands and the target to nontarget ratios were much lower than those reported for other adrenocorticosteroid inhibitors. Therefore, these 1,2,3-selenadiazole agents do not have potential as adrenocorticosteroid imaging agents.

Adrenal Cortex↗
PubMed1981

Iodinated starch particles: new contrast material for computed tomography of the liver.

An iodinated starch suspension was used as a model particulate hepatic contrast agent for computed tomography (CT). The material, synthesized from starch and triiodobenzoic acid, formed a stable concentrated suspension, containing particles smaller than 4 micrometer. Following intravenous administration of 0.16 gI/kg to rabbits, approximately 85% of the injected dose was present in the liver, resulting in a 180 to 200 Hounsfield unit (1,000 scale) increase in liver CT value. The material produced marked and sustained normal liver opacification but no hepatic tumor enhancement. Lesions as small as 2 mm in diameter were detected. The approximate LD50 of the suspension in mice was 0.9 g I/kg. There were no signs of toxicity at sublethal doses. This suspension produces greater, more sustained, and more selective liver opacification than conventional biliary and urographic contrast materials.

Animals↗
PubMed1980

[125I]iodobenzoyl derivatives of acebutolol as potential myocardial imaging agents.

Three new iodobenzoyl derivatives of acebutolol, a cardioselective beta antagonist, were synthesized and labeled with iodine-125. The biodistributions of these labeled compounds were determined in normal rats and compared with that of thallium-201. Fifteen minutes following i.v. administration, the iodine-125-labeled meta- and para-iodobenzoyl acebutolols possessed the greatest ventricular uptake and the highest ventricle-to-blood and ventricle-to-lung ratios of the new agents. The corresonding values for thallium-201 were 2.5 to 3.0 times as high. The data in this study suggest that more lipophilic derivatives of the cardioselective beta antagonists will possess increased uptake and cardioselectivity, and thereby will compare more favorably with thallium-201 as myocardial imaging agents.

Acebutolol↗
PubMed1978

Selenium-sulfur analogues. 1. Synthesis and biochemical evaluation of selenotetramisole.

(+/-)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]selenazole (1-selenotetramisole) was prepared from 2-aminoselenazoline in a three-step synthetic sequence. Resolution with d-10-camphorsulfonic acid yielded the optical isomers which were compared with (+)- and (-)-tetramisole as inhibitors of alkaline phosphatase isoenzymes. At 8.7 X 10(-5) M the (-) isomer of both tetramisole and 1-selenotetramisole produced significant inhibition of bovine liver and placental isoenzymes but not of calf intestinal or human placental isoenzymes. The (+) isomers demonstrated no inhibition at these concentrations. The similarity in inhibitory activity of the (-) isomers indicates the virtual interchangeability of selenium for sulfur in the thiazolidine ring of the parent drug and the likelihood that 75Se-radiolabeled selenotetramisole can provide an in vivo tracer to tetramisole biodistribution.

Alkaline Phosphatase↗