Comparison of 19-lodocholesterol and 6-lodomethylnorcholesterol as adrenal-scanning agents.

The two adrenal-specific compounds, 19-iodocholest-5-en-3beta-ol (19-iodocholesterol) and 6beta-iodometyly-19-norcholest-5(10)-en-3beta-ol (6-iodomethylnorcholesterol), synthesized pure in gram amounts have been labeled with iodine-125 and used for tissue-distribution studies in the rat. Radioactivity from 6-iodomethylnorcholesterol is accumulated in the rat adrenal gland at least 18 times more than is radioactivity from 19-iodocholesterol at 24 hr, and 50 times more at 72 hr. The use of radioactive 6-iodomethylnorcholesterol gave superior adrenal images in rats at earlier times than did radioactive 19-iodocholesterol, and the former should be equally superior when used in humans.

In vivo binding in rat brain and radiopharmaceutical preparation of radioiodinated HEAT, an alpha-1 adrenoceptor ligand.

In vivo binding of [125I]-2-[beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ([125I]HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of [125I]HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of [125I]HEAT is saturable. At 4 hr, [125I]HEAT or [123I]HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and [125I]HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity.

Biodistribution and radiation dosimetry of radioiodinated-SCH 23982, a potential dopamine D-1 receptor imaging agent.

Radioiodinated-SCH 23982 is a potential agent for the imaging of dopamine D-1 receptors in the human brain. In vivo binding of [125I]SCH 23982 to D-1 receptors in rat brain was determined over 4 hr. The ratio of activity in striatum and frontal cortex to that in cerebellum increased over the first 2 hr to maximum values of 4.4:1 and 2.1:1, respectively. The percent injected dose in whole brain at 0.5 and 2 hr were 0.62 and 0.15, respectively. Administration of the antagonists propranolol (beta-1), prazosin (alpha-1), haloperidol (D-2) and ketanserin (5HT-2) did not significantly alter the striatum/cerebellum ratio; however, SCH 23390, a D-1 antagonist, totally blocked ligand uptake by striatum and frontal cortex. Biologic distribution data in the rat were determined after injection of 3 microCi of [125I]SCH 23982. 76% of the injected dose was excreted in 48 hr via the liver and kidneys. Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads and red bone marrow were calculated for humans using the physical decay data for 123I. The critical organ was found to be the lower large intestine which received 1.1 rad/mCi of the administered dose. The total-body dose was 63 mrad/mCi. The data indicate that [123I]SCH 23982 should be a suitable agent for imaging the D-1 dopamine receptor in the human brain by single photon emission computed tomography.

Radiation dosimetry of iodine-123 HEAT, an alpha-1 receptor imaging agent.

Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [125I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [123I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [123I]HEAT administered. The total-body dose was found to be 58 mrad per mCi.

Regional analysis of D2 dopamine receptors in Parkinson's disease using SPECT and iodine-123-iodobenzamide.

UNLABELLED: The goal of this study was to examine the relationship between D2 dopamine receptor density and levodopa dosage, disease duration and dyskinesia in Parkinson's disease (PD). METHODS: Iodine-123-iodobenzamide SPECT scans were obtained from 14 PD patients and 12 age-matched controls using a three-headed camera in conjunction with MRI and a fiducial-based image registration system to define regions of interest. Basal ganglia/cerebellum counts/voxel ratios in dorsal and ventral head of caudate and anterior and posterior putamen were measured at 30, 60, 120 and 180 min postinjection. As in 11C-raclopride studies, ratios obtained at that time when they asymptomatically approach a maximum value (180 min) were accepted as the best measure of receptor density. RESULTS: Among PD patients, a trend towards an inverse correlation between regional basal ganglia/cerebellum ratios and levodopa dosage achieved significance in ventral caudate (F = 6.244, p = 0.037); similarly, an inverse correlation between these ratios and disease duration achieved significance in anterior putamen (F = 13.144, p = 0.007). Ratios were significantly lower in anterior putamen in patients with dyskinesia (t = 3.068, p = 0.042). CONCLUSION: In PD, the previously observed inverse correlation between levodopa dosage and D2-receptor density appears to be most prominent in the least dopamine-depleted region, ventral caudate. There may be a genuine effect of disease duration on receptor density in putamen and reduced receptor density in anterior putamen may be associated with dyskinesia.

Excretion of octopamine metabolites in neuroblastoma.

The urinary concentrations of o-hydroxymandelic acid, m-hydroxymandelic acid, p-hydroxymandelic acid, homovanillic acid and vanillylmandelic acid were determined in 57 healthy children and 9 patients with neuroblastoma. The concentrations of o-hydroxymandelic acid and p-hydroxymandelic were not significantly different for both groups whereas the concentrations of m-hydroxymandelic acid, homovanillic acid and vanillylmandelic acid were elevated 20- to 30-fold in the neuroblastoma patients.

Normal excretion of m-hydroxymandelic acid in hypertensive patients.

o-Hydroxymandelic acid (OHMA), m-hydroxymandelic acid (MHMA) and p-hydroxymandelic acid (PHMA) were measured in the urine of 42 normotensive and 54 hypertensive patients. Patients having high urinary MHMA levels were all found to be ingesting medications containing m-synephrine (phenylephrine). These patients also had high levels of urinary m-synephrine which was excreted as the glucuronide. When patients ingesting m-synephrine were excluded from the analysis, no significant differences were observed between the two groups for the urinary excretion of OHMA, MHMA and PHMA.

Chemical and radiochemical stability of the adrenal-scanning agents, 6beta-iodomethyl-19-norcholest-5(10-en-3beta-ol and 19-iodocholest-5-en-3beta-ol.

The chemical stabilities of the adrenal-scanning agents, 6beta-iodo-methyl-19-norcholest-5(10)-en-3beta-ol (6-iodomethylnorcholesterol) and 19-iodocholest-5-en-3beta-ol (19-iodocholesterol), and several of their derivatives were examined by 13C nuclear magnetic resonance. Neat 6-iodomethylnorcholesterol, sealed in glass under nitrogen and stored at 0 degrees C, remains 98 mole% chemically pure for 3 months. Neat 19-iodocholesterol, stored in the dark at 25 degrees C, remains 98 mole% chemically pure for 3 months. Either 6-iodomethylnorcholesterol-125I or-131I, informulation and stored at 5 degrees C, will remain greater than 97% radiochemically pure for at least 15 days. Labelled 19-iodocholesterol, formulated and stored under the same conditions, shows 20% decomposition after 3 weeks and 40% after 6 weeks.

Synthesis and purification of radioactive 6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol.

A method for the synthesis and purification of 6beta-iodomethyl-19-norcholest-5(10)-ene-3beta-ol-131I of greater than 98 mole% chemical purity and greater than 99% radiochemical purity is presented. Carbon-13 and proton NMR were used to establish the identity and purity. Discrepancies in the characterization of this compound, previously published by two other research groups, are discussed.

Increased urinary excretion of m-octopamine in neuroblastoma.

The urine of three patients with neuroblastoma was found to have a 3 to 5-fold elevation of m-octopamine concentration. The concentration of m-synephrine was normal in two cases and slightly elevated in the third. These findings were attributed to an increased formation of m-octopamine by this tumor.

Carbonless copy paper: a review of its chemical components and health hazards.

The components of carbonless copy paper (CCP) and the chemistry involved in its manufacture are reviewed. Claims that the routine use of CCP can cause health problems ranging from skin, eye, and lung irritation to severe headaches and neurological damage are described; yet no definitive studies have been conducted that show correlation between CCP use and these symptoms. The toxicological properties of CCP components, many of them precursors to the dye-containing microcapsules or dye solvents that may be causing these problems, are discussed. Recommendations for the minimization of possible physiological reactions to CCP include reduction of usage time; use of the CCP in a well-ventilated area; storing large quantities of CCP, both new or archived, away from work area; and the practice good hand hygiene.

Increased excretion of o-hydroxymandelic acid in phenylketonuria.

o-Hydroxymandelic acid has been found in large amounts in the urine of patients with phenylketonuria by gas chromatography mass spectrometry selected ion monitoring. Using deuterated o-hydroxymandelic acid as an internal standard, five patients were found to excrete 150-340 ng mg-1 creatinine. This may be compared with the excretion of 4-16 ng mg-1 creatine by normal subjects. Neither o-octopamine nor o-synephrine were found in urine under conditions by which 1 ng mg-1 creatinine would have been detected.