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M Diksic

Publications and source records attributed to M Diksic.

144 records · Page 8Linked to original sources
PubMed1984

A new, simple, high-yield synthesis of "no-carrier-added" 11C-labelled DMO.

This paper describes a fast (20 min), convenient, and high yield synthesis of "no-carrier-added" 11C-labelled 5,5-dimethyloxazoladine-2,4-dione (DMO). During the synthesis [11C]phosgene is reacted in situ with 2-hydroxy-2-methylpropionamide in the presence of KOH for 20 min in a -5 degrees C bath and then for 5 min at room temperature. Filtration through a reverse-phase (C18) Sep-Pack column purifies the final product. This synthesis yields about 40 mCi of 11C-labelled DMO (radiochemical yield 40-60%) with a chemical purity exceeding 98% and a radiochemical purity exceeding 99%. The specific activity at the end of the synthesis is 80 Ci/mmol.

Carbon Radioisotopes↗
PubMed1984

A method for measurement of arterial concentration of cerebral blood flow tracer for autoradiographic experiments.

A new method for continuous monitoring of the concentration of 131I-labelled iodoantipyrine during an autoradiographic local cerebral blood flow (LCBF) experiment is described. During infusion of iodoantipyrine, radioactivity in an external femoral arteriovenous loop is monitored by a scintillation detector. Data is collected with a variable time base, and the arterial activity curve displayed visually in its entirety. The main advantage of this method is that there is no blood loss. It will therefore be of particular importance in dual-label autoradiography. This method can also be used for other gamma-emitting blood flow tracers, e.g. 123I-iodoantipyrine.

Animals↗
PubMed1984

Synthesis, receptor binding, and target-tissue uptake of carbon-11 labeled carbamate derivatives of estradiol and hexestrol.

The reaction of ethyl chloroformate with amino compounds has been evaluated as a simple route to carbon-11 labeling of steroid hormone-receptor-based imaging agents. Both a 17 beta-amino analogue of estradiol and an aminoethyl derivative of the nonsteroidal estrogen hexestrol with potential affinity for the estrogen receptor were studied. The unlabeled carbamate derivatives of the amino estrogens were prepared by standard methods, and the 11C-labeled analogues were synthesized from [11C]ethyl chloroformate, generated by purging ethanol with [11C]phosgene. Both carbamates showed weak in vitro binding affinity for the estrogen receptor, and only the 11C-labeled hexestrol exhibited a small but significant estrogen-responsive uterus uptake in immature rats.

Animals↗
PubMed1984

Evaluation of [18F]-4-fluoroantipyrine as a new blood flow tracer for multiradionuclide autoradiography.

This article reports the evaluation of [18F]-4- fluoroantipyrine (FAP) as a quantitative blood flow tracer by comparing blood flow measured with [18F]FAP to that determined simultaneously with [14C]-4-iodoantipyrine (IAP), a standard blood flow tracer, by means of double-tracer autoradiography. The single-pass extraction value (m), which indicates diffusibility of a tracer, was determined according to the procedure described by Crone . The diffusibility of FAP was essentially the same as that of IAP. The brain-blood partition coefficient for FAP was found to be similar to that for IAP, 0.89 +/- 0.01. Values of local cerebral blood flow obtained with FAP agree with those determined with IAP. From these results, we concluded that FAP is indeed as good a blood flow tracer as IAP. Since 18F is a positron-emitting radionuclide, it might be a useful tracer for blood flow measurement by positron emission tomography.

Animals↗
PubMed1984

Influence of the input function on the calculation of the local cerebral metabolic rate for glucose in the deoxyglucose method.

We describe here a modification of Sokoloff's deoxyglucose method which requires fewer blood samples but does not diminish accuracy. To calculate the local cerebral metabolism for glucose (LCMRglu), the input function containing the initial peak must be known. This requires many blood samples for accurate definition. To estimate the influence of the peak on the LCMRglu, a dummy input function was generated by extrapolating the data points after 2 min back to 0 min. Next, a biexponential curve, fitted to a reduced number of samples, was applied for the input function. The error introduced into the LCMRglu by using these different approximations was analyzed with an error function derived from an operational equation. The results indicate that the error of LCMRglu caused by neglecting the peak is less than 3%. Furthermore, the error of LCMRglu resulting from use of the biexponential approximation is a function of LCMRglu: the error decreases as the LCMRglu increases and remains at less than 3% even when only seven data points are used (half the usual number of the standard method). Finally, the LCMRglu was calculated by the biexponential curve-fitting, using the experimental data, and compared with that calculated by Sokoloff's computer program. Both methods were in good agreement. This modified method offers great advantage for simultaneous measurement of CMRglu, CBF, and other physiological parameters by means of the multiple tracer autoradiographic technique in the small laboratory animal.

Animals↗
PubMed1984

An improved approach for measurement of regional cerebral rate constants in the deoxyglucose method with positron emission tomography.

A new experimental approach was designed to measure regional rate constants for [18F]2-fluoro-2-D-deoxyglucose in the three-compartment model. A programmed infusion was used to keep the plasma tracer concentration constant for the first 20 min. Positron emission tomography images of the brain were taken every minute for 20 min in a low-resolution mode, then every 15-20 min for 2-3 h in a medium-resolution mode. Two simplified operational equations for the calculation of the regional rate constants were derived that incorporated the contribution of the vascular compartment to tissue activity. The first equation was applied to data collected during the initial 20 min (when the concentration of plasma tracer was constant) to estimate the values of k1*, k2*, k3*, and the fraction of the vascular compartment. The second equation was applied to data collected during the whole experimental period to find the value of k4* and to provide a better estimate of k3*. The regional rate constants measured experimentally in three dogs and a brain tumor patient agreed well with those in the literature. This method permits estimation of the local CMRglu under pathological conditions using regionally measured rate constants and provides new information on the pathophysiological meaning of the rate constants.

Aged↗
PubMed1984

[Quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow and local cerebral glucose utilization using 14C-IAP and 18F-FDG].

We have reported a quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using 14C-IAP and 18F-FDG respectively. Six awake normal rats and 3 left middle cerebral artery (MCA) occluded rats were used for this experiments. A 50-hold greater radioactivity of 18F was administered and the first exposure was done for 2 hours to obtain a 18F image. Three days later (39 half-lives of 18F), a second exposure was done for 5 to 6 days to obtain the 14C image. Tissue concentration of 14C was measured relative to the commercially available 14C-methyl methacrylate standards. 18F standards were prepared in each experiment. Cross contamination of 14C in the first exposure was less than 2% in the normal state and less than 4% even in the uncoupling condition. The values obtained by this methods for LCBF and LCGU agreed closely with those obtained by a single tracer technique previously reported in the literature. The technique outlined in this paper also provided local glucose utilization flow ratio (LGFR) for the first time. LGFR was obtained by dividing the LCGU image by LCBF image and was expressed as percent mumol/ml. The mean LGFR of control rats was 76 +/- 8% mumol/ml. In a MCA occlusion group, LGFR of ischemic cortex increased until 2 to 3 times higher than that of contralateral non-ischemic cortex. Oxygen glucose index image which was obtained from the LCGU and A-V differences of O2 showed that approximately half of the glucose was metabolized anerobically.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Pharmacokinetics of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in human brain tumors using positron emission tomography.

The nitrosoureas are widely used in the chemotherapy of brain tumors, two of the most common being 1,3-bis(2-chloroethyl)nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. However, we do not understand how these compounds work, nor do we know which part of the molecule has antitumor activity. In six patients with brain tumor, we measured the kinetic behavior of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in both the tumor and the normal brain with the aid of positron emission tomography; we also analyzed the distribution of radioactivity in plasma. We found the clearance of total radioactivity from the tumor to be significantly slower than from the contralateral brain and plasma, indicating a different rate of 1,3-bis(2-chloroethyl)nitrosourea decomposition in the tumor than in normal brain.

Brain Neoplasms↗
PubMed1983

New high-yield synthesis of 18F-labelled 2-deoxy-2-fluoro-D-glucose.

A new high-yield synthesis for the production of 18F-2-FDG has been developed by reacting 18F-labelled acetyl hypofluorite, prepared by in situ reaction of 18F-molecular fluorine with sodium acetate in glacial acetic acid, and tri-acetyl-D-glucal at room temperature. Molecular fluorine labelled with 18F was produced by a 20Ne(d, alpha) 18F reaction. 1,3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-D-glucopyranose is extracted with methylene chloride, evaporated to dryness and hydrolyzed, yielding 98% radiochemically pure 18F-2-FDG. Overall radiochemical yield is about 24 +/- 3%. The specific activity of the final product at the end of synthesis is about 25.38 GBq/mmol (685 mCi/mmol). The synthesis time is approximately 60 min. The synthesis proves that small medical cyclotrons are able to produce 18F-molecular fluorine at the levels needed for the synthesis of 18F-2-FDG used in functional imaging with positron emission tomography.

Deoxy Sugars↗
PubMed1983

An on-line synthesis of [15O]N2O: new blood-flow tracer for PET imaging.

This paper describes a recently developed on-line synthesis of a new blood-flow tracer, O-15-labeled nitrous oxide. The tracer was produced by catalytic oxidation of anhydrous ammonia in a gas mixture containing O-15-labeled molecular oxygen. (The oxygen-15 was produced by a 14N(d,n)15O reaction.) Anhydrous ammonia was mixed with the gas containing [15O]O2, and after preheating to about 200 degrees C was carried through an oven containing a Pt catalyst kept at about 310 degrees C. Labeled gas was purified in H3PO4 and KOH traps. O-15-labeled nitrous oxide was identified by gas radiochromatography and by various chemical reactions. Radiochemical purity of the O-15-labeled nitrous oxide exceeded 98%, radiochemical yield corrected for radioactioactive decay was 15-20%, and specific activity at the end of synthesis was about 50 mCi/mmole.

Nitrous Oxide↗
PubMedDate not supplied

alpha-Methyl tryptophan as a tracer for in vivo studies of brain serotonin system, from autoradiography to positron emission tomography.

The procedure for measuring the brain serotonin synthesis rate in living brain using labelled alpha-methyl-L-tryptophan (alpha-MTrp), a tryptophan analog, is described. This tracer could also be used for the anterograde axonal transport measurement of serotonin. One advantage of this method is that alpha-MTrp is converted in situ into a serotonin tracer, alpha-methyl serotonin, and should be distributed into the same compartments as serotonin.

Animals↗
PubMedDate not supplied

Image generation of serotonin synthesis rates using alpha-methyltryptophan and PET.

PURPOSE: We sought to create functional images of the serotonin (5-HT) synthesis rate obtained with alpha-[11C]methyl-L-tryptophan (alpha-MTrp) and PET and standardize them into the stereotaxic coordinate system. METHOD: Dynamic PET scans were performed in 11 healthy subjects after an injection of alpha-MTrp. Results obtained by the Patlak plot and nonlinear least-squares methods using arterial plasma as input function were compared. The pixel-by-pixel calculation of functional images of 5-HT synthesis was done by the Patlak plot approach, after results were compared by two methods. Input function obtained by combining venous plasma and sinus radioactivities was also evaluated as an alternative to arterial input function. RESULTS: There were no significant differences in 5-HT synthesis between the two calculation methods. The normalized venous input functions gave similar results as the arterial input function. The regional rates of 5-HT synthesis from functional images were not significantly different from those obtained by graphical plotting. CONCLUSION: alpha-MTrp images could be converted into functional images representing 5-HT synthesis rates in the living brain, facilitating statistical comparison.

Adult↗
PubMedDate not supplied

Use of short-lived 18F and long-lived 14C in double tracer autoradiography for simultaneous measurement of LCBF and LCGU.

We have developed a quantitative autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using a combination of 14C-long-lived and 18F-short-lived radionuclides as labels. To obtain the LCGU image, a 50-fold greater radioactivity of 18F than of 14C was administered and the first exposure was done for 2 hours. Three days later, when most of the 18F had decayed, a second exposure was done for 5 to 6 days to obtain the LCBF image. 18F standards were prepared in each experiment. The technique provides, for the first time, the local glucose flow ratio (LGFR). LGFR, obtained by dividing the LCGU by the LCBF image, was expressed as percent mumol/ml (multiplied by 100). Measurement of these three values in the same animal is expected to prove useful in the investigation of the pathophysiology of the brain. The advantages of this method are that cross contamination is less than 4%, chemical or physical manipulation of the slices is unnecessary, and final results can be obtained within a week.

Animals↗
PubMedDate not supplied

Correlation of local cerebral blood flow, glucose utilization, and tissue pH following a middle cerebral artery occlusion in the rat.

The use of three sets of the double-tracer autoradiographic technique to measure topographical changes of local cerebral blood flow (LCBF), glucose utilization (LCGU), and tissue pH following a 3 h middle cerebral artery (MCA) occlusion in the rat is described. In a sham-operated group of animals there was 10% reduction of LCBF and 7% reduction of LCGU in the most affected areas as compared to the contralateral homologous regions. However, the ratio of LCGU/LCBF in the affected areas remained within normal limits. In the MCA-occluded animals, LCGU showed a bimodal response to decreased LCBF. LCGU decreased with reduced LCBF until LCBF fell to 38% of normal. Below this LCBF level LCGU increased, most likely implying anerobic glycolysis. Decline of tissue pH corresponds to the mismatch of LCBF and LCGU. These results suggest that brain tissue pH change cannot be predicted on the basis of LCBF or LCGU alone.

Animals↗
PubMedDate not supplied

Simultaneous in vivo measurement of lumped constant and rate constants in experimental cerebral ischemia using F-18 FDG.

Lumped and transfer rate constants in ischemic brain tissue must be measured to estimate accurately cerebral glucose utilization by the deoxyglucose method. We studied the bilateral middle cerebral artery occlusion model in 17 cats, 5 with a 1-hour occlusion, 5 with a 4-hour occlusion, and 7 with a sham operation. The time course of cerebral tissue radioactivity (Ci*(t)) was monitored by external coincidence counting during a programmed infusion of [18F]-2-deoxy-2-fluoro-d-glucose (18F-2-FDG). Arterial plasma concentration (Cp*(t)) of the tracer was kept constant during the first 45 minutes. Rate constants were estimated from Ci*(t) and Cp*(t) by a nonlinear least-squares fitting routine. The lumped constant was estimated from the fit of the ratio of extraction fractions of glucose and 18F-2-FDG by nonweighted, nonlinear least-squares fitting. In the 4-hour-occlusion model, the transfer constant k1* was 23% lower, k3* 39% lower, and the lumped constant 78% higher than in the sham-operated animals. In the 1-hour-occlusion model, k3* was 26% lower than in the sham-operated animals but the lumped constant was not significantly different. The rate of glucose utilization was significantly different in the 4-hour-occlusion model compared to the sham-operated animals (48% decrease, p less than 0.05) but was not significantly different in the 1-hour-occlusion model.

Animals↗