Biomedical subjects

J M Link

Publications and source records attributed to J M Link.

At least 19 recordsLinked to original sources

PubMed2005

Measurement of the D(s)+ lifetime.

A high statistics measurement of the D(s)+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis of the two decay modes, D(s)+ --> phi(1020)pi+ and D(s)+ -->K*(892)0K+, used for the measurement. The measured lifetime is 507.4 +/- 5.5(stat) +/- 5.1(syst) fs using 8961 +/- 105 D(s)+ --> phi(1020)pi+ and 4680 +/- 90 D(s)+ --> K*(892)0K+ decays. This is a significant improvement over the present world average.

Journal Article↗

PubMed2002

A high statistics measurement of the Lambda(+)(c) lifetime.

A high statistics measurement of the Lambda(+)(c) lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat) +/- 2.5 (syst) fs from 8034 +/- 122 Lambda(+)(c)-->pK(-)pi(+) decays represents a significant improvement over the present world average.

Journal Article↗

PubMed2002

Search for CP violation in the decays D+--> K(S)pi+ and D+-->K(S)K+.

A high-statistics sample of photoproduced charm from the FOCUS experiment has been used to search for direct CP violation in the decay rates for D+-->K(S)pi+ and D+-->K(S)K+. We have measured the following asymmetry parameters relative to D+-->K-pi+pi+: A(CP)(K(S)pi+) = (-1.6+/-1.5+/-0.9)%, A(CP)(K(S)K+) = (+6.9+/-6.0+/-1.5)%, and A(CP)(K(S)K+) = (+7.1+/-6.1+/-1.2)% relative to D+-->K(S)pi+. We have also measured the relative branching ratios and found Gamma(D+-->K(0)pi+)/Gamma(D+-->K-pi+pi+) = (30.60+/-0.46+/-0.32)%, Gamma(D+-->K(0)K+)/Gamma(D+-->K-pi+pi+) = (6.04+/-0.35+/-0.30)%, and Gamma(D+-->K(0)K+)/Gamma(D+-->K(0)pi+) = (19.96+/-1.19+/-0.96)%.

Journal Article↗

PubMed2001

Measurement of the branching ratios of D(+) and D(+)(s) hadronic decays to four-body final states containing a K(S).

We have studied hadronic four-body decays of D(+) and D(+)(s) mesons with a K(S) in the final state using data recorded during the 1996-1997 fixed-target run of the Fermilab high energy photoproduction experiment FOCUS. We report a new branching ratio measurement of gamma(D(+)-->K(S)K-pi(+)pi(+))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0768+/-0.0041+/-0.0032. We make the first observation of three new decay modes with branching ratios gamma(D(+)-->K(S)K+pi(+)pi(-))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0562+/-0.0039+/-0.0040, gamma(D(+)-->K(S)K+K-pi(+))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0077+/-0.0015+/-0.0009, and gamma(D(+)(s)-->K(S)K+pi(+)pi(-))/gamma(D(+)(s)-->K(S)K-pi(+)pi(+)) = 0.586+/-0.052+/-0.043, where in each case the first error is statistical and the second error is systematic.

Journal Article↗

PubMed2001

Study of the decay D0 --> K+pi-.

Using a large sample of photoproduced charm mesons from the FOCUS experiment at Fermilab (FNAL-E831), we observe the decay D0-->K+pi- with a signal yield of 149+/-31 events compared to a similarly cut sample consisting of 36 760+/-195 D0-->K-pi+ events. We use the observed ratio of D0-->K+pi- to D0-->K-pi+ (0.404+/-0.085+/-0.025)% to obtain a relationship between the D0 mixing and doubly Cabibbo suppressed decay parameters.

Journal Article↗

PubMed2001

Kinetic characterization of hexokinase isoenzymes from glioma cells: implications for FDG imaging of human brain tumors.

Quantitative imaging of glucose metabolism of human brain tumors with PET utilizes 2-[(18)F]-fluorodeoxy-D-glucose (FDG) and a conversion factor called the lumped constant (LC), which relates the metabolic rate of FDG to glucose. Since tumors have greater uptake of FDG than would be predicted by the metabolism of native glucose, the characteristic of tumors that governs the uptake of FDG must be part of the LC. The LC is chiefly determined by the phosphorylation ratio (PR), which is comprised of the kinetic parameters (Km and Vmax) of hexokinase (HK) for glucose as well as for FDG (LC proportional to (Km(glc) x Vmax(FDG))/(Km(FDG) x Vmax(glc)). The value of the LC has been estimated from imaging studies, but not validated in vitro from HK kinetic parameters. In this study we measured the kinetic constants of bovine and 36B-10 rat glioma HK I (predominant in normal brain) and 36B-10 glioma HK II (increased in brain tumors) for the hexose substrates glucose, 2-deoxy-D-glucose (2DG) and FDG. Our principal results show that the KmGlc < KmFDG << Km2DG and that PR2DG < PRFDG. The FDG LC calculated from our kinetic parameters for normal brain, possessing predominantly HK I, would be higher than the normal brain LC predicted from animal studies using 2DG or human PET studies using FDG or 2DG. These results also suggest that a shift from HK I to HK II, which has been observed to increase in brain tumors, would have little effect on the value of the tumor LC.

Animals↗

PubMed2001

[18F]fluoroestradiol radiation dosimetry in human PET studies.

UNLABELLED: [18F]16alpha-fluoroestradiol (FES) is a PET imaging agent useful for the study of estrogen receptors in breast cancer. We estimated the radiation dosimetry for this tracer using data obtained in patient studies. METHODS: Time-dependent tissue concentrations of radioactivity were determined from blood samples and PET images in 49 patients (52 studies) after intravenous injection of FES. Radiation absorbed doses were calculated using the procedures of the MIRD committee, taking into account the variation in dose based on the distribution of activities observed in the individual patients. Effective dose equivalent was calculated using International Commission on Radiological Protection Publication 60 weights for the standard woman. RESULTS: The effective dose equivalent was 0.022 mSv/MBq (80 mrem/mCi). The organ that received the highest dose was the liver (0.13 mGy/MBq [470 mrad/mCi]), followed by the gallbladder (0.10 mGy/MBq [380 mrad/mCi]) and the urinary bladder (0.05 mGy/MBq [190 mrad/mCi]). CONCLUSION: The organ doses are comparable to those associated with other commonly performed nuclear medicine tests. FES is a useful estrogen receptor-imaging agent, and the potential radiation risks associated with this study are well within accepted limits.

Adult↗

PubMed1999

Whole-column radioactivity detection: simultaneous separation and enhanced detectability.

The development of a whole-column radiation detector for measurement and separation of low amounts of beta emitting analytes is described. The design of this detector is unique with all of the chromatography media located within the detector volume. This whole-column design provides the advantage of increased radiation signal without loss of chromatographic efficiency, which translates to increased detectability. This increase was compared theoretically with flow-through radiation detection, and the theory was tested experimentally. Using two analytes, carbon-11-labeled m-hydroxyephedrine and alpha-methylepinephrine, only 3 and 8 Bq (80 and 220 pCi), respectively, were needed to obtain a 10% coefficient of variation using whole-column detection. For [11C]-m-hydroxyephedrine, 100 times more radioactivity was required to achieve the same coefficient of variation using flow-through detection. A limit of detection (LD) for the analytes of 2 Bq (54 pCi) was obtained for whole-column detection, an improvement of 50 in LD compared with flow-through detection. Signal improvement increased linearly with the chromatographic resolution. The whole-column detection method is robust and applicable to many chromatographic separations.

Carbon Radioisotopes↗

PubMed1999

2-[C-11]thymidine imaging of malignant brain tumors.

Malignant brain tumors pose diagnostic and therapeutic problems. Despite the advent of new brain imaging modalities, including magnetic resonance imaging (MRI) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), determination of tumor viability and response to treatment is often difficult. Blood-brain barrier disruption can be caused by tumor or nonspecific reactions to treatment, making MRI interpretation ambiguous. The high metabolic background of the normal brain and its regional variability makes it difficult to identify small or less active tumors by FDG imaging of cellular energetics. We have investigated 2-[C-11]thymidine (dThd) and PET to image the rate of brain tumor cellular proliferation. A series of 13 patients underwent closely spaced dThd PET, FDG PET, and MRI procedures, and the image results were compared by standardized visual analysis. The resulting dThd scans were qualitatively different from the other two scans in approximately 50% of the cases, which suggests that dThd provided information distinct from FDG PET and MRI. In two cases, recurrent tumor was more apparent on the dThd study than on FDG; in two other patients, tumor dThd uptake was less than FDG uptake, and these patients had slower tumor progression than the three patients with both high dThd and FDG uptake. To better characterize tumor proliferation, kinetic modeling was applied to dynamic dThd PET uptake data and metabolite-analyzed blood data in a subset of patients. Kinetic analysis was able to remove the confounding influence of [C-11]CO2, the principal labeled metabolite of 2-[C-11]dThd, and to estimate the flux of dThd incorporation into DNA. Sequential, same-day [C-11]CO2 and [C-11]dThd imaging demonstrated the ability of kinetic analysis to model both dThd and CO2 simultaneously. Images of dThd flux obtained using the model along with the mixture analysis method for pixel-by-pixel parametric imaging significantly enhanced the contrast of tumor compared with normal brain. Comparison of model estimates of dThd transport versus dThd flux was able to discern increased dThd uptake simply on the basis of blood-brain barrier disruption retention on the basis of increased cellular proliferation. This preliminary study demonstrates the potential for imaging brain tumor cellular proliferation to provide unique information for guiding patient treatment.

Astrocytoma↗

PubMed1999

Kinetic analysis of 2-[11C]thymidine PET imaging studies: validation studies.

UNLABELLED: 2-[11C]thymidine has been tested as a PET tracer of cellular proliferation. We have previously described a model of thymidine and labeled metabolite kinetics for use in quantifying the flux of thymidine into DNA as a measure of tumor proliferation. We describe here the results of studies to validate some of the model's assumptions and to test the model's ability to predict the time course of tracer incorporation into DNA in tumors. METHODS: Three sets of studies were conducted: (a) The uptake of tracers in proliferative tissues of normal mice was measured early after injection to assess the relative delivery of thymidine and metabolites of thymidine catabolism (thymine and CO2) and calculate relative blood-tissue transfer rates (relative K1s). (b) By using sequential injections of [11C]thymidine and [11C]thymine in normal human volunteers, the kinetics of the first labeled metabolite were measured to determine whether it was trapped in proliferating tissue such as the bone marrow. (c) In a multitumor rat model, 2-[14C]thymidine injection, tumor sampling and quantitative DNA extraction were performed to measure the time course of label uptake into DNA for comparison with model predictions. RESULTS: Studies in mice showed consistent relative delivery of thymidine and metabolites in somatic tissue but, as expected, showed reduced delivery of thymidine and thymine in the normal brain compared to CO2. Thymine studies in volunteers showed only minimal trapping of label in bone marrow in comparison to thymidine. This quantity of trapping could be explained by a small amount of fixation of labeled CO2 in tissue, a process that is included as part of the model. Uptake experiments in rats showed early incorporation of label into DNA, and the model was able to fit the time course of uptake. CONCLUSION: These initial studies support the assumptions of the compartmental model and demonstrate its ability to quantify thymidine flux into DNA by using 2-[11C]thymidine and PET. Results suggest that further work will be necessary to investigate the effects of tumor heterogeneity and to compare PET measures of tumor proliferation to in vitro measures of proliferation and to clinical tumor behavior in patients undergoing therapy.

Animals↗

PubMed1998

Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant.

UNLABELLED: Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. METHODS: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. RESULTS: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46 (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). CONCLUSION: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

Autoradiography↗

PubMed1998

Kinetic analysis of 2-[carbon-11]thymidine PET imaging studies: compartmental model and mathematical analysis.

UNLABELLED: Carbon-11-thymidine is a PET tracer of DNA synthesis and cellular proliferation. Quantitative analysis of [11C]thymidine images is complicated by the presence of significant quantities of labeled metabolites. Estimation of the rate of thymidine incorporation into DNA using [11C]thymidine requires a kinetic model that is capable of describing the behavior of thymidine and labeled metabolites. METHODS: Based on previous studies with labeled thymidine, we constructed a five-compartment model describing the kinetic behavior of 2-[11C]thymidine and its labeled metabolites. In addition, we have performed a series of calculations and simulations to calculate the sensitivity and identifiability of model parameters to estimate the extent to which individual parameters can be estimated; to determine appropriate model constraints necessary for reproducible estimates of the constant describing flux of thymidine from the blood into DNA, i.e., thymidine flux constant; and to determine the potential accuracy of model parameter and thymidine flux constant estimates from PET imaging data. RESULTS: The underlying assumptions in the thymidine compartmental model lead to a description of the thymidine flux constant for DNA incorporation in terms of model parameters. Sensitivity and identifiability analyses suggest that the model parameters pertaining to labeled metabolites will be difficult to estimate independently of the thymidine parameters. Exact evaluation of the kinetic parameters of the labeled metabolites is not the principal goal of this model. Simulations were performed that suggest that it is preferable to tightly constrain these parameters to preset values near the center of their expected ranges. Although it is difficult to estimate individual thymidine model parameters, the flux constant for incorporation into DNA can be accurately estimated (r > 0.9 for estimated versus true simulated flux constant). Flux constant estimates are not affected by modest levels of local degradation of thymidine that may occur in proliferating tissue. CONCLUSION: By using a kinetic model for thymidine and labeled metabolites, it is possible to estimate the flux of thymidine uptake and incorporation into DNA and, thereby, noninvasively estimate regional cellular proliferation using [11C]thymidine and PET.

Carbon Radioisotopes↗

PubMed1998

Quantitation of presynaptic cardiac sympathetic function with carbon-11-meta-hydroxyephedrine.

UNLABELLED: The purpose of this study was to validate an axially distributed blood-tissue exchange model for the quantitation of cardiac presynaptic sympathetic nervous system function that could be applied to PET images. The model accounts for heterogeneity in myocardial blood flow, differences in transport rates of 11C-meta-hydroxyephedrine (mHED) across the capillary endothelium and/or neuronal membranes, the virtual volumes of distribution in the interstitial space and neuron and retention of mHED in the neuronal vesicles. METHODS: Multiple indicator outflow dilution and residue detection methods were used to measure the kinetics of radiolabeled intravascular space and interstitial space markers and 11C-mHED in isolated perfused rat heart at baseline and during norepinephrine neuronal transporter blockade with desipramine (DMI). The outflow dilution and residue detection data were modeled with a multiple pathway, four-region, axially distributed model of blood-tissue exchange describing flow in the capillary and exchange between regions using permeability-surface area products with units of clearance of milliliters per minute per gram. Meta-hydroxyephedrine may enter the nerve terminal via membrane transport, where it may be sequestered by first-order unidirectional uptake within vesicles. Release of mHED from the vesicles is modeled via exchange with the interstitial space. RESULTS: After intracoronary injection, mHED transport across the capillary endothelium and in the interstitial space closely followed that of sucrose. Subsequently, mHED was retained in the heart, whereas sucrose washed out rapidly. With DMI the outflow dilution curves more closely resembled those of sucrose. Model parameters reflecting capillary-interstitial kinetics and volumes of distribution were unchanged by DMI, whereas parameters reflecting the neuronal transporter process and volumes of distribution in the nerve terminal and vesicular sequestration were markedly decreased by DMI. Application of the model to a pilot set of canine PET images of mHED suggests the feasibility of this approach. CONCLUSION: Meta-hydroxyephedrine kinetics in the heart can be quantitated using an axially distributed, blood-tissue exchange model that accounts for heterogeneity of flow, reflects changes in neuronal function and is applicable to PET images.

Adrenergic Uptake Inhibitors↗

PubMed1998

Carbon-11-thymidine and FDG to measure therapy response.

UNLABELLED: This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS: In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

1-[Carbon-11]-glucose radiation dosimetry and distribution in human imaging studies.

UNLABELLED: 1-[Carbon-11]-D-glucose ([11C]-glucose) is an important imaging agent for PET studies that have been used to study the normal brain, encephalitis, epilepsy, manic-depressive disorder, schizophrenia and brain tumors. METHODS: Dosimetry estimates were calculated in subjects undergoing imaging studies to help define the radiation risk of [11C]-glucose PET imaging. Time-dependent radioactivity concentrations in normal tissues in 33 subjects after intravenous injection of [11C]-glucose were obtained by PET imaging. Radiation absorbed doses were calculated according to the procedures of the Medical Internal Radiation Dose (MIRD) committee along with the variation in dose based on the calculated standard deviation of activity distribution seen in the individual patients. RESULTS: Total body exposure was a median of 3.0 microGy/MBq in men and 3.8 microGy/MBq in women. The effective dose equivalent was 3.8 microGy/ MBq in men and 4.8 microGy/MBq in women. The critical organs were those that typically take up the most glucose (brain, heart wall and liver). CONCLUSION: The organ doses reported here are small and comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this radiotracer are within generally accepted limits.

Carbon Radioisotopes↗

PubMed1997

High speed liquid chromatography of phenylethanolamines for the kinetic analysis of [11C]-meta-hydroxyephedrine and metabolites in plasma.

A method is developed and described for analysis of [11C]-meta-hydroxyephedrine, [11C]MHED, a tracer of cardiac function, and its metabolites in plasma samples. The method combines on-column solid-phase extraction and separation on a single weak cation-exchange column. Phenylethanolamines were used to develop the separation method that concentrates the analytes on-column from physiological saline and then elutes them by changing to an acidic mobile phase. Hydrophobic interactions determine the selectivity, and elution order is the same as for reversed-phase liquid chromatography on a C1 stationary phase. The mechanism of separation is mixed mode, with ion-exchange coupled with a reversed-phase liquid chromatography mechanism. Each sample analysis requires only 10 min and does not require deproteinization or the use of organic solvents. In human samples, a single plasma metabolite of [11C]MHED along with the parent compound were observed using this method. The method was sufficiently rapid so that in 70 min seven samples were assayed, providing a well-defined time course for MHED and its metabolites in blood. The metabolite concentration increased with time to approximately 85% of the plasma activity 50 min after administration. The results with the developed method are comparable to those described for reversed-phase separations, with the advantage that our method does not require deproteinization, reducing sample analysis time by a factor of two.

Carbon Radioisotopes↗

PubMed1997

Production of [11C]CH3I by single pass reaction of [11C]CH4 with I2.

We report a single pass gas phase route to [11C]CH3I based on production of I from I2 at elevated temperature. I abstracts H from CH4 to yield CH3, which reacts with I2 to form CH3I. A fiber optic spectrometer was used to measure the I2 vapor concentration. [11C]CH3I yield increased with I2 concentration until excessive amounts of condensed I2 began to trap the 11C. The yield of [11C]CH3I was > 50% from [11C]CH4I; its specific activity was 12,000 Ci/mmole. The synthesis takes only 4 min after 11CH4 production and can be repeated without system cleanup.

Carbon Radioisotopes↗

PubMed1997

Feasibility of imaging pentose cycle glucose metabolism in gliomas with PET: studies in rat brain tumor models.

UNLABELLED: The feasibility of imaging pentose cycle (PC) glucose utilization in human gliomas with PET was explored in two rat glioma models by means of glucose radiolabeled in either the carbon-1 (C-1) or carbon-6 (C-6) position. METHODS: In vitro, monolayers of T-36B-10 glioma, tissue slices of intracerebral glioma grafts or slices of normal brain were fed [1-14C]glucose or [6-14C]glucose, and the generated [14C]CO2 was trapped to quantitate the ratio of [14C]CO2 from 14C-1 versus 14C-6. In vivo, rats bearing grafts of either T-36B-10 or T-C6 rat gliomas at six subcutaneous sites received simultaneous intravenous injections of either [1-11C]glucose and [6-14C]glucose, or [1-14C]glucose and [6-11C]glucose. Tumors were excised between 5 and 55 min postinjection to quantify tracer uptake while arterial plasma was collected to derive time-activity input curves. RESULTS: In vitro, the C-1/C-6 ratio for CO2 production from T-36B-10 monolayers was 8.8 +/- 0.4 (s.d.), in glioma slices it was 6.1 +/- 2.1 and in normal brain slices it was 1.1 +/- 0.7. PC metabolism in T-36B-10 was 1.8% +/- 0.5 of total glucose utilization. In vivo, tumor radioactivity levels normalized by plasma isotopic glucose levels showed that retained C-1 relative to C-6 radiolabeled glucose was significantly lower in both gliomas, 4.9% lower in T-36B-10 (p < 0.01) and 4.7% lower in T-C6 (p < 0.01). In an additional group of rats bearing T-36B-10 gliomas and exposed to 10 Gy of 137Cs irradiation 4 hr before isotope injection, the C-1 level was 5.6% lower than that for C-6 (p < 0.05). These results were analyzed with a model of glucose metabolism that simultaneously optimized parameters for C-1 and C-6 glucose kinetics by simulating the C-1 and C-6 tumor time-activity curves. The rate constant for loss of radiolabeled carbon from the tumors, k4, was higher for C-1 than for C-6 in all groups of rats (19% higher for T-36B-10 unirradiated, 32% for T-36B-10 irradiated and 32% for T-C6 unirradiated). CONCLUSION: Mathematical modeling, Monte Carlo simulations and construction of receiver-operator-characteristic curves show that if human gliomas have a similar fractional use of the PC, it should be measurable with PET using sequential studies with [1-11C]glucose and [6-11C]glucose.

Animals↗