Biomedical subjects

Mark A Mintun

Publications and source records attributed to Mark A Mintun.

23 records · Page 2Linked to original sources

PubMed2003

In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM.

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis( N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of (60)Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with (60)Cu-ATSM before initiation of therapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2-46 months). It was demonstrated that PET imaging with (60)Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible (60)Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for (60)Cu-ATSM was significantly lower in responders (1.5+/-0.4) than in nonresponders (3.4+/-0.8) (P=0.002). However, the mean SUV for (60)Cu-ATSM was not significantly different in responders (2.8+/-1.1) and nonresponders (3.5+/-1.0) ( P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M > or =3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with (60)Cu-ATSM uptake (r=0.04; P=0.9). (60)Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of (60)Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.

Aged↗

PubMed2003

Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response-a preliminary report.

PURPOSE: Tumor hypoxia is associated with poor response to therapy. We have investigated whether pretreatment tumor hypoxia assessed by positron emission tomography (PET) with Cu-60 diacetyl-bis(N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) predicts responsiveness to subsequent therapy in cervical cancer. METHODS AND MATERIALS: Fourteen patients with biopsy-proved cervical cancer were studied by PET with (60)Cu-ATSM before initiation of radiotherapy and chemotherapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M) and peak slope index of tumor tracer uptake. All patients also underwent clinical PET with F-18 fluorodeoxyglucose (FDG) before institution of therapy. The PET results were correlated with follow-up evaluation (14-24 months). RESULTS: Tumor uptake of (60)Cu-ATSM was inversely related to progression-free survival and overall survival (log-rank p = 0.0005 and p = 0.015, respectively). An arbitrarily selected T/M threshold of 3.5 discriminated those likely to develop recurrence; 6 of 9 patients with normoxic tumors (T/M < 3.5) are free of disease at last follow-up, whereas all of 5 patients with hypoxic tumors (T/M > 3.5) have already developed recurrence. Similar discrimination was achieved with the peak slope index. The frequency of locoregional nodal metastasis was greater in hypoxic tumors (p = 0.03). Tumor FDG uptake did not correlate with (60)Cu-ATSM uptake (r = 0.04; p = 0.80), and there was no significant difference in tumor FDG uptake between patients with hypoxic tumors and those with normoxic tumors. CONCLUSION: (60)Cu-ATSM-PET in patients with cervical cancer revealed clinically relevant information about tumor oxygenation that was predictive of tumor behavior and response to therapy in this small study.

Adult↗

PubMed2002

A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist.

Dopamine can induce fascinating, complex human behavioral states, including disinhibition, euphoria, or elaborate stereotypies, whereas dopamine deficiency can cause anxiety or sadness. Limited data suggest that these phenomena may involve dysfunction of orbital frontal cortex, cingulate cortex, or ventral striatum. The dopamine D3 receptor (D3R) has an anatomic distribution that suggests it could mediate these effects, but almost no data directly demonstrate the regional functional effects of D3R activation. We used quantitative positron emission tomography (PET), [15O]water, and the D3-preferring dopamine agonist pramipexole to identify D3-mediated regional cerebral blood flow (rCBF) responses in living primates. We studied seven normal baboons ventilated with 70% nitrous oxide, and analyzed results voxelwise in a common atlas space. At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance). Cortical areas related to movement were relatively unaffected, and rCBF did not change in cerebellum or visual cortex. The dose-response curve and duration of pramipexole's effects suggest that these rCBF responses indicate functional effects of a D3-preferring agonist. A D2-preferring agonist studied under the same conditions produced a quantitatively different pattern of responses. We conclude that a dopamine D3 receptor agonist preferentially affects brain activity in prefrontal and limbic cortex, and speculate that dopamine's effects on these regions via D3Rs may mediate some of the known psychiatric complications of dopamine deficiency or excess.

Animals↗

PubMed2002

Time-related increase of oxygen utilization in continuously activated human visual cortex.

Oxygen utilization increase is fractionally much less than that seen in glucose metabolism and blood flow soon after onset of neuronal activation, however its behavior during continued activation is less certain. We evaluated the effects of 25 min of visual stimulation on CBF, CMRO(2), and OEF using [(15)O] water and [(15)O] oxygen PET. Seven healthy volunteers underwent a PET session consisting of serial [(15)O] water and [(15)O] oxygen scans at the fixation-only baseline visual state and after 1, 13, and 25 min of the continuous visual stimulation using a black-white vertical grating. CBF, CMRO(2), and OEF values were calculated for the entire brain and for regions of interest in visual cortex centered over the area of activation. After 1 min of stimulation, CMRO(2) increased only 4.7% compared to baseline and CBF increased 40.7%. However, after 25 min of stimulation the increase in CMRO(2) compared to baseline was 15.0%, having tripled from that measured at 1 min (P < 0.05). CBF did not significantly change during this time. OEF was 48.3% at baseline. It decreased to 37.1% after 1 min of visual stimulation (P < 0.01) and then returned almost to baseline values after 25 min of activation OEF (45.7%). There were no significant variations in whole-brain values during the study. We suggest that in the activated brain, the increased energy demands initially are not fully met with oxidative metabolism and must predominantly be supported by increased glycolysis. With continued activation, oxygen utilization increases reducing the need for excess glycolysis.

Adult↗

PubMed2002

Greater loss of 5-HT(2A) receptors in midlife than in late life.

OBJECTIVE: Earlier work has shown markedly lower density of serotonin 2A (5-HT(2A)) receptors in elderly subjects than in young healthy subjects. In this study the authors used positron emission tomography (PET) and [(18)F]altanserin, a ligand with high affinity for the 5-HT(2A) receptor, to examine the relationship between 5-HT(2A) receptor density and age in more detail. METHOD: The 22 subjects ranged in age from 21 to 69 years (mean=43.4, SD=13.3) and were healthy comparison subjects in a study of depression. Regions of interest were determined on magnetic resonance images and were transferred to coregistered PET data. The data were derived from dynamic PET scanning and arterial sampling with resulting plasma activity data corrected for labeled metabolites. Compartmental modeling was used to estimate the radioligand distribution volume. By comparing the distribution volume (DV) of different regions to the cerebellum distribution volume, DV(ratio)-1, which is proportional to the binding potential, was calculated. RESULTS: The decrease in 5-HT(2A) binding was not linear but on average was approximately 17% per decade from age 20. The correlations between age and 5-HT(2A) DV(ratio)-1 were significant for the global measure and for the medial gyrus rectus, anterior cingulate, posterior medial prefrontal cortex, hippocampus, and occipital cortex. Most of the fall off in receptor binding occurred up through midlife, and there was less decrease in late life. There were no decreases in regional brain volumes of corresponding magnitudes. CONCLUSIONS: 5-HT(2A) receptor binding decreases dramatically in a variety of brain regions up through midlife.

Adult↗