Badreddine Bencherif

Imaging brain mu-opioid receptors in abstinent cocaine users: Time course and relation to cocaine craving

BACKGROUND Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [11C]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence. METHODS Regional brain mOR binding potential (BP) was measured with [11C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects. RESULTS Mu-opioid receptor BP was increased in the frontal, anterior cingulate, and lateral temporal cortex after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first two regions after 1 week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan. CONCLUSIONS These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement.

Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: A comprehensive evaluation

Positron emission tomography (PET) using F-18 fluoro-3′-deoxy-3-L-fluorothymidine (FLT) offers noninvasive assessment of cell proliferation in vivo. The most important application refers to the evaluation of tumour proliferative activity, representing a key feature of malignancy. Most data to date suggest that FLT is not a suitable biomarker for staging of cancers. This is because of the rather low fraction of tumour cells that undergo replication at a given time with subsequently relatively low tumour FLT uptake. In addition, generally, the high FLT uptake in liver and bone marrow limits the diagnostic use. We describe the current status on preclinical and clinical applications of FLT-PET including our own experience in brain tumours. The future of FLT-PET probably lies in the evaluation of tumour response to therapy and more importantly, in the prediction of early response in the course of treatment. The level of FLT accumulation in tumours depends on thymidine kinase 1 activity and on the therapy-induced activation of the salvage pathway and expression of nucleoside transporters. Therefore, cytostatic agents that cause arrest of the cell cycle in the S-phase may initially increase FLT uptake rather than reducing the tumour cell accumulation. In addition, agents that block the endogenous thymidine pathway may lead to overactivity of the salvage pathway and increase tumour FLT uptake. In contrast, many therapeutic agents inhibit both pathways and subsequently reduce tumour FLT uptake. Further studies comparing FLT with F-18 fluorodeoxyglucose-PET will be important to determine the complementary advantage of FLT-PET in early cancer therapy response assessment. Further research should be facilitated by simplified synthesis of FLT with improved yields and an increasing commercial availability.

Mu-opioid receptor binding measured by [11C]carfentanil positron emission tomography is related to craving and mood in alcohol dependence

BACKGROUND The endogenous opioid system has been linked to alcohol dependence through animal and human studies. We investigated the relationship between alcohol craving and brain mu opioid receptors (mu-OR) in alcohol-dependent subjects. METHODS Regional brain mu-OR binding potential (BP) was measured using [(11)C]carfentanil positron emission tomography in eight male alcohol-dependent subjects undergoing alcohol withdrawal and eight matched control subjects. Self-reported alcohol craving, withdrawal, and mood were measured. RESULTS Lower mu-OR BP was associated with higher craving in the right dorsal lateral prefrontal cortex, the right anterior frontal cortex, and right parietal cortex. In these regions, alcoholics showed lower mean mu-OR BP compared with control subjects. Mu-OR BP in four other brain regions also correlated with craving, but there were no group differences in receptor binding potential. Mu-OR BP also correlated with depressive symptoms in five brain regions, three of which were identified in the craving analyses. CONCLUSIONS Results show a strong functional relationship between alcohol craving, mood, and mu-OR binding in specific brain regions of recently abstinent, alcohol-dependent men.

Localization of Parathyroid Adenomas by Sonography and Technetium Tc 99m Sestamibi Single-Photon Emission Computed Tomography Before Minimally Invasive Parathyroidectomy Are Both Studies Really Needed?

Objective. The purpose of this study was to determine the utility of radiologist‐performed sonography as the principal modality for parathyroid localization before minimally invasive parathyroidectomy. Methods. Both sonography and technetium Tc 99m sestamibi single‐photon emission computed tomography (SPECT) are commonly performed during imaging evaluation of patients with primary hyperparathyroidism (HPTH). Sonographic examinations ordered during the study period were performed by 1 author (M.E.T.), and results were immediately reported. Findings of a subsequent Tc 99m sestamibi study were recorded blinded to the sonographic results. The sensitivity and specificity of sonography and Tc 99m sestamibi SPECT were assessed with the use of surgery and pathology reports as a reference standard. The 2007 global Medicare reimbursement rates were used to assess the costs of preoperative localization. Results. Parathyroidectomy was performed in 144 of 172 patients evaluated by both modalities. The sensitivity, specificity, and positive predictive value of sonography for identifying abnormal parathyroid glands were 74%, 96%, and 90%, respectively. Sonography correctly localized a single adenoma or suggested multiglandular disease in 112 of 144 patients (78%). The sensitivity, specificity, and positive predictive value of SPECT were 58%, 96%, and 89%. Technetium 99m sestamibi SPECT correctly predicted an adenoma or multiglandular disease in 88 of 144 patients (61%). Five patients with negative sonographic findings were shown to have uniglandular disease on Tc 99m sestamibi SPECT. Selective use of Tc 99m sestamibi SPECT (ie, when sonographic findings were negative or equivocal) would have decreased the cost of imaging by 53%. Conclusions. Radiologist‐performed sonography may potentially be used as a principal imaging modality for patients with HPTH. Selective use of Tc 99m sestamibi in cases with negative or equivocal sonographic findings can decrease the cost of imaging before parathyroid resection considerably.

Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients

BACKGROUND Cocaine users not seeking treatment have increased regional brain mu-opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown. METHODS We determined whether regional brain mOR binding before treatment correlates with outcome and compared it with standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine abstinence reinforcement, whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography with [¹¹C]]-carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment; and 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology. RESULTS Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sublobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use. CONCLUSIONS Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction.

Standardized uptake value-based evaluations of solitary pulmonary nodules using F-18 fluorodeoxyglucose-PET/computed tomography

ObjectiveCombined positron emission tomography and computed tomography (PET/CT) might improve the accuracy of PET tracer quantification by providing the exact tumour contour from coregistered CT images. We compared various semiquantitative approaches for the characterization of solitary pulmonary nodules (SPNs) using F-18 fluorodeoxyglucose PET/CT. MethodsThe final diagnosis of 49 SPNs (46 patients) was based on histopathology (n=33) or patient follow-up (n=16). The regions of interest (ROIs) were drawn around lesions based on the CT tumour contour and mirrored to the coregistered PET images. Quantification of F-18 fluorodeoxyglucose uptake was accomplished by calculating the standardized uptake value (SUV) using three different methods based on: activity from the maximum-valued pixel within the tumour (SUV-max); the mean ROI activity within the transaxial slice containing the maximum-valued pixel (SUV-mean); and the mean activity over the full tumour volume (SUV-vol). SUVs were corrected for partial volume effects and normalized by body surface area, lean body weight, and blood glucose. Recovery coefficients for partial-volume correction were derived from phantom studies. The ability of various SUVs to differentiate between benign and malignant SPNs was determined by calculating the area under the receiver operating characteristic (ROC) curves. ResultsTwenty-six SPNs were malignant and 23 were benign. The area under the ROC curve was 0.78 for SUV-mean, 0.83 for SUV-max, and 0.78 for SUV-vol. SUV-max and its normalizations yielded the highest area under the ROC curve (0.83–0.85); SUV-mean-partial volume corrected-lean body weight resulted in the lowest area under the ROC curve (0.76). At a specificity of 80%, SUV-max-body surface area provided the highest sensitivity (81%) and accuracy (80%) to detect malignant SPN. Using SUV-max with a cutoff of 2.4 at a specificity of 80% resulted in a sensitivity of 62% (accuracy 71%). ConclusionVarious normalizations applied to SUV-max provided the highest diagnostic accuracy for characterization of SPNs. Quantification methods using the exact tumour contour derived from CT in combined PET/CT imaging (ROI mean activity within a single transaxial slice and mean tumour volume activity) did not result in improved differentiation between benign and malignant SPN. Obtaining SUV-max might be sufficient in the clinical setting.

Dicyclomine: cause of abnormally decreased gall bladder ejection with sincalide-stimulated hepatobiliary scintigraphy.

Hepatobiliary scintigraphy with sincalide stimulation is a commonly performed examination to evaluate gall bladder function. The importance of fasting and the possible interference by opioids are well-known considerations in the preparation of patients for this study. We present another medication, dicyclomine, that may interfere with the validity of the results. A 16-year-old girl with abdominal pain underwent hepatobiliary scintigraphy with sincalide stimulation that demonstrated a decreased gall bladder ejection fraction of 3%. Because of concern for the potential anticholinergic effect of dicyclomine therapy, this medication was discontinued, and a repeat examination revealed a normal ejection fraction of 97%.