Nan-Tsing Chiu

Prognostic Value of Whole-Body Total Lesion Glycolysis at Pretreatment FDG PET/CT in Non–Small Cell Lung Cancer

PURPOSE To determine whether whole-body total lesion glycolysis (TLG), which combines volumetric and metabolic information from fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), can provide a better evaluation of the prognosis for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. The authors identified 105 consecutive patients with NSCLC who underwent staging FDG PET/CT before any therapy. These patients were free of brain metastasis and underwent standard treatment and subsequent clinical follow-up. Metabolic tumor volume (MTV), mean standardized uptake value (SUV), and maximum SUV of each tumor over the whole body were determined. Whole-body MTV and whole-body TLG are the summation of all the MTVs and summation of individual tumor volume multiplied by its mean SUV, respectively. Univariate and multivariate analyses were performed to assess the prognostic significance of whole-body TLG and other factors, including whole-body MTV, lung TLG, lung MTV, maximum SUV, sex, age, performance status, histologic subtype, T stage, N stage, clinical stage, and treatment method. RESULTS The median follow-up time was 3.1 years. The estimated median progression-free survival (PFS) and overall survival (OS) for the cohort was 10.8 months and 2.8 years, respectively. The 1-year PFS was 0.0% for patients with high whole-body TLG (>655) and 50.0% for those with low whole-body TLG (≤655). The 1-year OS was 58.8% for patients with high whole-body TLG and 84.1% for those with low whole-body TLG. Univariate analysis showed that whole-body TLG, whole-body MTV, lung TLG, lung MTV, maximum SUV, performance status, T stage, N stage, clinical stage, and treatment type (surgery vs other) were significant prognostic factors for PFS (P < .01 for all). With use of the forward stepwise multivariate Cox proportional hazards model, whole-body TLG (hazard ratio = 2.92; 95% confidence interval: 1.62, 5.26; P < .01) and surgical treatment (hazard ratio = 4.24; 95% confidence interval: 2.54, 7.07; P < .01) remained significant in PFS. CONCLUSION Whole-body TLG is of prognostic value for NSCLC. It may be a promising tool for stratifying patients with NSCLC for risk-adapted therapies.

Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers--a SPECT study.

Recent lines of research suggest that, in addition to hypothalamic sites, the striatum dopaminergic system may be a target for regulating homeostasis that may be represented by the body mass index (BMI). Although it has been reported that the striatal dopamine receptor (DRD2) availability of very obese individuals was reduced in proportion to their BMI, the correlation between the striatal dopamine system and the BMI in healthy individuals remains unclear. To investigate this relationship, the striatal dopamine transporter (DAT) availability of 50 healthy volunteers was measured using single position emission computational topography (SPECT) and [99mTc]-TRODAT-1. The serum levels of sugar, C-peptide, insulin, glycosylated hemoglobin and leptin were measured. Our results showed that age and the BMI are significantly negatively associated with the striatal DAT availability. Moreover, BMI was the only significant predictor for striatal DAT availability. These results suggest that the striatal dopamine system may be involved in body mass index regulation. Thus, molecular imaging studies measuring the striatal DAT availability should consider the BMI, rather than age, as a covariant.

Dual-Phase 18F-FDG PET in the Diagnosis of Pulmonary Nodules with an Initial Standard Uptake Value Less Than 2.5

OBJECTIVE A cutoff standard uptake value (SUV) of 2.5 has been commonly adopted for (18)F-FDG PET to evaluate pulmonary lesions, but false results can occur. Studies have shown the usefulness of delayed PET for improving accuracy. This study was designed to examine the efficiency of delayed PET of pulmonary nodules with an initial mean SUV less than 2.5. MATERIALS AND METHODS Dual-phase FDG PET studies were conducted with imaging 1 and 2 hours after FDG injection, and pulmonary lesions with an initial mean SUV less than 2.5 were identified. Nodules with pathologic reports were included in the study. The differences in mean SUV, maximal SUV, and retention index between benign and malignant pulmonary lesions were analyzed. Receiver operating characteristic analysis was performed to evaluate the discriminating validity of the retention index. RESULTS A total of 31 lesions (15 benign, 16 malignant) were included in the study. Among the benign lesions, 12 were granulomatous inflammation, including 10 tuberculosis lesions and two cryptococcosis lesions, and three were focal fibrosis. A retention index greater than 0% was observed in 87% of the benign lesions; 60% of the benign lesions had a retention index greater than 10%. Among the malignant lesions, 75% had a retention index greater than 0%, and 62% had a retention index greater than 10%. We found no significant differences in mean SUV, maximal SUV, and retention index between benign and malignant lesions. The area under the receiver operating characteristic curve did not differ from 0.5. CONCLUSION Delayed FDG PET is not useful for differentiating benign and malignant pulmonary nodules with an initial mean SUV less than 2.5 in geographic regions with epidemic granulomatous disease such as tuberculosis or in patients at high risk of granulomatous inflammation.

Decreased dopamine transporter availability in male smokers — A dual isotope SPECT study

INTRODUCTION Although the mesolimbic dopaminergic system has been shown to play a role in reinforcing tobacco smoking, results of imaging studies that examine the relationship between tobacco smoking and the central dopamine system remain discrepant. To delineate the role of tobacco addiction in central pre- and post-synaptic dopaminergic activities, we analyzed the central D2-family receptors, the dopamine transporters (DAT), and degrees of dependence in male smokers. METHODS Eleven male smokers and 11 healthy non-smokers were recruited. The striatal dopamine D2/D3 receptor availability was approximated using SPECT and [123 I] IBZM while the DAT availability was approximated using SPECT and [99m Tc] TRODAT-1. All of the smokers completed the Fagerström Test for Nicotine Dependence (FTND) and other related questionnaires. RESULTS A decrease in DAT availability in the striatum of male smokers is noted (p<05). However, the striatal D2/D3 receptor availability in male smokers does not differ from that of non-smokers. CONCLUSIONS These findings suggest that cigarette smoking may alter central dopamine functions in males, particularly at the pre-synaptic sites.

Greater availability of dopamine transporters in patients with major depression — A dual-isotope SPECT study

In order to explore the neuropathology of the pre- and post-synaptic dopamine neurons of patients with major depression, we examined striatal D(2)/D(3) receptor uptake and dopamine transporter (DAT) availability simultaneously in drug-free depressed patients using a dual-isotope single photon emission computed tomography (SPECT) imaging technique. Ten unmedicated patients with unmediated depression and ten healthy controls were recruited. The striatal dopamine D(2)/D(3) receptor availability was measured using SPECT and [(123)I] IBZM, while DAT was measured using SPECT and [(99m)Tc] TRODAT-1. The symptom changes of the drug-free patients were reassessed after a 4-week antidepressant treatment. DAT binding in the patient group were significantly higher than in control group. That was not the case, however, for striatal D(2)/D(3) receptor availability. Pre-treatment striatal DAT availability correlated only marginally with changes in the Hamilton Depression Rating Scale after 4 weeks of treatment. Central dopamine functions may be altered in patients with major depression, particularly in the pre-synaptic sites.

Correlation between fine motor activity and striatal dopamine D2 receptor density in patients with schizophrenia and healthy controls.

Striatal dopamine D2 receptor density is an important indicator of many neuropsychiatric disorders and also of motor activity. This study examined the relationship between a fine motor task (finger tapping test, FTT) and striatal D2 dopamine receptor density by examining 20 healthy volunteers and 20 schizophrenic patients. Striatal D2 receptor density was determined with single photon emission computed tomography using [123I]IBZM (iodo-benzamide). The correlation between the FTT score and striatal D2 receptor density was statistically significant not only in the patient group but also in healthy controls. The FTT scores and striatal D2 receptor density were lower in medicated patients than that in healthy controls. Compared with the Simpson-Angus Scale scores, the FTT scores were more strongly associated with striatal D2 receptor density. The use of neuroleptic medication seemed to influence the associations between FTT scores and striatal D2 receptor density in the patient group. The FTT scores and striatal D2 receptor density were age-sensitive in healthy controls. FTT may be a more sensitive tool for detecting neuroleptic-induced motor impairment in patients with schizophrenia. The sensitivity of the FTT to age and neuroleptic effects may be explained in part by a decline in dopamine D2 density.

Availability of dopamine and serotonin transporters in opioid-dependent users—a two-isotope SPECT study

Rationale and objectiveThe aims of this study were to examine the differences between 32 opioid-dependent users treated with a very low dose of methadone or undergoing methadone-free abstinence and 32 controls.MethodsSPECT analysis using [99mTc] TRODAT-1 to assess striatal dopamine transporter (DAT) availability and [123I] ADAM to assess midbrain serotonin transporter (SERT) availability were performed.ResultsLower striatal DAT and midbrain SERT availabilities were noted in low-dose methadone users. History of metamphatamine use was associated with the lower striatal DAT. The striatal DAT of methadone-free abstainers was also lower than controls. The midbrain SERT availability tended to be higher in the methadone-free abstainers than the low-dose methadone users. The severity of depressive symptoms was negatively correlated with midbrain SERT availability in the opioid users.ConclusionThe availability of striatal DAT tended to be, and the availability of midbrain SERT was, lower in the opioid users. History of metamphatamine use may confound the difference in straital DAT between controls and opioid users, as midbrain SERT and depressive symptoms are also associated with opioid use and abstinence.

Association between cognitive performance and striatal dopamine binding is higher in timing and motor tasks in patients with schizophrenia

The basal ganglia have received increasing attention with regard to their role in time pacing, motor function and other components of cognition. The aim of this study was to test whether the finer the motor activity and/or time perception performance were, the higher the striatal dopamine D(2) binding would be. Single photon emission computed tomography (SPECT) with [(123)I]iodobenzamide (IBZM) was performed to measure striatal D(2) receptor densities. A battery of neuropsychological tests, including the Wisconsin Card Sorting Test (WCST), the finger tapping test (FTT), and an attention test, was performed by patients with schizophrenia. Results indicated a strong correlation between the FTT score and striatal D(2) receptor binding. Neuroleptic dosage plays an important role in the relationship between cognitive tasks and striatal dopamine receptor densities. In addition, the striatal D(2) receptor density is more significantly correlated with attentional tests that consider the time effect than those that do not. Among the three tests performed, the WCST was least significantly correlated with striatal D(2) receptor densities. A decrease in striatal dopamine D(2) receptor density seems to be associated with impaired performance on optimal timing tasks and motor processing in patients with schizophrenia.

Correlation between different memory systems and striatal dopamine D2/D3 receptor density: a single photon emission computed tomography study.

OBJECTIVE Although studies have indicated that the human basal ganglia have a specific role in different memory systems, the functional significance of the striatal dopamine activities for the basal ganglia remains less clear. This study assessed the relationship between measures of striatal dopamine activities and indices of different memory systems in healthy individuals. METHOD Single photon emission computed tomography and [123I]IBZM (iodobenzamide) were used to assess the striatal dopamine D2/D3 receptor density in 62 healthy volunteers aged between 19 and 61 years. All subjects underwent a Wechsler Memory Scale-Revised test. RESULTS Dopamine D2/D3 receptor densities in the striatum decline with age. Stepwise regression analysis showed that verbal delayed recall and working memory account for most of the variance in dopamine D2/D3 measurements. These relationships remain significantly after controlling for age effects. CONCLUSIONS Brain striatal dopamine activities are also significantly associated with various memory systems, in addition to motor functions. This may explain why patients with neuropsychiatric disorders may have both memory and motor impairments.

Correlation between striatal dopamine D2 receptor density and neuroticism in community volunteers

The central dopaminergic system, as well as the central serotonergic system, has been reported to be correlated with higher neuroticism. The present study examined the relationship between striatal dopamine D(2) receptor density and neuroticism. Neuroticism was assessed with the Maudsley Personality Inventory, and psychiatric morbidity was evaluated with both the Mini International Neuropsychiatric Interview and the Hamilton Depression Rating Scale (HAM-D). Single photon emission computed tomography with [(123)I]iodo-benzamide was used to measure striatal dopamine D(2) receptor density. HAM-D scores and psychiatric morbidity in high-neuroticism individuals were higher than in low-neuroticism individuals. Moreover, striatal dopamine D(2) receptor densities were significantly correlated with the neuroticism score of the 41 subjects. The central dopaminergic system may play an important role in the neurobiological characteristics of neuroticism.