Whole-body metabolic tumour volume of 18F-FDG PET/CT improves the prediction of prognosis in small cell lung cancer.

PURPOSE: We investigated whether the whole-body metabolic tumour volume (WBMTV) measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can improve the prediction of prognosis in patients with small cell lung cancer (SCLC). METHODS: We reviewed 106 consecutive patients (mean age 67 years, range 42-89 years, limited stage 45 patients, extensive stage 61 patients) with pathologically proven SCLC who underwent pretreatment FDG PET/CT. WBMTV and maximum standardized uptake value (SUV(max)) were measured in all malignant lesions. The Cox proportional hazards model was used with age, sex, performance status, lactate dehydrogenase (LDH), treatment, stage, SUV(max) and WBMTV to predict overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed using WBMTV combined with conventional staging and tumour node metastasis (TNM) staging. RESULTS: The uni- and multivariate analyses showed that both stage and WBMTV were independent prognostic factors for death and progression. Patients with high WBMTV were associated with poor prognosis compared with patients with low WBMTV [hazard ratio = 2.11 (95% confidence interval 1.31-3.39) for death (p = 0.002) and 1.80 (95% confidence interval 1.16-2.80) for progression (p = 0.009)]. Incorporation of conventional staging and WBMTV could classify four subgroups with different prognoses (log-rank test, p < 0.001). Incorporation of TNM staging and WBMTV could classify six subgroups with different prognoses (log-rank test, p < 0.001). CONCLUSION: WBMTV is an independent predictor for progression and death in patients with SCLC. Incorporation of WBMTV with TNM staging can provide a more detailed prediction of prognosis than WBMTV with conventional staging as well as tumour staging alone.

Recurrence detection in differentiated thyroid cancer patients with elevated serum level of antithyroglobulin antibody: special emphasis on using (18)F-FDG PET/CT.

OBJECTIVE: A clinical challenge is presented by differentiated thyroid cancer (DTC) patients who show increased serum antithyroglobulin antibody (TgAb) level with undetectable thyroglobulin (Tg) and negative radioiodine whole body scan (I-WBS). The aim of this study is to investigate the recurrence in DTC patients with elevated TgAb by using (18)F-FDG PET/CT (PET/CT) in addition to I-WBS and neck ultrasonography (USG). SUBJECTS AND DESIGN: A total of 276 TgAb+ patients were enrolled. Recurrence was assessed and compared between TgAb+ and TgAb- patients. TgAb+ patients were further categorized into two groups of 35-140 U/ml (Group A) and 140 U/ml or greater (Group B), according to receiver operating characteristic (ROC) curve analysis. Tumoural status was evaluated regarding the TgAb positivity and the degree of increase of TgAb. RESULTS: Thirty-seven (13.4%) of 276 TgAb+ patients were finally diagnosed with recurrence, compared with 21 (13.5%) of 156 TgAb- patients (P = 0.987). There was a correlation between TgAb level and recurrence (P = 0.032). Recurrence was more common in Group B than Group A (27.8% and 9.9%, respectively, P = 0.001). Recurrence was found in 37.5% of 24 TgAb+/Tg- patients who showed a gradually increasing tendency in serial measurements of TgAb. Sixteen cervical foci (21.1%) missed on neck USG and 17 lesions (22.4%) located outside the neck were additionally detected with PET/CT in TgAb+ patients. CONCLUSIONS: TgAb plays a complementary role to Tg in the detection of recurrence of DTC. Tumour recurrence was more frequent in patients with elevated TgAb level over 140 U/ml or a trend toward increasing levels. PET/CT could provide additional information to I-WBS and neck USG in detecting tumour recurrence in patients with elevated TgAb.

Incidental pituitary uptake on whole-body 18F-FDG PET/CT: a multicentre study.

PURPOSE: The purpose of this study was to determine the incidence of incidental pituitary uptake on whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and to investigate its clinical significance. METHODS: The files of 40,967 patients who underwent whole-body FDG PET/CT were retrospectively reviewed. Quantification of pituitary metabolic activity was obtained by using the maximum standardized uptake value (SUVmax). Hormone assays and pituitary MRIs were performed to assess pituitary lesions. RESULTS: Focally increased pituitary FDG uptake on PET/CT was found in 30 of 40,967 patients, accounting for an incidence of 0.073%. The mean SUVmax of 30 patients was 8.9±6.6 (range: 3.2-32.6). Histological diagnosis was obtained in three patients and included two growth hormone-secreting adenomas and one non-functioning adenoma. Hormone assays were performed on serum samples from 11 patients, 2 of whom were shown to have hypersecretion of pituitary hormone. MRI was performed on 19 patients. Abnormal MRI findings suggesting a pituitary mass were found in 18 of 19 cases (94.7%). The mean SUV(max) calculated without correction for partial volume effect for macroadenomas was significantly higher than the SUVmax for microadenomas (11.5±8.4 vs 4.8±1.3; p<0.05). There were no cases diagnosed with metastasis to the pituitary gland during clinical follow-up. CONCLUSION: Incidental pituitary FDG uptake was a very rare finding. Cases with incidental pituitary FDG uptake were diagnosed primarily with clinically non-functioning adenomas, and there were also a few functioning adenomas. Further evaluations, including hormone assays and pituitary MRI, are warranted when pituitary uptake is found on FDG PET/CT.

Paradoxical exacerbation of preexisting Graves' disease induced by insufficient radioiodine treatment: a report of five patients.

OBJECTIVE: This study reports on early and paradoxical aggravation of hyperthyroidism, which needs long-term treatment, in patients with Graves' disease after radioactive iodine (RAI) treatment. METHODS: Five patients (0.4%) out of 1333 consecutive patients with Graves' disease who underwent RAI treatment by using an empirical fixed dose of I between January 2000 and March 2006 revisited the emergency center because of early and markedly aggravated thyrotoxic manifestations, which seemed to differ from those for radiation-induced thyroiditis. The clinical features, changes in the laboratory, and scintigraphic findings before and after RAI treatment, and long-term follow-up of these patients were reviewed retrospectively. RESULTS: The mean interval between the RAI treatment and paradoxical exacerbation of hyperthyroidism was 47.8 days (range: 28-69 days). In all five patients, the serum levels of thyroid hormones were markedly increased compared with those before the RAI treatment. The patients also exhibited an increased uptake of radioiodine or technetium-99m pertechnetate on the scintigraphy after RAI treatment. The serum levels of thyrotropin receptor antibodies were increased compared with those before the RAI treatment. Immediate and long-term treatments with antithyroid medications or second dose of RAI treatment were required in all the patients to control persistent hyperthyroidism. CONCLUSION: The early and paradoxical exacerbation of preexisting Graves' disease, as distinct from radiation-induced thyroiditis, can occur after insufficient dose of RAI treatment for Graves' disease.

Enhanced scintigraphic visualization of thyroglossal duct remnant during hypothyroidism after total thyroidectomy: prevalence and clinical implication in patients with differentiated thyroid cancer.

OBJECTIVE: The exact prevalence and clinical significance of ectopic thyroid or thyroglossal duct remnant (TGDR) in the general population have not yet been fully determined despite numerous case reports. This study was prepared to assess the prevalence of TGDR in asymptomatic subjects during hypothyroidism after a total thyroidectomy for differentiated thyroid cancer (DTC) and to clarify the clinical implication. DESIGN: Tc-99m pertechnetate scintigraphy (Tc-scan) of the head and neck before radioiodine ablation therapy and whole-body and pinhole I-131 scintigraphy (I-scan) after ablation therapy were reviewed for 131 consecutive DTC patients with hypothyroidism after a total thyroidectomy. MAIN OUTCOME: Forty-four among the 131 patients (33.6%) revealed an unexpected linear or focal radioactivity at the anterior midline of the neck, suggesting the presence of TGDR. The Tc-scan and pinhole I-scan were concordant in all cases of abnormal midline neck uptake, although the planar I-scan failed to delineate TGDR due to prominent photon scattering in most cases. Preoperative enhanced neck computed tomography scan was performed in 49 patients and showed no evidence of thyroid glandular tissue separated from thyroid gland in midline of the anterior neck except 1 case. The success rate after radioiodine ablation did not differ significantly between the positive and negative TGDR patients. CONCLUSIONS: TGDR can be frequently observed in scintigraphy of hypothyroid subjects after a thyroidectomy, even when clinically unexpected. Therefore, care should be taken not to confuse the tracer uptake by TGDR with metastatic foci in I- and Tc-scans of patients with hypothyroidism after a thyroidectomy for DTC.

Difference in F-18 FDG Uptake After Esophagogastroduodenoscopy and Colonoscopy in Healthy Sedated Subjects.

PURPOSE: We aimed to evaluate the difference in fluorodeoxyglucose (FDG) uptake in sedated healthy subjects after they underwent esophagogastroduodenoscopy (EGD) and colonoscopy procedures. METHODS: The endoscopy group (n = 29) included healthy subjects who underwent screening via F-18 FDG positron emission tomography/computed tomography (PET/CT) after an EGD and/or colonoscopy under sedation on the same day. The control group (n = 35) included healthy subjects who underwent screening via PET/CT only. FDG uptake in the tongue, uvula, epiglottis, vocal cords, esophagus, stomach, duodenum, liver, cecum, colon, anus, and muscle were compared between the two groups. RESULTS: Maximum standardized uptake value (SUVmax) in the tongue, pharynx, larynx, and esophagus did not significantly differ between the endoscopy and control groups. In contrast, mean SUVmax in the whole stomach was 18 % higher in the endoscopy group than in the control group (SUVmax: 2.96 vs. 2.51, P = 0.010). In the lower gastrointestinal track, SUVmax from the cecum to the rectum was not significantly different between the two groups, whereas SUVmax in the anus was 20 % higher in the endoscopy group than in the control group (SUVmax: 4.21 vs. 3.50, P = 0.002). SUVmax in the liver and muscle was not significantly different between the two groups. Mean volume of the stomach and mean cross section of the colon was significantly higher in the endoscopy group than in the control group (stomach: 313.28 cm3 vs. 209.93 cm3, P < 0.001, colon: 8.82 cm2 vs. 5.98 cm2, P = 0.001). CONCLUSIONS: EGD and colonoscopy under sedation does not lead to significant differences in SUVmax in most parts of the body. Only gastric FDG uptake in the EGD subjects and anal FDG uptake in the colonoscopy subjects was higher than uptake in those regions in the control subjects.

Extra-thoracic tumor burden but not thoracic tumor burden on (18)F-FDG PET/CT is an independent prognostic biomarker for extensive-disease small cell lung cancer.

PURPOSE: The aim of this study was to evaluate the relationship and difference in prognostic significance between whole-body tumor burden, thoracic tumor burden, and extra-thoracic tumor burden on (18)F-FDG PET/CT for patients with extensive-disease small cell lung cancer (ED-SCLC). MATERIALS AND METHODS: We performed a retrospective, two-center analysis for patients with ED-SCLC who underwent pretreatment (18)F-FDG PET/CT. Metabolic tumor burden was estimated using whole-body metabolic tumor volume (MTV(WB)), thoracic metabolic tumor volume (MTV(TRX)), extra-thoracic metabolic tumor volume (MTV(EXT)), and the number of extra-thoracic tumor foci. Uni- and multivariate analyses were performed using various clinical factors and the metabolic indices. RESULTS: A total of 91 patients were eligible for this study. MTV(WB) showed stronger correlation with MTV(EXT) than MTV(TRX) (r(2) = 0.804 vs. 0.132, p < 0.001, both), whereas no correlation was observed between MTV(EXT) and MTV(TRX) (r(2) = 0.007, p = 0.428). Patients with smaller MTV(WB), MTV(EXT), and extra-thoracic tumor foci showed longer survival than patients with larger MTV(WB), MTV(EXT), and extra-thoracic tumor foci, respectively, whereas the survival difference between patients with smaller MTV(TRX) and those with larger MTV(TRX) was not significant. Results of uni- and multivariate analyses showed that ECOG performance status (HR = 2.31, p = 0.015), initial chemotherapy cycles (HR = 0.24, p < 0.001), and the number of extra-thoracic tumor foci (HR = 2.75, p < 0.001) were independent prognostic factors for overall survival, and initial chemotherapy cycles (HR = 0.25, p < 0.001), and MTV(EXT) (HR = 2.04, p = 0.013) were independent prognostic factors for progression-free survival. CONCLUSION: These data provide evidence indicating that extra-thoracic tumor burden but not thoracic tumor burden is an independent prognostic biomarker for ED-SCLC, and support further exploration of novel treatment strategies targeting extra-thoracic tumor burden in order to improve the clinical outcomes of patients with ED-SCLC.

A stepwise approach using metabolic volume and SUVmax to differentiate malignancy and dysplasia from benign colonic uptakes on 18F-FDG PET/CT.

PURPOSE: The purpose of this study was to suggest a new diagnostic strategy using metabolic volume (MV) and maximum standardized uptake value (SUVmax) to differentiate malignancy and dysplasia from benign colonic 2-deoxy-2-18F-fluoro-D-glucose (FDG) uptakes. MATERIALS AND METHODS: From records of 21,317 consecutive FDG positron emission tomography/computed tomography (PET/CT) scans at 2 centers, 102 focal colonic lesions in 99 patients investigated by colonoscopy and histopathologic examination were eligible for this retrospective study. SUVmax and MV were compared according to colonoscopic and histopathologic results. Firstly, dysplasia was separated from malignancy and benign lesions. Secondly, malignancy and benign lesions were separated from each other. The better parameters of each step were determined, and a diagnostic strategy was developed from their combination. RESULTS: A total of 102 incidental colonic FDG uptakes were revealed as 32 malignancies, 43 dysplasias, and 27 benign lesions. MV better differentiated dysplasia from malignancy and benign lesions (cutoff value, ≤3.14 cm3; area under the receiver-operating characteristic curve [AUC] = 0.947), and SUVmax better differentiated malignancy from benign lesions (cutoff value, >9.1; AUC = 0.934). Overall, the stepwise algorithm using MV and SUVmax (AUC = 0.886) was superior to single measurements of SUVmax (AUC = 0.750) and MV (AUC = 0.714) for differentiating malignancy and dysplasia from benign lesions; sensitivity: 92%, specificity: 85%, accuracy: 90%, positive predictive value: 94%, negative predictive value: 79%. CONCLUSIONS: The stepwise approach using MV and SUVmax was able to differentiate malignancy and dysplasia from benign colonic FDG uptakes on PET/CT. Colonic FDG uptake with MV ≤3.14 cm3 had a high probability of dysplasia. MV >3.14 cm3 and SUVmax >9.1 indicated malignancy, whereas MV >3.14 cm3 and SUVmax ≤9.1 indicated benign lesions.

Pulmonary amyloidosis mimicking multiple metastatic lesions on F-18 FDG PET/CT.

We report a case of amyloid pulmonary nodules with positive FDG uptake that mimic multiple lung metastases. A 54-year-old female patient was referred for the evaluation of multiple lung nodules. A PET/CT scan revealed mild FDG uptake in various sized pulmonary nodules. Resected nodules contained amorphous eosinophilic proteineous material with focal calcification, consistent with amyloidosis. Pulmonary amyloidosis should be added to the differential diagnosis for cases of multiple pulmonary nodules that show positive FDG uptake.

Trafficking macrophage migration using reporter gene imaging with human sodium iodide symporter in animal models of inflammation.

UNLABELLED: The aim of this study was to investigate the feasibility of nuclear molecular imaging using the human sodium iodide symporter (hNIS) as a reporter gene to monitor macrophage migration toward the inflammatory foci. METHODS: A stable macrophage cell line coexpressing hNIS and green fluorescent protein (GFP) genes (RAW264.7/hNIS-GFP and R(NIS) cell) was established from an immortalized macrophage cell line (RAW264.7 cells). (125)I uptake was determined (for hNIS protein functional activity), and flow cytometry analysis (to examine GFP gene expression), a cell proliferation assay, a cytokine assay, and a phagocytic activity assay were performed. (99m)Tc-pertechnetate images were acquired at 1 d after subcutaneous inoculation of R(NIS) cells in nude mice. Chemical inflammation was induced for in vivo imaging in the thigh of nude mice by turpentine oil injection. Small-animal PET with (18)F-FDG and (124)I was performed with an intravenous administration of RAW264.7 or R(NIS) cells in inflammation-induced animals. RESULTS: The expression of hNIS and GFP genes was confirmed in R(NIS) cells by flow cytometry and immunofluorescent staining. (125)I uptake was about 67 times higher in R(NIS) cells than in RAW264.7 cells. No significant difference was observed in cell proliferation, cytokine production, and phagocytic activity between RAW264.7 and R(NIS) cells. (99m)Tc-pertechnetate imaging revealed increased tracer uptake at the inoculation site. PET with (124)I demonstrated a donut-shaped uptake, correlating with uptake shown by the (18)F-FDG PET images, at the inflammation site of mice administered R(NIS) cells. (124)I uptake (percentage injected dose per gram) was about 2.12 times higher at the inflammation site in the R(NIS) mice than in RAW264.7 mice. By immunohistochemistry, the migration of macrophages was further confirmed by positive staining for GFP and hNIS at the inflammation site of R(NIS) mice. CONCLUSION: These data support the feasibility of hNIS reporter gene imaging to monitor the macrophage migration toward an inflammatory lesion. Macrophages expressing hNIS may provide a new strategy to investigate the cellular behavior seen with inflammatory response in a preclinical model.

Dose-dependent frontal hypometabolism on FDG-PET in methamphetamine abusers.

OBJECTIVE: Although a lot of evidence from neuropsychological and neuroimaging studies supports the view that patients with substance dependence have abnormalities in the prefrontal cortex, functional deficits in the prefrontal cortex have not been fully investigated in methamphetamine (MA) dependent patients. This study was prepared to examine whether MA abusers have cerebral metabolic abnormalities and executive dysfunction. METHOD: Twenty-four abstinent MA dependent patients and 21 age-matched control subjects underwent resting brain FDG-PET and completed computerized versions of the Wisconsin card sorting test (WCST). Resting brain PET images were obtained 30min after an intravenous injection of 370MBq of (18)F-FDG. Significant differences in glucose metabolism were estimated for every voxel using t-statistics on SPM2 implemented in Matlab. RESULTS: Resting brain FDG-PET revealed significant hypometabolism in the left inferior frontal white matter (Talairach coordinates (x, y, z): -34, 7, 31) in MA dependent patients compared to the control subjects (corrected p=0.001, peak Z=5.37, voxel number 201). The nearest gray matter region was the left inferior frontal cortex (Brodmann area 9). There were negative correlations between the relative regional cerebral metabolism for glucose (rCMRglc) in the left inferior frontal white matter and the total cumulative dose of MA (r=-0.57, p<0.01). MA dependent patients completed significantly fewer categories (3.8+/-2.2) and made more perseveration errors (21.3+/-11.8) and total errors (43.5+/-19.5) on the WCST when compared to the control subjects (p<0.01). CONCLUSIONS: These data suggest that MA dependent patients have dose-dependent frontal hypometabolism and frontal executive dysfunction.