[en] The purpose of this prospective study was to evaluate yttrium-90 glass microsphere treatment of unresectable liver metastases by fluorine-18 fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET), and to compare the effectiveness of [¹⁸F]FDG PET for this purpose with that of computed tomography (CT) or magnetic resonance imaging (MRI) and determination of the serum carcinoembryonic antigen (CEA) level. Thirteen hepatic lobes from eight consecutive patients with colorectal cancer referred for ⁹⁰Y-glass microsphere treatment of unresectable liver metastases who underwent both baseline (pretreatment) and 3-month posttreatment PET were studied. All patients also had correlative pre- and posttreatment CT or MRI for evaluation of the anatomic response and serum CEA determination for assessment of the total tumor load, as well as pretreatment hepatic intra-arterial technetium-99m macroaggregated albumin scan for lung shunting evaluation and hepatic arteriography for assessment of vascular anatomy and treatment. ⁹⁰Y-glass microspheres were infused via an intra-arterial catheter under low pressure. Dedicated whole-body PET scans were analyzed visually and compared by lesion and by lobe with CT or MRI. A metabolic response after ⁹⁰Y treatment to single or both hepatic lobes, assessed by PET, was present in a significantly higher proportion of the lobes than was an anatomic response, evaluated by CT or MRI (12 vs 2 lobes respectively, P<0.0002). Posttreatment PET showed no, stable, progressive, and new extrahepatic metastases in two, three, one, and two patients respectively. Following treatment, serum CEA decreased significantly, correlating with PET but not with CT or MRI. Thus, the study demonstrated a significant difference between the metabolic and the anatomic response after ⁹⁰Y-glass microsphere treatment for unresectable liver metastases in colorectal cancer. PET appears to be an accurate indicator of treatment response. (orig.)

[en] Full text: Objectives: To evaluate the incremental diagnostic value of integrated interpretation of PET/CT in evaluating solitary pulmonary nodules for malignancy. Methods: A total of 117 patients (67 male and 50 female, mean age±SD: 61.7±13.6 years, range: 31-86 years) with indeterminate solitary pulmonary nodules and without previous history of malignancy were analyzed. The PET/CT was performed I hour after a 370 MBq 18F-FDG intravenous injection using an integrated PET/CT scanner (Siemens Biograph BGO duo). Patients fasted 6 hour prior the imaging. PET was interpreted alone or combined with CT and was graded with the described 5-point scale. Malignant diagnosis was based on histological findings or a clinical and radiological follow-up of at least 24 months. Diagnostic performance of PET alone and integrated criteria were performed using a discriminant analysis. Results: PET alone classified correctly 85% and the integrated criteria increased the correct classification to 89% yet comparable sensitivity and specificity of 88% and 89% respectively. False positive PET results were mainly from granulomatous disorders. Four out of 8 PET indeterminate cases by PET alone were resolved (50%) when combined with the CT interpretation. Conclusions: While additional gain of integrated PET/CT from the CT part was limited, PET and CT are synergistic and significantly increment of diagnostic value in PET indeterminate cases.

[en] The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H₂O cerebral uptake in normal subjects. Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H₂O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the gloabl maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences. Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion. The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers

[en] To evaluate the use of unbiased computer-assisted lateralization of temporal lobe epilepsy (TLE) by z-score parametric PET imaging (ZPET). 38 patients with histologically proven unilateral TLE due to pure hippocampal sclerosis, referred for pre-surgical PET evaluation of intractable seizure over a 5-year period, were included. The F-18 FDG images were oriented along temporal long axis and then transformed into ZPET images on a voxel by voxel basis. Multiple regions of interests (21 in total) were placed on cortical, subcortical and cerebellar structures on twenty-eight out of 38 patients with totally seizure-free (class I) outcome. Paired t-tests with Bonferroni correction were used to determine the location of the most asymmetric regions as variables for subsequent discriminant analysis of the entire group of the patients. The computer program identified the anterior half of the temporal lobe (p < 0.0005) and thalami (p = 0.021) as the most asymmetric regions in TLE patients with Class I outcome. Discriminant analysis using z-scores from a total of 8 ROIs (in 4 pairs) on these structures correctly lateralized thirty-seven out of 38 (97%) patients (sensitivity = 94%; specificity = 100%). The only false localization came from a patient with equivocal z-scores on the temporal lobes and this patient turned out to have poor outcome. The computer-assisted lateralization of TLE using ZPET provides an accurate, fast and objective way of seizure evaluation

[en] Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

[en] The aims were to determine if the maximum standardized uptake value (SUV_max) of the primary tumor as determined by preoperative ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) positron emission tomography (PET) is an independent predictor of overall survival and to assess its prognostic value after stratification according to pathological staging. A retrospective clinicopathologic review of 363 patients who had a preoperative ¹⁸F-FDG PET done before undergoing attempted curative resection for early-stage (I and II) non-small cell lung cancer (NSCLC) was performed. Patients who had received any adjuvant or neoadjuvant chemotherapy or radiation therapy were excluded. The primary outcome measure was duration of overall survival. Receiver-operating characteristic (ROC) curves were plotted to find out the optimal cutoff values of SUV_max yielding the maximal sensitivity plus specificity for predicting the overall survival. Survival curves stratified by median SUV_max and optimal cutoff SUV_max were estimated by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUV_max's independency of other prognostic factors for the prediction of overall survival. The median duration of follow-up was 981 days (2.7 years). The median SUV_max was 5.9 for all subjects, 4.5 for stage IA, 8.4 for stage IB, and 10.9 for stage IIB. The optimal cutoff SUV_max was 8.2 for all subjects. No optimal cutoff could be established for specific stages. In univariate analyses, each doubling of SUV_max [i.e., each log (base 2) unit increase in SUV_max] was associated with a 1.28-fold [95% confidence interval (CI): 1.03-1.59, p = 0.029] increase in hazard of death. Univariate analyses did not show any significant difference in survival by SUV_max when data were stratified according to pathological stage (p = 0.119, p = 0.818, and p = 0.882 for stages IA, IB, and IIB, respectively). Multivariate analyses demonstrated that SUV_max was not an independent predictor of overall survival (p > 0.05). Each doubling of SUV_max as determined by preoperative PET is associated with a 1.28-fold increase in hazard of death in early-stage (I and II) NSCLC. Preoperative SUV_max is not an independent predictor of overall survival. (orig.)

[en] Purpose: To investigate the metabolic information provided by ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during the early response of head-and-neck squamous cell carcinoma (HNSCC) xenografts to radiotherapy (RT). Methods and Materials: Low-passage HNSCC cells (UT14) were injected into the rear flanks of female nu/nu mice to generate xenografts. After tumors grew to 400–500 mm³, they were treated with either 15 Gy in one fraction (n = 18) or sham RT (n = 12). At various time points after treatment, tumors were assessed with 2-h dynamic FDG-PET and immediately harvested for direct histological correlation. Different analytical parameters were used to process the dynamic PET data: kinetic index (Ki), standard uptake value (SUV), sensitivity factor (SF), and retention index (RI). Tumor growth was assessed using the specific growth rate (SGR) and correlated with PET parameters using the Pearson correlation coefficient (r). Receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to test PET parameters for their ability to predict for radiation necrosis and radiation change. Results: Tumor growth was arrested for the first 20 days after RT and recovered thereafter. Histologically, radiation change was observed in the peripheral regions of tumors between days 7 and 23 after RT, and radiation necrosis were observed in the central regions of tumors between days 7 and 40. Ki provided the best correlation with SGR (r = 0.51) and was the optimal parameter to predict for early radiation necrosis (AUC = 0.804, p = 0.07). SUV_30min was the strongest predictor for late radiation necrosis (AUC = 0.959, p = 0.004). Both RI_30–60min and SF_12–70min were very accurate in predicting for radiation change (AUC = 0.891 and 0.875, p = 0.009 and 0.01, respectively). Conclusions: Dynamic FDG-PET analysis (such as Ki or SF) may provide informative assessment of early radiation necrosis or radiation change of HNSCC xenografts after RT.

[en] Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

[en] Purpose: To address glucose sensitivity in lung cancers before and after radiation treatment (Tx). Methods and Materials: Twelve patients were each studied with two pre-Tx positron emission tomography (PET) scans and 3 patients each with one post-Tx PET scan, with glucose concentration [Glc] and maximum standard uptake value (SUV) recorded. The pre-Tx glucose sensitivity, g from SUV₁/SUV₂ = {[Glc]₁/[Glc]₂}^g and Tx index, τ from SUV_post-Tx/SUV_pre-Tx = {[Glc]_post-Tx/[Glc]_pre-Tx}^τ was calculated by linear regression. Pre-Tx SUVs were corrected to post-Tx Glc with g (SUV'_pre-Tx) for a pure Tx effect, R ln(SUV_post-Tx/SUV'_pre-Tx). Results: There were no significant differences in SUV but [Glc] were different (96.4 ± 10.9 vs. 88.3 ± 10.5, p = 0.015) between two pre-Tx PET scans. Linear regression yielded g -0.79 and τ = -1.78 to -2.41 (p < 0.0005 in all). The %ΔSUV after Tx for 3 patients without vs. with g correction were different by -12%, 0%, and + 7%, suggesting varying effects from glucose. R values were also different and mean R (-0.81 ± 0.38) was significantly different from zero (p = 0.03), consistent with successful Tx as confirmed by clinico-radiologic follow-up. Conclusions: The extra dimension of glucose sensitivity, g besides SUV incorporated in the combined Tx-derived τ may be a useful global Tx evaluation index even with differing [Glc]

[en] Objective: This study acquired fluorine-18-deoxyglucose (FDG) kinetic parameters prior and subsequent to cisplatin chemotherapy so as to define the optimal parameters for early prediction of chemotherapy response. Methods: A total of 12 non-tumor-bearing rabbits were used to obtain noninvasive input function, five VX2 tumor-bearing rabbits were used for validation and 32 tumor-bearing rabbits underwent 4 mg kg^-1 cisplatin chemotherapy. Dynamic FDG PET/CT was performed at pretherapy, Day 0, Day 1, Day 7 and Day 14 after cisplatin administration. With the application of a three-compartment model, influx index (Ki), k1, k2, k3 and k4 were noninvasively obtained. Results: Sensitive (SG) and insensitive groups (ISG) were defined based on their volume on Day 7. k1, Ki, SUVmean, and SUVmax showed significant decreases in SG vs. ISG at Day 0 (P<.076-0.0001). k1 demonstrated sustained (up to Day 7) differences (P<.028-0.0072), and k2, k3 and k4 showed no significant differences at any time point (P>.05). Soon after cisplatin administration, GLUT-1 expression was greatly decreased in SG vs. ISG. Conclusions: The parameters of SUVmax, SUVmean, Ki and k1 were valuable for the early prediction of chemotherapy response. k1 had a wider observation window compared to SUVmean, SUVmax and Ki, and k1 also reflected the changes in GLUT-1 expression.