Jae Seung Kim

Prediction of prognosis using standardized uptake value of 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography for nasopharyngeal carcinomas

PURPOSE To evaluate the prognostic significance of 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography ([(18)F]FDG-PET) at diagnosis by calculating maximal standard uptake values (SUV(max)) in patients with non-disseminated nasopharyngeal carcinoma (NPC) receiving concurrent chemo-radiotherapy (CCRT). MATERIALS AND METHODS [(18)F]FDG-PET was performed in 41 patients with non-disseminated NPC scheduled to undergo platinum-based CCRT. [(18)F]FDG uptake by primary tumors and neck nodes was measured with the SUV(max). RESULTS Complete response occurred in all 41 patients. The ten patients who presented with any component of treatment failure had a significantly higher SUV(max) than the remaining patients. The median SUV(max) of all patients was 6.48 (range: 2.31-26.07). Patients having tumors with high [(18)F]FDG uptake (median or greater) had a significantly lower 3-year disease free survival (DFS) rate than patients with lower tumor [(18)F]FDG uptake (less than median) (51% vs 91%, P=0.0070). Patients with an SUV(max) below 8 had a higher DFS than patients with an SUV(max) of 8 or greater. CONCLUSION [(18)F]FDG uptake, as measured by the SUV(max), may predict DFS in CCRT-treated NPC. High [(18)F]FDG uptake may be useful for identifying patients requiring more aggressive treatment.

Utility of combined 18F-fluorodeoxyglucose-positron emission tomography and computed tomography in patients with cervical metastases from unknown primary tumors

(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful screening method for primary tumor detection, accurate nodal staging, and distant metastases in patients with CUPs.

Prognostic Value of Preoperative Metabolic Tumor Volume and Total Lesion Glycolysis Measured by 18F-FDG PET/CT in Salivary Gland Carcinomas

Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are emerging prognostic biomarkers in various human cancers. This study examined the prognostic value of these metabolic tumor parameters measured by pretreatment 18F-FDG PET/CT in patients with salivary gland carcinomas. Methods: Forty-nine patients with intermediate- or high-grade salivary gland carcinomas who underwent definitive surgery with or without radiotherapy or chemoradiotherapy were evaluated preoperatively by 18F-FDG PET/CT. Maximum standardized uptake values (SUVmax), MTV, and TLG were measured for each patient. Univariate and multivariate analyses were used to identify clinicopathologic and imaging variables associated with progression-free survival (PFS) and overall survival (OS). Univariate analyses included the following variables: age, sex, pT and pN classifications, overall pTNM stage, histologic grade, resection margin, tumor lymphovascular invasion and perineural invasion, postoperative adjuvant therapy, gross total volume, SUVmax, MTV, and TLG. Results: The 3-y PFS and OS rates for all study patients were 66.9% and 81.6%, respectively. The median SUVmax, MTV, and TLG were 5.1 (range, 1.7–21.5), 16.2 mL (1.0–115.1 mL), and 24.4 g (2.1–224.4 g), respectively. Univariate analyses showed that there were significant correlations between pT classification, pN classification, MTV, and TLG and both PFS and OS (P < 0.05). However, SUVmax was not associated with either PFS (P = 0.111) or OS (P = 0.316). Multivariate analyses revealed that MTV (P = 0.011; hazard ratio, 11.50; 95% confidence interval, 1.45–91.01) and TLG (P = 0.038; hazard ratio, 3.55; 95% confidence interval, 1.07–11.76) were independent variables for PFS. Conclusion: Pretreatment values of MTV and TLG are independent prognostic factors in patients with intermediate or high-grade salivary gland carcinomas.

Combined [18F]fluorodeoxyglucose positron emission tomography and computed tomography for detecting contralateral neck metastases in patients with head and neck squamous cell carcinoma

We evaluated the clinical utility of combined [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT), as well as CT and magnetic resonance imaging (MRI) in identifying nodal metastases in the contralateral neck in patients with head and neck squamous cell carcinoma (HNSCC). A total of 114 patients were preoperatively evaluated with PET/CT and CT/MRI. Histopathologic analysis from bilateral neck dissection tissues was used as the gold standard in assessing these imaging techniques. Of the 114 patients, 63 (55%) had neck metastases and 26 (23%) had contralateral neck metastases. On a per-level basis, FDG PET/CT was significantly more sensitive and accurate than CT/MRI in the ipsilateral (88% vs. 70%, P<0.01 and 93% vs. 89%, P<0.01, respectively) and contralateral (52% vs. 36%, P<0.01 and 91% vs. 90%, P=0.039, respectively) neck. PET/CT and CT/MRI were less sensitive in detecting contralateral than ipsilateral neck metastases due to the lower incidence of metastases and smaller nodes on the contralateral side. Combined PET/CT is superior to CT/MRI in detecting metastatic neck nodes in HNSCC patients. However, PET/CT may not abrogate the need for contralateral neck surgery or radiotherapy in these patients.

Role of FDG-PET as a biological marker for predicting the hypoxic status of tongue cancer.

To determine whether 2‐[18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) could serve as a useful technique predicting tumor hypoxia and prognosis in tongue cancer, we assessed the relationship between FDG uptake and the levels of hypoxia‐related markers.

(4S)-4-(3-18F-Fluoropropyl)-l-Glutamate for Imaging of xC¯ Transporter Activity in Hepatocellular Carcinoma Using PET: Preclinical and Exploratory Clinical Studies

(4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG, or BAY 94-9392) is a new tracer to assess system xC¯ transporter activity with PET. The aim of this study was to explore the tumor detection rate of 18F-FSPG, compared with that of 18F-FDG, in patients with hepatocellular carcinoma (HCC). Methods: Preclinically, in vivo HCC models of orthotopically implanted Huh7 and MH3924a cancer cells were studied with 18F-FSPG in Naval Medical Research Institute nude mice (n = 3) and August-Copenhagen Irish rats (n = 4), respectively. Clinically, 5 patients with HCC who had hyper- or isometabolic lesions on 18F-FDG PET were enrolled for evaluation of the tracer. Dynamic whole-body PET images with 18F-FSPG were acquired for up to 120 min after injection of approximately 300 MBq of 18F-FSPG. Immunohistochemical expression levels of the xCT subunit of the system xC¯ and CD44 of HCC were studied in 4 patients with HCC. Results: Strong tumor uptake and low background from nontarget tissue allowed excellent tumor visualization in animal models with orthotopically implanted liver tumors. 18F-FSPG PET procedures were well tolerated in all patients. 18F-FSPG PET and 18F-FDG detected lesions in 5 of 5 and 3 of 5 patients, respectively. The maximal standardized uptake values (SUV) were comparable (18F-FSPG, 4.7 ± 3.2; 18F-FDG, 6.1 ± 2.9). The ratios of maximal SUV of the tumor to mean SUV of normal liver were also comparable (18F-FSPG, 3.6 ± 2.2; 18F-FDG, 2.7 ± 1.3), but the mean SUV of normal liver of 18F-FSPG was significantly lower than that of 18F-FDG (P < 0.05). Two patients with HCC who showed both xCT and CD44 expression had moderate or intense accumulation of 18F-FSPG, but the remaining 2 patients with negative CD44 expression showed mild uptake. Conclusion: 18F-FSPG was successfully translated from preclinical evaluation into patients with HCC. 18F-FSPG may be a promising tumor PET agent with a high cancer detection rate in patients with HCC.

18F-FDG PET/CT for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma.

Distant metastases (DMs) increase in patients with recurrent head and neck squamous cell carcinoma (HNSCC). We evaluated the ability of fluorine 18‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) to detect DMs in these patients.

Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy

Purpose:  The metabolic and biochemical changes that occur during epileptogenesis remain to be determined. 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) and proton magnetic resonance spectroscopy (1H MRS) are noninvasive techniques that provide indirect information on ongoing pathologic changes. We, therefore, utilized these methods to assess changes in glucose metabolism and metabolites in the rat lithium‐pilocarpine model of epilepsy as markers of epileptogenesis from baseline to chronic spontaneous recurrent seizures (SRS).

Relationship between hypometabolic patterns and ictal scalp EEG patterns in patients with unilateral hippocampal sclerosis: An FDG―PET study

This study was to explore the relationship between scalp ictal EEG patterns and interictal hypometabolic patterns in hippocampal sclerosis-associated mesial temporal lobe epilepsy (HS-MTLE) and determine the clinical significance of interictal hypometabolic patterns. Twenty-five patients were classified into 2 groups based on initial ictal discharge (IID) frequency on scalp EEG: (a) those with a sustained regular 5- to 9-Hz rhythm with a restricted temporal or subtemporal distribution (group 1, N=9); and (b) those with an irregular 2- to 5-Hz rhythm with a widespread distribution (group 2, N=16). Using statistical parametric mapping, the PET results of each group were compared with age- and sex-matched controls to identify regions of significant hypometabolism, and the clinical characteristics were compared. Group 1 showed focal hypometabolism confined to the ipsilateral temporal lobe, whereas group 2 showed widespread hypometabolism in the ipsilateral temporal lobe, insular cortex and anterior part of the putamen. The two groups showed no significant differences in clinical characteristics. Among semiologic features, dystonic limb posturing was more frequently observed in group 2 (p=0.03). In summary, scalp EEG IID patterns in HS-MTLE can be important in determining hypometabolic patterns on interictal PET. Differences in hypometabolic patterns may reflect preferential pathways of ictal propagation rather than intrinsic epileptogenic regions.

Correlation of interictal spike-wave with thalamic glucose metabolism in juvenile myoclonic epilepsy.

The purpose of this study is to define metabolic correlates of generalized spike-wave discharges in juvenile myoclonic epilepsy. We investigated the alterations in glucose metabolism and possible correlations between the interictal epileptiform discharges and regional metabolism in patients with juvenile myoclonic epilepsy using a combined positron emission tomography/electroencephalography method. We found that the thalamic metabolism is slightly increased interictally in the patient group compared with controls. We also observed significant positive correlations between the amount of spike-wave activity and thalamic metabolism. Our results provide evidence that the thalamus has an important role in the generation of spontaneous generalized spike-wave discharges in juvenile myoclonic epilepsy.