Change of Therapeutic Response Classification According to Recombinant Human Thyrotropin‑Stimulated Thyroglobulin Measured at Different Time Points in Papillary Thyroid Carcinoma / 대한핵의학회잡지

Purpose@#We investigated whether response classification after total thyroidectomy and radioactive iodine (RAI) therapy could be affected by serum levels of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) measured at different time points in a follow-up of patients with papillary thyroid carcinoma (PTC). @*Methods@#A total of 147 PTC patients underwent serum Tg measurement for response assessment 6 to 24 months after the first RAI therapy. Serum Tg levels were measured at 24 h (D1Tg) and 48–72 h (D2-3Tg) after the 2nd injection of rhTSH. Responses were classified into three categories based on serum Tg corresponding to the excellent response (ER-Tg), indeterminate response (IR-Tg), and biochemical incomplete response (BIR-Tg). The distribution pattern of response classification based on serum Tg at different time points (D1Tg vs. D2-3Tg) was compared. @*Results@#Serum D2-3Tg level was higher than D1Tg level (0.339 ng/mL vs. 0.239 ng/mL, P < 0.001). The distribution of response categories was not significantly different between D1Tg-based and D2-3Tg-based classification. However, 8 of 103 (7.8%) patients and 3 of 40 (7.5%) patients initially categorized as ER-Tg and IR-Tg based on D1Tg, respectively, were reclassified to IR-Tg and BIR-Tg based on D2-3Tg, respectively. The optimal cutoff values of D1Tg for the change of response categories were 0.557 ng/mL (from ER-Tg to IR-Tg) and 6.845 ng/mL (from IR-Tg to BIR-Tg). @*Conclusion@#D1Tg measurement was sufficient to assess the therapeutic response in most patients with low level of D1Tg. Nevertheless, D2-3Tg measurement was still necessary in the patients with D1Tg higher than a certain level as response classification based on D2-3Tg could change.

Recent Progress in the Molecular Imaging of Tumor-Treating Bacteria / 대한핵의학회잡지

Bacterial cancer therapy (BCT) approaches have been extensively investigated because bacteria can show unique features of strong tropism for cancer, proliferation inside tumors, and antitumor immunity, while bacteria are also possible agents for drug delivery. Despite the rapidly increasing number of preclinical studies using BCT to overcome the limitations of conventional cancer treatments, very few BCT studies have advanced to clinical trials. In patients undergoing BCT, the precise localization and quantification of bacterial density in different body locations is important; however, most clinical trials have used subjective clinical signs and invasive sampling to confirm bacterial colonization. There is therefore a need to improve the visualization of bacterial densities using noninvasive and repetitive in vivo imaging techniques that can facilitate the clinical translation of BCT.In vivo optical imaging techniques using bioluminescence and fluorescence, which are extensively employed to image the therapeutic process of BCT in small animal research, are hard to apply to the human body because of their low penetrative power. Thus, new imaging techniques need to be developed for clinical trials. In this review, we provide an overview of the various in vivo bacteria-specific imaging techniques available for visualizing tumor-treating bacteria in BCT studies.

Clinical Impact of F-18 FDG PET-CT on Biopsy Site Selection in Patients with Suspected Bone Metastasis of Unknown Primary Site / 대한핵의학회잡지

Purpose@#We investigated the clinical role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography(PET-CT) in the identification of the primary site and the selection of the optimal biopsy site in patients with suspectedbone metastasis of unknown primary site. @*Methods@#The patients with suspected bone metastasis who underwent PET-CT for evaluation of primary site were enrolled inthis study. The primary sites were identified by the histopathologic or imaging studies and were classified according to the FDGuptake positivity of the primary site. To evaluate the guiding capability of PET-CT in biopsy site selection, we statisticallyanalyzed whether the biopsy site could be affected according to the presence of extra-skeletal FDG uptake. @*Results@#Among 74 enrolled patients, 51 patients had a metastatic bone disease. The primary site was identified in 48 of 51patients (94.1%). Forty-six patients were eligible to test the association of clinical choice of biopsy site with PET positivity ofextra-skeletal lesion. The extra-skeletal biopsies were done in 42 out of 43 patients with positive extra-skeletal uptake lesions.Bone biopsies were inevitably performed in the other three patients without extra-skeletal uptake lesions. The association cameout to be significant (Fisher’s exact test, P< 0.001). @*Conclusion@#F-18 FDG PET-CT significantly contributed not only to identify the primary site but also to suggest optimal biopsysites in patients with suspected bone metastasis.

Therapeutic Effect of Fimasartan in a Rat Model of Myocardial Infarction Evaluated by Cardiac Positron Emission Tomography with ¹⁸FFPTP / 전남의대학술지

We evaluated the efficacy of fimasartan on perfusion defects and infarction size in an animal model of myocardial infarction (MI), with echocardiography and positron emission tomography (PET) using a ¹⁸F-labeled phosphonium cation (5-[¹⁸F]-fluoropentyl-triphenylphosphonium salt, [¹⁸F]FPTP) as a mitochondrial voltage sensor for myocardial imaging. We induced MI in 33 rats by ligation of the left coronary artery, and checked their cardiac PET image using [¹⁸F]FPTP for evaluation of myocardial perfusion. Rats were grouped into 3 groups according to their administered drugs: no drug (n=11), fimasartan 3 mg/kg (n=10), and fimasartan 10 mg/kg (n=12). Each designated drug was administered for 4 weeks, and follow-up PET and histologic examinations were done. In the PET analysis, a perfusion defect size was markedly improved in fimasartan 10 mg/kg group (35.9±7.0% to 28.4±6.9%, p<0.001), whereas treatment with fimasartan 3 mg/kg induced only an insignificant reduction of perfusion defect size (35.9±7.9% to 33.9±7.3%, p=0.095). Using 2, 3, 5-triphenyltetrazolium chloride staining, infarction size was the largest in the control group (36.5±8.3%), and was insignificantly lower in the fimasartan 3 mg/kg group (31.5±6.5%, p for the difference between the control group=0.146) and was significantly lower in the fimasartan 10 mg/kg group (26.3±7.6%, p for the difference between the control group=0.011). PET imaging using a ¹⁸F-labeled mitochondrial voltage sensor, [¹⁸F]FPTP, is useful in evaluation and monitoring of myocardial perfusion states, and treatment with fimasartan decreases the infarction size in animal MI model.

Response Prediction of Altered Thyroglobulin Levels After Radioactive Iodine Therapy Aided by Recombinant Human Thyrotropin in Patients with Differentiated Thyroid Cancer / 대한핵의학회잡지

PURPOSE@#Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.@*METHODS@#We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.@*RESULTS@#At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).@*CONCLUSIONS@#Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

Response Prediction of Altered Thyroglobulin Levels After Radioactive Iodine Therapy Aided by Recombinant Human Thyrotropin in Patients with Differentiated Thyroid Cancer / 대한핵의학회잡지

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).CONCLUSIONS: Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

Salmonella-Mediated Cancer Therapy: Roles and Potential / 대한핵의학회잡지

The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.2.

Targeted Cancer Therapy Using Engineered Salmonella typhimurium / 전남의대학술지

Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

Clinical usefulness of post-operative 18F-fluorodeoxyglucose positron emission tomography-computed tomography in canine hemangiosarcoma

This report describes the usefulness of positron emission tomography-computed tomography (PET-CT) for evaluating recurrent or residual tumors following surgery. CT and 18F-fluorodeoxyglucose PET-CT were pre- and post-operatively applied to multiple masses in a dog with hemangiosarcoma. The distinction between the left subcutaneous mass and the peritoneum was clarified on pre-operative CT examination, and malignancy was suspected based on PET-CT. A recurrent or residual tumor in the left subcutaneous region was suspected on post-operative PET-CT, and confirmed through histopathologic examination.

Targeted Cancer Therapy Using Engineered Salmonella typhimurium / 전남의대학술지

Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

Clinical and histological patterns of dermatofibroma without gross skin surface change: A comparative study with conventional dermatofibroma.

Backg round: Dermatofibroma sometimes clinically presents as a nodular lesion without gross skin surface change. Clinicopathologic features of this variant of dermatofi broma have not been evaluated. Aims: To assess clinicopathologic features of dermatofi broma presenting as a subcutaneous nodule. Methods: This study reviewed the clinical and histological features of 42 cases of subcutaneous dermatofibromas and compared them with 95 cases of conventional dermatofi broma. Results: Dermatofi broma without gross skin surface change was associated with a shorter pre-diagnosis duration than conventional dermatofi broma. Increase in size during the pre-diagnosis period was signifi cantly more frequent in the conventional type. In addition, these dermatofi bromas were more likely than the conventional type to occur in the head and neck region. Although tumor depth was deeper than in the conventional type, less than half of the dermatofi bromas without gross skin surface change were found histologically to be “subcutaneous” or “deep-penetrating dermatofi broma”. Subcutaneous extension was more frequent in these dermatofi bromas while focal stromal hyalinization and hemosiderin deposits were more common in the conventional type. Limitations: This study is a retrospective, single center design. Conclusion: The present study suggests that dermatofi broma without gross skin surface change is a variant type with distinct clinical and histological features that distinguish them from conventional dermatofi broma.

Predictive Efficacy of Interim Positron Emission Tomography/Computed Tomography (PET/CT) for the Treatment of Aggressive Lymphoma / 전남의대학술지

The prognostic value of whole-body positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxy-D-glucose (FDG) shortly after the onset of induction chemotherapy or mid treatment could help to predict long-term clinical outcomes in patients with Hodgkin's or Non-Hodgkin's lymphoma. However, FDG is not a tumor-specific substance, and it may accumulate to the point of being detected in a variety of benign conditions or at physiologic anatomical sites, which may give rise to false-positive interpretation. In an attempt to standardize the reporting criteria for interim PET/CT, the First International Workshop on Interim PET in Lymphoma suggested visual response criteria with the Deauville five-point scale, and the standardized uptake value (SUV) has been investigated in comparison with this visual system. A quantitative approach using the measurement of maximal SUV (SUVmax) or the reduction rate of SUVmax (DeltaSUVmax) might be more appropriate in early-response PET/CT for reducing false-positive rates or for decreasing interobserver variability in interpretation. In this review, the predictive efficacy of PET/CT is discussed for the treatment of aggressive lymphoma, especially in terms of an interim PET/CT-based prognostic model.

Predictive Efficacy of Interim Positron Emission Tomography/Computed Tomography (PET/CT) for the Treatment of Aggressive Lymphoma / 전남의대학술지

The prognostic value of whole-body positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxy-D-glucose (FDG) shortly after the onset of induction chemotherapy or mid treatment could help to predict long-term clinical outcomes in patients with Hodgkin's or Non-Hodgkin's lymphoma. However, FDG is not a tumor-specific substance, and it may accumulate to the point of being detected in a variety of benign conditions or at physiologic anatomical sites, which may give rise to false-positive interpretation. In an attempt to standardize the reporting criteria for interim PET/CT, the First International Workshop on Interim PET in Lymphoma suggested visual response criteria with the Deauville five-point scale, and the standardized uptake value (SUV) has been investigated in comparison with this visual system. A quantitative approach using the measurement of maximal SUV (SUVmax) or the reduction rate of SUVmax (DeltaSUVmax) might be more appropriate in early-response PET/CT for reducing false-positive rates or for decreasing interobserver variability in interpretation. In this review, the predictive efficacy of PET/CT is discussed for the treatment of aggressive lymphoma, especially in terms of an interim PET/CT-based prognostic model.

Targeting Orthotopic Glioma in Mice with Genetically Engineered Salmonella typhimurium

OBJECTIVE: With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor models. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium (S. typhimurium) to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique. METHODS: U87 malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated S. typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft. RESULTS: The injected S. typhimurium exclusively localized in the glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of S. typhimurium in the brain tumors. CONCLUSION: The present study demonstrated that S. typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.

Changes in 18F-Fluorodeoxyglucose Uptake in the Spinal Cord in a Healthy Population on Serial Positron Emission Tomography/Computed Tomography / 전남의대학술지

We aimed to determine the changes in 18F-fluorodeoxyglucose (FDG) uptake in the spinal cord on two serial positron emission tomography/computed tomography (PET/CT) scans in a healthy population. We retrospectively enrolled healthy people who underwent PET/CT twice for cancer screening. We excluded those who had degenerative vertebral disease, neurologic disease, or a history of a vertebral operation. The standardized uptake value (SUVmax) of the spinal cord of each mid-vertebral body was obtained by drawing a region of interest on an axial image of PET/CT. For analysis, the cord-to-background ratio (CTB) was used (CTB=SUVmax of each level/SUVmax of L5 level). Differences in pattern, sex, age, and intervals of the two serial PET/CT scans were analyzed. A total of 60 PET/CT images of 30 people were analyzed. The mean interval between the two PET/CT imaging studies was 2.80+/-0.94 years. On the follow-up PET/CT, significant change was shown only at the level of the C6 and T10 vertebrae (p<0.005). Mean CTB showed a decreasing pattern from cervical to lumbar vertebrae. There were two peaks at the lower cervical level (C4-6) and at the lower thoracic level (T12). Neither sex nor age significantly affected CTB. The FDG uptake of the spinal cord changed significantly on follow-up PET/CT only at the level of the C6 and T10 vertebrae. This finding is valuable as a baseline reference in the follow-up of metabolic changes in the spinal cord.

Clinical Usefulness of 18F-FDG PET/CT in the Detection of Early Recurrence in Treated Cervical Cancer Patients with Unexplained Elevation of Serum Tumor Markers / 전남의대학술지

We investigated the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for restaging of treated uterine cervix squamous cell cancer with tumor maker elevation that was not explained by other conventional evaluation. We enrolled 32 cases who underwent PET/CT for the restaging of treated cervical cancer with tumor marker elevation that was not explained by recent conventional evaluation. All enrolled cases had squamous cell carcinoma. Increased tumor markers included squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA). PET/CT findings were determined by pathologic confirmation or clinical follow-up. We compared PET/CT accuracy and clinical parameters including normalization of tumor markers in both the SCC Ag elevation group and the CEA elevation group. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT in detecting recurrence were 100%, 83.3%, 82.4%, and 100%, respectively. Accuracy was significantly different between the SCC Ag elevation group and the CEA elevation group (p=0.0169). PET/CT with SCC Ag elevation was more accurate (100%) than PET/CT with CEA elevation (66.7%). Normalization of tumor markers was observed more often in the SCC Ag elevation group than in the CEA elevation group (p=0.0429). PET/CT showed high negative predictive value and sensitivity in the restaging of cervical cancer with unexplained tumor marker elevation. PET/CT was more accurate in patients with SCC Ag elevation than in those with CEA elevation.

Clinical Usefulness of 18F-FDG PET/CT in the Detection of Early Recurrence in Treated Cervical Cancer Patients with Unexplained Elevation of Serum Tumor Markers / 전남의대학술지

We investigated the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for restaging of treated uterine cervix squamous cell cancer with tumor maker elevation that was not explained by other conventional evaluation. We enrolled 32 cases who underwent PET/CT for the restaging of treated cervical cancer with tumor marker elevation that was not explained by recent conventional evaluation. All enrolled cases had squamous cell carcinoma. Increased tumor markers included squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA). PET/CT findings were determined by pathologic confirmation or clinical follow-up. We compared PET/CT accuracy and clinical parameters including normalization of tumor markers in both the SCC Ag elevation group and the CEA elevation group. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT in detecting recurrence were 100%, 83.3%, 82.4%, and 100%, respectively. Accuracy was significantly different between the SCC Ag elevation group and the CEA elevation group (p=0.0169). PET/CT with SCC Ag elevation was more accurate (100%) than PET/CT with CEA elevation (66.7%). Normalization of tumor markers was observed more often in the SCC Ag elevation group than in the CEA elevation group (p=0.0429). PET/CT showed high negative predictive value and sensitivity in the restaging of cervical cancer with unexplained tumor marker elevation. PET/CT was more accurate in patients with SCC Ag elevation than in those with CEA elevation.

Changes in 18F-Fluorodeoxyglucose Uptake in the Spinal Cord in a Healthy Population on Serial Positron Emission Tomography/Computed Tomography / 전남의대학술지

We aimed to determine the changes in 18F-fluorodeoxyglucose (FDG) uptake in the spinal cord on two serial positron emission tomography/computed tomography (PET/CT) scans in a healthy population. We retrospectively enrolled healthy people who underwent PET/CT twice for cancer screening. We excluded those who had degenerative vertebral disease, neurologic disease, or a history of a vertebral operation. The standardized uptake value (SUVmax) of the spinal cord of each mid-vertebral body was obtained by drawing a region of interest on an axial image of PET/CT. For analysis, the cord-to-background ratio (CTB) was used (CTB=SUVmax of each level/SUVmax of L5 level). Differences in pattern, sex, age, and intervals of the two serial PET/CT scans were analyzed. A total of 60 PET/CT images of 30 people were analyzed. The mean interval between the two PET/CT imaging studies was 2.80+/-0.94 years. On the follow-up PET/CT, significant change was shown only at the level of the C6 and T10 vertebrae (p<0.005). Mean CTB showed a decreasing pattern from cervical to lumbar vertebrae. There were two peaks at the lower cervical level (C4-6) and at the lower thoracic level (T12). Neither sex nor age significantly affected CTB. The FDG uptake of the spinal cord changed significantly on follow-up PET/CT only at the level of the C6 and T10 vertebrae. This finding is valuable as a baseline reference in the follow-up of metabolic changes in the spinal cord.

Both F-18 FDG-avidity and malignant shape of cervical lymph nodes on PET/CT after total thyroidectomy predict resistance to high-dose I-131 therapy in patients with papillary thyroid cancer

Resistance of metastatic lymph nodes [LNs] to high dose I-131 therapy is associated with high morbidity in patients with differentiated thyroid cancer. We evaluated the role of F-18 FDG PET/CT in the prediction of resistance to high dose I-131 therapy in patients with papillary thyroid cancer. The subjects were 307 patients who underwent total or near total thyroidectomy followed by high dose [5.55-6.66 GBq] I-131 therapy. We divided the patients into three subgroups by visual assessment of regional LNs: FDG-avid LNs with a malignant shape on CT [PET/CT-positive group], FDG-avid LNs with a benign shape on CT [PET/CT-intermediate group] and no FDG-avid lesion [PET/CT-negative group]. We measured the maximum SUV [SUVmax] of FDG-avid LNs in each patient. The presence or absence of focal increased uptake of I-131 was evaluated by whole body scan [WBS], and was denoted as WBS-positive group or WBS-negative group, respectively. Resistance to therapy was defined as presence of thyroglobulin [Tg] in serum [Tg >/= 1.0 ng/ml] 3-6 months after I-131 therapy. Univariate and multivariate analyses were performed to determine the relationship between resistance to I-131 therapy and various clinico-pathologic variables. PET/CT-positive, intermediate, and negative groups included 20 [6.5%], 44 [14.3%] and 243 [79.2%] patients, respectively. The mean SUVmax was significantly higher in the PET/CT-positive group than that of the PET/CT-intermediate group [4.6 vs.2.7, P <0.001]. Univariate analysis revealed that the PET/CT-positive group [P <0.001], T2-4 stage [P <0.001], N1b stage [P = 0.001], lower dose [5.55 GBq] of I-131 [P <0.001], and the WBS-positive group [P = 0.029] were associated with resistance to therapy. In multivariate analysis, the PET/CT-positive group, lower dose of I-131, N1b stage, and T2-4 stage remained significant with odds ratios of 10.07 [P <0.001], 3.82 [P <0.001], 3.58 [P = 0.001], and 2.53 [P = 0.009], respectively. FDG-avidity and malignant shape of cervical LNs on pre-therapy FDG PET/CT were a strong risk factors predicting resistance to high dose I-131 therapy. A lower dose of administered I-131 [5.55 GBq] and more extensive tumors [T2-4 and N1b] were also associated with resistance to high dose I-131 therapy

Enhancement of antitumor effect using dendritic cells activated with natural killer cells in the presence of Toll-like receptor agonist

Dendritic cells (DCs) play a role in natural killer (NK) cell activation, while NK cells are also able to activate and mature DCs. Toll-like receptors (TLRs) on the surface of DCs and NK cells induce the maturation and activation of these cells when engaged with their cognate ligand. We investigated to generate potent DCs by maturation with NK cells in the presence of TLR agonist in vitro and tested the efficacy of these DC vaccinations in mouse colon cancer model. The optimal ratios of DCs versus NK cells were 1:1 to 1:2. Immature DCs were mature with NK cells in the presence of lipopolysaccharide, which is TLR4 agonist, and further addition of IL-2 induced phenotypically and functionally mature bone marrow-derived DCs. These potent DCs exhibited not only high expression of several costimulatory molecules and high production of IL-12p40 and IL-12p70, but also high allogeneic T cells stimulatory capacity, and the induction of the high activities to generate tumor-specific CTLs. Consistently, vaccination with these DCs efficiently inhibited CT-26 tumor growth in mouse colon cancer model when compared to other vaccination strategies. Interestingly, combination therapy of these DC-based vaccines and with low-dose cyclophosphamide showed dramatic inhibition effects of tumor growth. These results suggest that the DCs maturated with NK cells in the presence of TLR agonist are potent inducer of antitumor immune responses in mouse model and may provide a new source of DC-based vaccines for the development of immunotherapy against colon cancer.