Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

OBJECTIVE: The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases. SUBJECTS AND METHODS: Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after. RESULTS: The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers. CONCLUSION: Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.

Correlations between dual-phase 18F-FDG uptake and clinicopathologic and biological markers of breast cancer.

OBJECTIVE: To assess the correlations between dual-phase fluorine-18 fluorodeoxyglucose (18F-FDG) uptake and clinicopathological and immunohistochemical prognostic factors in patients with surgically resected breast cancer. SUBJECTS AND METHODS: We retrospectively analyzed the cases of 105 patients. We calculated the maximum standardized uptake value (SUVmax) at 85min (SUV1), SUVmax at 125min (SUV2) and the retention index [RI]. Spearman's rank correlation test, the Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were performed to assess the association between 18F-FDG uptake and the clinicopathological and immunohistochemical factors: glucose transporter-1 (Glut-1), estrogen receptor alpha (ERα), ERß, progesterone receptor (PR), human epidermal growth factor 2 (Her2), mammalian target of rapamycin (mTOR), and P70S6kinase (P70S6). RESULTS: The SUV1 and SUV2 values were correlated with Glut-1, pathological tumor size, ERα negativity, and pathological stage (all P values were <0.05), but not with mTOR, P70S6, ERß, PR, Her2 or other factors. The SUV1 and SUV2 in the triple negative subtype were significantly higher than those of the hormone receptor-positive subtype (P<0.05). The RI was associated with pathological tumor size alone. In the ROC analysis of Glut-1, the areas under the curve for SUV1 and SUV2 were significantly larger than that for RI (SUV1, P=0.032, SUV2, P=0.022). CONCLUSION: Glucose transporter-1, estrogen receptor alpha negativity and nuclear grade might affect the high 18F-FDG uptake in breast cancer. The SUVmax might be more useful than the RI for predicting the Glut-1 expression and the aggressiveness of breast cancer.

¹8F-FDG PET/CT and contrast enhanced CT in differential diagnosis between leiomyoma and gastrointestinal stromal tumor.

In a 49 years old woman a large abdominal tumor was diagnosed by abdominal ultrasound. Dynamic contrast-enhanced computed tomography (CECT) showed a large tumor with minute calcification and poor contrast enhancement in the left abdominal cavity. The fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG PET/CT) scan showed low ¹8F-FDG uptake in the tumor. The SUV max (early image) was 1.90, and that of the delayed image was 2.86. A gastrointestinal stromal tumor (GIST) was suspected. Tumor resection revealed that it was a leiomyoma originating in the major curvature of the stomach. In conclusion, the findings of low ¹8F-FDG uptake on ¹8F-FDG PET and poor contrast enhancement on CECT in a gastric submucosal tumor suggested of a gastric leiomyoma rather than GIST.

Hypermetabolic pulmonary and bone marrow lesions in a patient with chronic adult T-cell leukemia.

A 69 years old woman with adult T-cell leukemia (ATL) (chronic type) was referred for a fluorine-18 fluorodeoxyglucose positron emission computed tomography ((18)F-FDG PET/CT). Multiple hypermetabolic pulmonary and bone lesions were evidence. The patient underwent chemotherapy, but did not respond, and she died approximately 8 months from the onset of symptoms. Autopsy showed ATL cells infiltrating the lung parenchyma and the pulmonary hilum. In conclusion, we present a case of hypermetabolic pulmonary lesions associated with thoracic CT findings on a (18)F-FDG PET/CT scan in a patient with a chronic adult T-cell leukemia.

Age-related changes in pre- and postmenopausal women investigated with 18F-fluoride PET--a preliminary study.

OBJECTIVE: To evaluate the relationship between age and regional skeletal uptake at sites consisting of either predominantly trabecular or cortical bone using (18)F-fluoride positron emission tomography (PET) in pre- and postmenopausal women. MATERIALS AND METHODS: Thirty-two women (40.6 ± 12.3 years; age range 25-72 years) were assigned to one of two groups: group 1 comprised 22 premenopausal women (33 ± 6.5 years; age range 25-48 years) and group 2 comprised 10 postmenopausal women (56 ± 6.7 years; age range 49-72 years). The maximum standardized uptake value (SUVmax) was determined from the lumbar spine and the humeral shaft. Student's t-test for each unpaired dataset was used to evaluate statistical differences between the two groups. The SUVmax values for the humeral shaft and the lumbar spine were compared with aging. RESULTS: The SUVmax (mean ± SD) was 1.2 ± 0.5 in the humeral shaft and 4.7 ± 1.0 in the lumbar spine. The SUVmax in the humeral shaft correlated significantly with advancing age (r = 0.67, P < 0.01). The SUVmax in the lumbar spine declined significantly with advancing age (r = -0.50, P < 0.01). The humeral shaft of women in group 1 exhibited a significantly lower SUVmax compared to that in group 2 (1.1 ± 0.4 versus 1.6 ± 0.6; P < 0.05). On the other hand, the lumbar spine of women in group 1 exhibited a significantly higher SUVmax compared to that in group 2 (5.1 ± 0.7 versus 4.0 ± 1.1; P < 0.05). The mean SUVmax in the lumbar spine was 2.5 times greater than that in the humeral shaft in group 2. CONCLUSION: Semiquantitative analysis with (18)F-fluoride PET might be a useful tool for analyzing age-related changes in pre- and postmenopausal women.

Incidental detection of rare mesenteric inflammatory pseudotumor by (18)F-FDG PET.

A 60 years old asymptomatic male underwent fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for his medical check-up, and abnormal (18)F-FDG uptake was observed in the retroperitoneum. The maximum standardized uptake value (SUV (max)) was 5.2. Based on CT, MRI and (18)F-FDG PET findings, the differential diagnosis included specific or non-specific inflammatory change, malignant lymphoma, trauma, gastrointestinal stromal tumor and soft-tissue sarcoma. Tumor resection was performed, and the histopathological finding was an inflammatory pseudotumor (IPT) originating at the mesentery in the retropetonium. After two years and eight months from his initial operation, recurrent IPT was detected by (18)F-FDG PET for follow-up, although he was asymptomatic. The IPT could be of traumatic origin since the patient suffered a severe abdominal trauma 6 months before. A mesenteric IPT is very rare, and to our knowledge, this is the first case report of (18)F-FDG PET detecting a mesenteric IPT. In conclusion, when abnormal high (18)F-FDG uptake is observed in the mesentery incidentally in clinical routine examination, IPT should be included as one of the differential diagnoses. (18)F-FDG may be useful in detecting local recurrence and follow-up after operation.

Functional connectivity between the amygdala and subgenual cingulate gyrus predicts the antidepressant effects of ketamine in patients with treatment-resistant depression.

AIM: Approximately one-third of patients with major depressive disorder develop treatment-resistant depression. One-third of patients with treatment-resistant depression demonstrate resistance to ketamine, which is a novel antidepressant effective for this disorder. The objective of this study was to examine the utility of resting-state functional magnetic resonance imaging for the prediction of treatment response to ketamine in treatment-resistant depression. METHODS: An exploratory seed-based resting-state functional magnetic resonance imaging analysis was performed to examine baseline resting-state functional connectivity differences between ketamine responders and nonresponders before treatment with multiple intravenous ketamine infusions. RESULTS: Fifteen patients with treatment-resistant depression received multiple intravenous subanesthetic (0.5 mg/kg/40 minutes) ketamine infusions, and nine were identified as responders. The exploratory resting-state functional magnetic resonance imaging analysis identified a cluster of significant baseline resting-state functional connectivity differences associating ketamine response between the amygdala and subgenual anterior cingulate gyrus in the right hemisphere. Using anatomical region of interest analysis of the resting-state functional connectivity, ketamine response was predicted with 88.9% sensitivity and 100% specificity. The resting-state functional connectivity of significant group differences between responders and nonresponders retained throughout the treatment were considered a trait-like feature of heterogeneity in treatment-resistant depression. CONCLUSION: This study suggests the possible clinical utility of resting-state functional magnetic resonance imaging for predicting the antidepressant effects of ketamine in treatment-resistant depression patients and implicated resting-state functional connectivity alterations to determine the trait-like pathophysiology underlying treatment response heterogeneity in treatment-resistant depression.

Prognostic value of dual-point fluorine-18 fluorodeoxyglucose PET imaging, partial volume correction and glucose transporter-1 expression in resected nonsmall cell lung cancer patients.

OBJECTIVE: To investigate the relationship between the prognosis and glucose transporter-1 (Glut-1) expression or fluorine-18 fluorodeoxyglucose uptake using partial volume correction and dual-point imaging in surgically resected nonsmall cell lung cancer (NSCLC) patients. METHODS: Our patient population consisted of 108 NSCLC cases. The early maximum standardized uptake value (ESUVmax), delayed SUVmax (DSUVmax), partial volume correction SUVmax (cSUVmax) and retention index of primary lesions were calculated. Cox proportional hazard model was applied to evaluate the effects of PET parameters and Glut-1 expression. Overall survival (OS) and disease-free survival (DFS) were evaluated by Kaplan-Meier methods, and the difference in survival between subgroups was analyzed by log-rank test. RESULTS: On the Cox regression analysis, ESUVmax, DSUVmax, cSUVmax and Glut-1 were significantly related to DFS [ESUVmax, hazard ratio = 2.301, 95% confidential interval (CI) = 1.146-4.618, P = 0.019; DSUVmax, hazard ratio = 2.483, 95% CI = 1.257-4.905, P = 0.009; cSUVmax, hazard ratio = 2.205, 95% CI = 1.038-4.686, P = 0.04; Glut-1, hazard ratio = 2.095, 95% CI = 1.086-4.041, P = 0.001] and OS (ESUVmax, hazard ratio = 3.197, 95% CI = 1.339-7.633, P = 0.009; DSUVmax, hazard ratio = 3.599, 95% CI = 1.521-8.516, P = 0.004; cSUVmax, hazard ratio = 8.655, 95% CI = 2.048-36.658, P = 0.003; Glut-1, hazard ratio = 2.427, 95% CI = 5.140, P = 0.021). Retention index had no significant association with DFS or OS. On the Kaplan-Meier survival curves, the patients with high ESUVmax, DSUVmax, cSUVmax and Glut-1 showed significantly worse prognosis than those with low values (ESUVmax: DFS, P = 0.001, OS, P = 0.003; DSUVmax: DFS, P = 0.002, OS, P = 0.004; cSUVmax: DFS, P < 0.001, OS, P = 0.013; Glut-1: DFS, P = 0.012, OS, P = 0.002). CONCLUSIONS: cSUVmax, ESUVmax, DSUVmax and Glut-1 may be more useful biomarkers than retention index for predicting outcomes in NSCLC patients.

Inappropriate intracranial hemodynamics in the natural course of MELAS.

The abnormalities of intracranial hemodynamics associated with strokelike episodes in MELAS are variable depend on the time phase from the onset of strokelike episodes and on the progression of the dementia state. To clarify the regional cerebral blood flows (rCBF) in the natural course of MELAS is very important to understand the pathogenic mechanism of this disorder, either cytopathy, angiopathy or both. We analyzed the serial studies of brain statistical parametric mapping (SPM) 99 single photon emission computed tomography (SPECT) in 5 MELAS patients in maximum 10 years interval, who fulfilled the clinical, pathological and genetic criteria of MELAS, and have an A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. SPM is a proven and effective method for the voxel-by-voxel analysis of functional images which show the advantage in its promise of fully automated neurophysiological imaging analysis throughout the whole brain using various statistical analyses. SPECT acquisition was initiated and was reconstructed by iterative algorithm and were processed and analyzed with SPM 99 for Windows software. Statistics were displayed as Z scores (threshold: P < 0.01). The inappropriate intracranial hemodynamics was found not only at the acute but at the interictal phase, and was getting worse as the disease progress. Hypoperfusion in the posterior cingulate cortex was always observed (corrected P < 0.01) in MELAS patients, which is the typical finding reported in Alzheimer's disease. The inappropriate intracranial hemodynamics is a common feature and may be related with mitochondrial angiopathy in the natural course of MELAS.

Improved breast cancer detection of prone breast fluorodeoxyglucose-PET in 118 patients.

OBJECTIVE: To prospectively evaluate the breast cancer detection of prone breast positron emission tomography (PET) images in comparison with supine whole-body PET images. MATERIAL AND METHODS: One hundred and eighteen female patients (age range 28-91 years) with 122 lesions suspected of having breast cancer underwent fluorine-18 fluorodeoxyglucose PET for preoperative staging. After the whole-body image was acquired, prone breast PET imaging was performed. The findings from both images were compared with the histopathologic results. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy were used to compare the diagnostic accuracy of prone breast PET images with that of whole-body PET images. RESULTS: Sensitivity, specificity, positive predictive value, NPV, and accuracy of whole-body PET images were 83, 50, 97, 17, and 80%, and of prone breast PET images they were 95, 50, 96, 43, and 93%. Ten of 114 breast cancerous lesions (8.8%) were detected on prone breast PET images alone. Statistical difference was found between the sensitivity, accuracy, and NPV of prone breast PET images and those of whole-body PET images (P<0.0001 for sensitivity and accuracy and P<0.0009 for NPV). CONCLUSION: Our data about the 122 lesions, suspected of breast cancer, with regard to the usefulness of prone breast PET imaging indicate that prone breast PET images are effective in detecting breast cancer.

Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device.

OBJECTIVE: The aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device. METHODS: Between January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal (18)F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital. RESULTS: Of the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device. CONCLUSIONS: In cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future.

The assessment of correlation and prognosis among 18F-FDG uptake parameters, Glut1, pStat1 and pStat3 in surgically resected non-small cell lung cancer patients.

INTRODUCTION: To assess the correlation among 18F-FDG uptake, Glut1, pStat1 and pStat3, and to investigate the relationship between the prognosis and 18F-FDG uptake and these molecular markers in surgically resected non-small cell lung cancer (NSCLC) patients. RESULTS: Knockdown of Glut1 led to a significant increase in pStat1 expression. Glut1 expression positively correlated with the SUVmax, SUVmean, and TLG significantly (P<0.001). pStat3 expression negatively correlated with all PET parameters significantly (P<0.001). pStat1 had positive weak correlations with the SUVmax and SUVmean. All PET parameters and Glut1 were significantly associated with DFS (P<0.05). TLG, MTV, Glut1 and pStat1 were significantly associated with OS (P<0.05). CONCLUSION: pStat3 and Glut1 may be associated with 18F-FDG uptake mechanism. TLG, MTV, and Glut1 may be independent prognostic factors. METHODS: The SUVmax, SUVmean, MTV and TLG of primary lesions were calculated in 140 patients. The expressions of Glut1 and Stat pathway proteins in NSCLC cell lines were examined by immune blots. Excised tumor tissue was analyzed by immunohistochemistry. OS and DFS were evaluated by the Kaplan-Meier method. The difference in survival between subgroups was analyzed by log-rank test. The prognostic significance of clinicopathological, molecular and PET parameters was assessed by Cox proportional hazard regression analysis.

CT image fusion for 3D depiction of anatomic abnormalities of the hepatic hilum.

OBJECTIVE: The purpose of this article is to show how CT image fusion with 3D reconstruction is used to depict in detail the anatomic structures of the hepatic hilum in the presence of hepatobiliary abnormalities. CONCLUSION: CT image fusion is a comprehensive imaging technique for preoperative evaluation of the blood vessels and bile ducts of the hepatic hilum.

Tumor thrombus in the inferior vena cava from colon cancer detected by 18F-FDG-PET.

We present a case of inferior vena cava (IVC) tumor thrombus detected by fluorine- 18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET). A man underwent operations for the treatment of sigmoid colon cancer at the age of 63. Because tumor markers [carcinoembryonic antigen (CEA) and CA19-9] were increased at the age of 67, abdominal contrast-enhanced computed tomography (CT) was performed. CT revealed IVC dilatation, including a low-attenuation area. 18F-FDG-PET was performed to make the differential diagnosis between tumor thrombus and clot. 18F-FDG-PET showed that 18F-FDG had accumulated in the IVC region. We considered the IVC tumor thrombus because of the 18F-FDG uptake in the IVC region and the patient's clinical course. To our knowledge, there are a few reports concerning 18F-FDG-PET and IVC tumor thrombus. 18F-FDG-PET may be useful in diagnosing tumor thrombus.

Diffuse and diffuse-plus-focal uptake in the thyroid gland identified by using FDG-PET: prevalence of thyroid cancer and Hashimoto's thyroiditis.

OBJECTIVE: To investigate and evaluate the prevalence of incidental thyroid diffuse and diffuse-plus-focal fluorine-18 fluorodeoxyglucose (FDG) uptake in healthy subjects who underwent cancer screening on positron emission tomography (PET) scan, and also to evaluate the prevalence of thyroid cancer and Hashimoto's thyroiditis. METHODS: We carried out a retrospective review of 1626 subjects who underwent PET scanning at our institution. Diffuse uptake was defined as FDG uptake in the whole thyroid gland, whereas diffuse-plus-focal uptake was defined as a thyroid lesion with both diffuse uptake and focal FDG uptake. The maximum standardized uptake value of the thyroid lesions was recorded and reviewed. In each selected subject with positive thyroid FDG uptake, serum thyroid-stimulating hormone, thyroid hormone, and thyroid antibodies were measured. Fine needle aspiration cytology was performed on patients with a definite nodule using ultrasonography. RESULTS: Twenty-nine subjects (1.78%) were identified as having either diffuse FDG uptake (n = 25, 1.53%) or diffuse-plus-focal FDG uptake (n = 4, 0.24%). All subjects with diffuse FDG uptake were diagnosed as having Hashimoto's thyroiditis. In 1 of the 25 subjects with diffuse FDG uptake and two of the four with diffuse-plus-focal FDG uptake, histopathologic diagnosis showed papillary thyroid carcinoma associated with Hashimoto's thyroiditis. However, PET scan did not detect papillary carcinoma associated with Hashimoto's thyroiditis in one of the three subjects. CONCLUSIONS: Our results suggest that although diffuse FDG uptake usually indicates Hashimoto's thyroiditis, the risk of thyroid cancer must be recognized in both diffuse FDG uptake and diffuse-plus-focal FDG uptake on PET scan.

Pelvic inflammatory disease with periappendicitis in a pediatric patient.

Pelvic inflammatory disease (PID) is generally a disease of young, sexually active patients. However, there have been few reports of computed tomography (CT) and the histopathologic findings of periappendicitis with PID in children. We present a case of PID with periappendicitis in a 12-year-old girl. Her CT findings are described, and the histopathologic findings of periappendicitis are discussed.

[Development of automatic analysis for dynamic renal function study using computed tomographic (CT) images].

Determination of the region of interest (ROI) for dynamic renal function has been highly discordant among operators because of the dependence on factors such as the rate of injection of radioactive medicines, constitution, and renal function. To simplify this problem, we developed a computer algorithm that provides automatic analysis for both localization of the kidney and automatic determination of ROIs using computed tomographic (CT) images. The bilateral kidneys were extracted from enhanced CT images, and the CT pixel size was adjusted to dynamic renal function images. The template-matching technique was used for these images, and the kidney renal location was analyzed on additional functional images constructed by dynamic renal function images. As a result, we were able to obtain time-activity curves of both renal function and quantified glomerular filtration rate (GFR). In conclusion, the computer algorithm we developed was considered to provide reliable results, apart from the variability among operators, because of its good reproducibility.

Early gastric cancer and early colon cancer detected simultaneously by PET cancer screening incidentally.

We report a case of early gastric cancer and early colon cancer detected by positron emission tomography (PET) cancer screening. A 64-year-old male patient with an unremarkable past history except for hypertension and cerebrovascular disease underwent 18F-FDG PET for cancer screening. Images revealed increased uptake in the gastric antrum and sigmoid colon. Both areas appeared suspicious for neoplasm on subsequent fluoroscopy and endoscopy, and biopsies were positive for neoplasia at both sites. The gastric lesion was treated by distal gastrectomy and D2 lymphadenectomy and the colon cancer by endoscopic mucosal resection (EMR). Both surgical specimens were positive for cancer.

The correlation between FDG uptake and biological molecular markers in pancreatic cancer patients.

PURPOSE: We examined whether fluorine-18 fluorodeoxyglucose (FDG) uptake is related to the mammalian target of rapamycin (mTOR) signal pathway and its related proteins in pancreatic cancer patients. METHODS: We retrospectively studied 53 pancreatic cancer patients who underwent FDG positron emission tomography (PET) or FDG PET/CT, and complete curative surgical resection. The SUV max, the tumor to nontumor activity of pancreas [T/N (P)] ratio and the T/N of liver [T/N (L)] ratio were calculated. The expressions of glucose transporter-1(Glut-1) and mTOR pathway proteins in pancreas cell lines were examined by immune blots. Excised tumor tissue was analyzed by immunohistochemistry using monoclonal antibodies for Glut-1, epidermal growth factor receptor (EGFR), mTOR, p70S6kinase (p70S6) and S6 ribosomal protein (S6). RESULTS: The expressions of Glut-1, EGFR and p70S6 were significantly correlated with the SUV max, T/N (P) ratio and T/N (L) ratio. The expressions of mTOR and S6 were not correlated with all parameters. The expression of Glut-1 was positively correlated with the expressions of EGFR and p70S6, but not with mTOR or S6. S6 was positively correlated with p70S6. CONCLUSIONS: Glut-1, EGFR and p70S6 expressions are associated with the FDG uptake mechanism of pancreatic cancer. FDG uptake may predict the levels of EGFR and p70S6 expressions, and FDG uptake reflects glucose metabolism and cancer progression.