High metabolic heterogeneity on baseline 18FDG-PET/CT scan as a poor prognostic factor for newly diagnosed diffuse large B-cell lymphoma.

Metabolic heterogeneity (MH) can be measured using 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT), and it indicates an inhomogeneous tumor microenvironment. High MH has been shown to predict a worse prognosis for primary mediastinal B-cell lymphoma, whereas its prognostic value in diffuse large B-cell lymphoma (DLBCL) remains to be determined. In the current study, we investigated the prognostic values of MH evaluated in newly diagnosed DLBCL. In the training cohort, 86 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone-like chemotherapies were divided into low-MH and high-MH groups using receiver operating characteristic analysis. MH was not correlated with metabolic tumor volume of the corresponding lesion, indicating that MH was independent of tumor burden. At 5 years, overall survivals were 89.5% vs 61.2% (P = .0122) and event-free survivals were 73.1% vs 51.1% (P = .0327) in the low- and high-MH groups, respectively. A multivariate Cox-regression analysis showed that MH was an independent predictive factor for overall survival. The adverse prognostic impacts of high MH were confirmed in an independent validation cohort with 64 patients. In conclusion, MH on baseline 18FDG-PET/CT scan predicts treatment outcomes for patients with newly diagnosed DLBCL.

[Report in 2017 April ～ 2018 March].

Women physicians, scientists and nurses are addressing many problems encountered in the practice of their chosen fields. We carried out a survey of the women working in the nuclear medicine field. Two hundred and six professionals answered this questionnaire. The findings of our survey were that we have many female bosses (experts), a low number of sexual harassment issues and enough parental leave. Many members work very hard to practice in this field, but they do not have enough support from their hospitals or research centers, to join medical conferences. And almost a quarter of those surveyed thought it is hard to improve their careers after taking parental leave. A change of perception in how their male colleagues and counterparts regard women in the field of nuclear medicine is required. This change, along with women having a clear and realistic career plan are fundamental answers to the issues faced by women in nuclear medicine.

Serum level of soluble interleukin-2 receptor is positively correlated with metabolic tumor volume on 18 F-FDG PET/CT in newly diagnosed patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using 18 F-FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18 F-FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin-2 receptor (sIL-2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL-2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ≥150 cm3 or sIL-2R ≥ 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ≥150 cm3 and sIL-2R ≥1300 U/mL was significantly associated with worse 5-year overall survival and event-free survival. Importantly, each of sIL-2R <1300 U/mL or TMTV <150 cm3 identified patients with favorable prognosis among NCCN-IPI high-intermediate and high-risk group. Serum level of sIL-2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by 18 F-FDG PET/CT that can predict treatment outcomes of patients with DLBCL.

¹8F-FDG PET/CT imaging for a gastrointestinal mantle cell lymphoma with multiple lymphomatous polyposis.

Multiple lymphomatous polyposis (MLP) is an uncommon type of gastrointestinal lymphoma characterized by the presence of multiple polyps along the gastrointestinal tract. Most of this entity is in fact considered the counterpart of gastrointestinal tract involvement for mantle cell lymphoma (MCL). To our knowledge, there have been no reports on [fluorine-18]-fluorodeoxy-glucose ((18)F-FDG)-positron emission tomography (PET)/computed tomography (CT) imaging for gastrointestinal MCL with MLP. We present the results of (18)F-FDG PET/CT imaging in a patient with gastrointestinal tract involvement of MCL showing continuous MLP from the stomach to the rectum and intestinal intussusception. FDG-PET/CT findings were false negative in typical MLP spreading widely over the gastrointestinal tract, but uptake was noted in large lesions with deep infiltration considered atypical as MLP. On FDG-PET/CT imaging, the Ki-67 proliferative index, which is a cell proliferation marker, showed neither correlation with the presence of uptake nor the maximum standardized uptake value.

Isolated cardiac sarcoidosis requiring open-chest myocardial biopsy for differentiation from malignant lymphoma.

A 68-year-old woman with a history of hypertension was admitted to our hospital because of dyspnea during physical exertion. Echocardiography demonstrated impaired left ventricular systolic function, and her ejection fraction was reduced to 30%. Coronary angiography did not show significant stenosis. Endomyocardial biopsy showed only nonspecific findings without noncaseating granulomas. Cardiac magnetic resonance (CMR) imaging showed transmural late gadolinium enhancement on the basal part of the left ventricle. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) showed abnormal focal uptake specific to the left ventricle; no abnormal manifestations in other organs were observed. The CMR and 18F-FDG PET features could not rule out either sarcoidosis or malignant lymphoma. Therefore, we conducted open-chest myocardial biopsy to differentiate between the two possible diseases. Histopathological findings showed noncaseating epithelioid cell granuloma, confirming isolated cardiac sarcoidosis. This is an example of a challenging case of diagnosing isolated cardiac sarcoidosis. .

Observer variation study of the assessment and diagnosis of incidental colonic FDG uptake.

PURPOSE: The aim of this study was to evaluate the interpretations of incidental colonic 18F-FDG uptake made by 10 experienced readers and to more clearly identify the pattern of suspicious colonic FDG uptake. The potential contributions of delayed FDG-PET scanning and of immune fecal occult blood testing (FOBT) in making a diagnosis were also analyzed. MATERIALS AND METHODS: Visual interpretations by 10 readers were made for 147 FDG uptake sites from 126 PET scans (cancer, 38 sites; adenoma, 43 sites; and no abnormality, 66 sites) with colonic FDG uptake. Assessments for the early FDG-PET images were (1) FDG uptake pattern, (2) FDG uptake degree, and (3) likelihood of malignancy. For the delayed images, the assessments were (1) change in the FDG uptake position, (2) change in FDG uptake degree, and (3) likelihood of malignancy. The results of FOBT were analyzed independently of the visual interpretations. RESULTS: Interobserver agreement (κ) was 0.501 for assessing FDG uptake patterns, while agreement on assessing changes in uptake degree and changes in uptake position between early and delayed imaging were low (κ = 0.213-0.229). Logistic regression analysis indicated that 'FDG uptake patterns' and 'FDG uptake degree' were significantly related to decide on the suspicion of malignancy (p < 0.001) and the final result (p < 0.001). "Small localized" and "large irregular localized" types had a high probability of a lesion regardless of either (1) FDG uptake degree or (2) variation in the uptake between the early and the delayed image. The delayed image decreased false-positive cases for some FDG uptake patterns, but it had little impact on distinguishing clearly between "cancer or adenoma" and "normal". The addition of FOBT had little impact on the diagnosis. CONCLUSION: There was highest agreement among readers with respect to the recognition of specified colonic FDG uptake patterns, and this pattern recognition had the most influence on the diagnosis. "Small localized" and "large irregular localized" types had a high probability of a lesion. The addition of delayed imaging and of FOBT results to the early imaging did not have much impact on the diagnosis.

The current status of an FDG-PET cancer screening program in Japan, based on a 4-year (2006-2009) nationwide survey.

OBJECTIVE: The aim of this study was to survey the 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening program conducted in Japan. METHODS: The "FDG-PET cancer screening program" included both FDG-PET and positron emission tomography with computed tomography (PET/CT) with or without other combined screening tests that were performed for cancer screening in asymptomatic subjects. A total of 155,456 subjects who underwent the FDG-PET cancer screening program during 2006-2009 were analyzed. RESULTS: Of the 155,456 subjects, positive findings suggesting possible cancer were noted in 16,955 (10.9 %). The number of cases with detected cancer was 1,912 (1.23 % of the total screened cases, annual range 1.14-1.30 %). Of the 1,912 cases of detected cancer, positive findings on FDG-PET were present in 1,491 cases (0.96 % of the total number of screened cases). According to the results of further examinations, the true positive rate for subjects with suggested possible cancer (positive predictive value) was 32.3 % with FDG-PET. Cancers of the colon/rectum, thyroid, lung, and breast were most frequently found (396, 353, 319, and 163 cases, respectively) with high PET sensitivity (85.9, 90.7, 86.8, 84.0 %, respectively). Prostate cancer and gastric cancer (165 and 124 cases, respectively) had low PET sensitivity (37.0 and 37.9 %, respectively). The Union for International Cancer Control (UICC) clinical stage of cancer found with the FDG-PET cancer screening program was mainly Stage I. CONCLUSIONS: The FDG-PET screening program in Japan has detected a variety of cancers at an early stage. However, several cancers were found in repeated FDG-PET cancer screening program, indicating the limitation of a one-time FDG-PET cancer screening program. The value of the FDG-PET cancer screening program is left to the judgment of individuals with regard to its potentials and limitations.

Radiation exposure and risk-benefit analysis in cancer screening using FDG-PET: results of a Japanese nationwide survey.

OBJECTIVE: The aim of this study was to estimate radiation exposure and evaluate the risks and benefits of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in cancer screening. METHODS: A nationwide survey of FDG-PET cancer screening was conducted in 2006, and the results were analyzed with a common index, "extension/shortening of the average life expectancy." RESULTS: The average estimated effective dose was 4.4 mSv (male 4.7 mSv; female 4.0 mSv) for dedicated PET and 13.5 mSv (male 14.2 mSv; female 12.8 mSv) for PET/computed tomography (CT). The risk-benefit break-even age from the viewpoint of radiation exposure was in the 40s for men and 30s for women for dedicated PET and in the 50s for men and 50s (variable injection dose) or 60s (constant injection dose) for women for PET/CT. CONCLUSIONS: FDG-PET cancer screening is beneficial for examinees above the break-even ages. The risks and benefits should be explained to examinees because of the larger radiation used in cancer FDG-PET screening compared with other X-ray tests.

Analysis of various malignant neoplasms detected by FDG-PET cancer screening program: based on a Japanese Nationwide Survey.

OBJECTIVE: The most distinctive feature of FDG-PET cancer screening program is the ability to find various kinds of malignant neoplasms in a single test. The aim of this survey is to clarify the range and frequency of various malignant neoplasms detected by FDG-PET cancer screening performed in Japan. METHODS: "FDG-PET cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. This survey was based on a questionnaire regarding FDG-PET cancer screening. We analyzed the situation of 9 less frequently found malignant neoplasms including malignant lymphoma, malignancy of head and neck, esophagus, hepatobiliary and gallbladder, pancreas, kidney, cervical and uterine, ovary, and bladder. RESULTS: The detailed information of subjects with the suspected 9 kinds of malignant neoplasms mentioned above in the FDG-PET cancer screening program was studied in a total of 1,219 cases from 212 facilities. A statistical significance between PET/CT and PET was found in relative sensitivity and PPV for renal cell cancer. Malignant lymphoma was frequently of indolent type, suspected head and neck cancers had many false-positive results, and pancreatic cancer detected in this program was often in the advanced stage even in asymptomatic subjects. The recommendation of combined screening modality to PET or PET/CT was as follows: gastric endoscopy for assessing early esophageal cancer; abdominal ultrasound for screening hepatobiliary and gallbladder cancer; pelvic magnetic resonance imaging for assessing gynecological and pelvic cancers; and the CA125 blood test for screening ovarian cancer. Delayed image was helpful depending on the type of suspected malignant neoplasm. CONCLUSION: We analyzed various types of malignant neoplasms detected by the FDG-PET cancer screening program and presented recommended combination of examinations to cover FDG-PET and PET/CT.

Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis.

PURPOSE: Despite accumulating reports on the clinical value of (18)F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging (MRI) in the assessment of cardiac sarcoidosis, no studies have systematically compared the images of these modalities. METHODS: Twenty-one consecutive patients with suspected cardiac sarcoidosis underwent cardiac examinations that included 18F-FDG PET and MRI. The association of 18F-FDG PET and MRI findings with blood sampling data such as serum angiotensin converting enzyme levels was also evaluated. RESULTS: Eight of 21 patients were diagnosed as having cardiac sarcoidosis according to the Japanese Ministry of Health and Welfare Guidelines for Diagnosing Cardiac Sarcoidosis. Sensitivity and specificity for diagnosing cardiac sarcoidosis were 87.5 and 38.5%, respectively, for 18F-FDG PET, and 75 and 76.9%, respectively, for MRI. When the 18F-FDG PET and MRI images were compared, 16 of 21 patients showed positive findings in one (n = 8) or both (n = 8) of the two modalities. In eight patients with positive findings on both images, the distribution of the findings differed among all eight cases. The presence of positive findings on 18F-FDG PET was associated with elevated serum angiotensin-converting enzyme levels; this association was not demonstrated on MRI. CONCLUSIONS: Both 18F-FDG PET and MRI provided high sensitivity for diagnosing cardiac sarcoidosis in patients with suspected cardiac involvement, but the specificity of (18)F-FDG PET was not as high as previously reported. The different distributions of the findings in the two modalities suggest the potential of 18F-FDG PET and MRI in detecting different pathological processes in the heart.

Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey.

OBJECTIVE: The aim of this study is to survey the situation of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening in Japan and to describe its performance profile. METHODS: "FDG-PET for cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. We sent questionnaires regarding FDG-PET cancer screening to 99 facilities in which FDG-PET tests were performed during the fiscal year 2005. Replies were obtained from 68 of the 99 facilities, of which 46 facilities performed FDG-PET cancer screening. The total number of subjects who underwent FDG-PET cancer screening was 50 558. From 38 of 46 facilities, reliable results of thorough examinations were obtained for the subjects who were positive by FDG-PET and/or one or more of the combined screening tests was performed and were referred for further evaluation. The total number of subjects in these 38 facilities amounted to 43 996. RESULTS: A total of 50,558 healthy subjects underwent FDG-PET (including PET/CT) scanning with or without other tests for cancer screening in 46 PET centers during the fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases as a result of positive findings suggesting possible cancer. On analyzing 43 996 cases from 38 PET centers from which detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% were PET positive and 0.24% were PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of the thyroid, colon/rectum, lung, and breast were most frequently found (107, 102, 79, and 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, and 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had a better detection rate, sensitivity, and positive predictive value than dedicated PET (P < 0.01). CONCLUSIONS: We were able to clarify the performance profile of "FDG-PET for cancer screening" on the basis of a Japanese nationwide survey. The number of facilities possessing PET is increasing steadily, highlighting the necessity of evaluating the usefulness of "FDG-PET cancer screening" as soon as possible by undertaking long-term investigations of large series of subjects.

[Performance profile of FDG-PET and PET/CT for cancer screening based on a Japanese nationwide survey].

A total of 50,558 healthy subjects underwent an FDG-PET (including PET/CT) scan with or without combination of other tests for cancer screening in 46 PET centers during fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases due to positive findings suggesting possible cancer. On analyzing 43,996 cases from 38 PET centers, where detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% was PET positive and 0.24% was PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of thyroid, colon/rectum, lung and breast were most frequently found (107, 102, 79, 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had better detection rate, sensitivity, and positive predictive value than dedicated PET (p<0.01).

PET/CT today: system and its impact on cancer diagnosis.

Over the past six years, PET/CT has spread rapidly and replaced conventional PET. Although PET/CT is a combination of PET for functional information and CT for morphological information, their combination is synergistic. PET/CT fusion images result in higher diagnostic accuracy with fewer equivocal findings. This results in a greater impact on cancer diagnosis. With attenuation correction performed by the CT component, PET/CT can provide higher quality images over shorter examination times than conventional PET. As with all modalities, PET/CT has several characteristic artifacts such as misregistration due to respiration, overattenuation correction due to metals, etc. Awareness of these pitfalls will help the imaging physician use PET/CT effectively in daily practice.

Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis.

AIMS: To evaluate the value of (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) in detecting cardiac sarcoidosis. METHODS AND RESULTS: Thirty-two patients with sarcoidosis and thirty controls were recruited. All subjects underwent cardiac (18)F-FDG PET after a 6 h fasting period, and subjects with sarcoidosis underwent blood testing, ECG, echocardiography, and (67)Ga and (99m)Tc-sestamibi (MIBI) scintigraphy. We classified (18)F-FDG PET images into four patterns ('none', 'diffuse', 'focal', and 'focal on diffuse') and found that all the control subjects exhibited either none (n=16) or diffuse (n=14) pattern. In contrast, fifteen subjects with sarcoidosis exhibited none, seven exhibited diffuse, eight exhibited focal, and two exhibited focal on diffuse patterns, with the prevalence of the focal and focal on diffuse patterns being significantly higher in the sarcoidosis group when compared with the control group (P<0.001). None of the 32 subjects with sarcoidosis exhibited abnormal findings on (67)Ga scintigraphy, and 4 exhibited abnormal findings on (99m)Tc-MIBI scintigraphy. CONCLUSION: Focal uptake of the heart on (18)F-FDG PET images is a characteristic feature of patients with sarcoidosis. Furthermore, (18)F-FDG PET has the potential to detect cardiac sarcoidosis that cannot be diagnosed by (67)Ga or (99m)Tc-MIBI scintigraphy.

18F-FDG PET is superior to 67Ga SPECT in the staging of non-Hodgkin's lymphoma.

OBJECTIVE: Our study aims to compare diagnostic accuracy between 18F-FDG PET and 67Ga SPECT in the staging of non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with non-Hodgkin's lymphoma, underwent 18F-FDG PET, 67Ga SPECT and CT for the pretreatment staging of malignant lymphoma between August 1999 and March 2002. 18F-FDG PET imaging was obtained 60 minutes after the intravenous administration of 185 MBq of 18F-FDG. 67Ga SPECT imaging was obtained 2 days after the intravenous administration of 148 MBq of 67Ga. 18F-FDG PET and 67Ga SPECT were performed within one month. Both imagings were performed on the area from the neck to the pelvis. The 18F-FDG PET and 67Ga SPECT findings were compared with the CT findings and the clinical course. RESULTS: Sixty-six nodal lesions were clinically confirmed. Of these, 32 were identified by both 18F-FDG PET and 67Ga SPECT. The remaining 34 lesions were identified only by 18F-FDG PET. The mean (+/- SD) sizes' of the nodes were 34.7 +/- 32.4 mm for 18F-FDG-positive and 67Ga-positive lesions and 15.7 +/- 8.3 mm for 18F-FDG-positive and 67Ga-negative lesions (p < 0.001). Of the 23 extranodal lesions, 12 were identified by both 18F-FDG PET and 67Ga SPECT, whereas 6 lesions were identified by only 18F-FDG PET. Five lesions were not identified by either technique. No 18F-FDG-negative but 67Ga-positive nodal or extranodal lesions were observed. The difference in findings between the two studies is related to the difference in the size but not in the histology or site of the lesions. CONCLUSION: 18F-FDG PET detected significantly more lesions particularly small lesions than 67Ga SPECT. Thus, 18F-FDG PET is considered to be superior to 67Ga SPECT in the staging of non-Hodgkin' s lymphoma.

Mediastinal lymph node staging by FDG-PET in patients with non-small cell lung cancer: analysis of false-positive FDG-PET findings.

BACKGROUND: Accurate staging of mediastinal and hilar lymph nodes is a critical factor determining operability in patients with non-small cell lung cancer (NSCLC). Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer (FDG-PET) has recently been reported to be more effective in detecting tumor involvement in mediastinal and hilar lymph nodes than computed tomography (CT). OBJECTIVE: In this study, we analyzed the accuracy of FDG-PET in mediastinal and hilar lymph node staging in patients with NSCLC and the factors associated with false-positive or false-negative FDG-PET findings in mediastinal and hilar lymph node staging. METHODS: Fifty-four patients with NSCLC who underwent preoperative analysis including chest CT and whole-body FDG-PET were evaluated retrospectively. Using FDG-PET, lesions were considered to be positive if a definite, localized area of higher uptake, excluding physiologic uptake, than in surrounding normal tissue was present. On CT findings, lymph nodes were considered to be positive if they were >10 mm in short-axis diameter, except subcarinal lymph nodes (#7), which were considered to be positive if they were >15 mm in short-axis diameter. All patients underwent surgical resection of primary tumors and mediastinal and hilar lymph nodes between 1999 and 2001 in our institute. Resected lymph nodes were histologically examined for the existence of tumor cells. RESULTS: A total of 306 lymph nodes were resected and used for analysis. The sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET were 73, 98, 70 and 98%, while those of CT were 55, 96, 55 and 96%, respectively. When pre-operative nodal staging was compared with post-operative histopathological staging, 44 patients (81%) were correctly staged, 7 (13%) were overstaged and 3 (6%) were understaged by FDG-PET, while 39 patients (72%) were correctly staged, 8 (15%) were overstaged and 7 (13%) were understaged by CT. All 7 overstaged patients by FDG-PET had other pulmonary complications, including interstitial pneumonitis (n = 2), previous pulmonary tuberculosis (n = 3), silicosis (n = 1) and emphysema (n = 1), although they were not in the active stage. In 3 understaged patients by FDG-PET, lymph nodes were also undetectable by CT. CONCLUSION: FDG-PET is superior to CT in mediastinal and hilar lymph node staging of patients with NSCLC. However, care should be taken in lymph node staging for patients who have other pulmonary complications, including interstitial pneumonitis, previous pulmonary tuberculosis and silicosis.

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

UNLABELLED: 1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. METHODS: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were 0.8. RESULTS: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001). CONCLUSION: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.

Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with 99mTc-annexin V.

UNLABELLED: Annexin V, a human protein with a high affinity for phosphatidylserine, has been labeled with (99m)Tc to detect apoptosis in vivo. To determine the effectiveness of imaging with this agent as a reflection of the degree of apoptosis after the first dose of chemotherapy, we studied rats with an engrafted hepatoma. METHODS: Annexin V was labeled with (99m)Tc (specific activity, 3.0 MBq/ micro g protein). Eleven days after being inoculated with allogenic hepatoma cells (KDH-8) in the left calf muscle, the rats were randomized to receive a single dose of cyclophosphamide (150 mg/kg intraperitoneally) or to serve as controls. (99m)Tc-annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h after injection of (99m)Tc-annexin V. Tumor uptake of (14)C-iodoanitpyrine was determined as a marker of tumor blood flow. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) of tissue harvested at necropsy was performed to detect apoptosis in the tumor. RESULTS: Cyclophosphamide treatment significantly increased the tumor uptake (percentage activity of injected dose per gram of tissue after normalization to the animal's weight [%ID/g/kg]) of (99m)Tc-annexin V (0.070 +/- 0.007 %ID/g/kg for treated rats and 0.046 +/- 0.009 %ID/g/kg for controls, P < 0.001). (14)C-iodoantipyrine uptake was similar in the treated and untreated groups. The number of TUNEL-positive cells in the tumor was significantly larger in the treated rats (297.70 +/- 50.34 cells/mm(2)) than in the control rats (168.45 +/- 23.60 cells/mm(2), P < 0.001). Tumor uptake of (99m)Tc-annexin V correlated with the number of TUNEL-positive cells in the tumor (r = 0.712; P < 0.001). CONCLUSION: Tumor uptake of (99m)Tc-annexin V was significantly increased by a single dose of cyclophosphamide treatment, and the increase was concordant with the number of TUNEL-positive cells in the tumor. The current results are suggestive of the utility of (99m)Tc-annexin V as a noninvasive means to assess tumor response, although further testing, including clinical evaluation, is required.