Improved Correlation of 18F-Flortaucipir PET SUVRs and Clinical Stages in the Alzheimer Disease Continuum with the MUBADA/PERSI-Based Analysis.

The Alzheimer disease (AD) continuum is a neurodegenerative disorder with cognitive decline and pathologic changes. Tau PET imaging can detect tau pathology, and 18F-flortaucipir PET imaging is expected to visualize progression through the stages of AD, for which quantitative assessment is essential. Two measurement methods, statistically defined multiblock barycentric discriminant analysis (MUBADA)/parametric estimation of reference signal intensity (PERSI) and anatomically defined tau meta-volume of interest (VOI)/cerebellar gray matter (CGM) for SUV ratio (SUVR), were compared in this study to assess their relationship to AD clinical stage using 2 open multicenter PET databases. Methods: Data were selected for 106 cases from 2 databases, AMED Preclinical AD study (AMED-PRE) (n = 15) and Alzheimer Disease Neuroimaging Initiative 3 (n = 91). The data of the participants were categorized into 4 groups based on the clinical criteria. Tau PET imaging was conducted using 18F-flortaucipir, and the 2 SUVR measurement methods, MUBADA/PERSI and tau meta-VOI/CGM, were compared among different clinical categories: amyloid-negative cognitively normal, preclinical AD, amyloid-negative mild cognitive impairment (MCI), and amyloid-positive MCI. Results: Significant differences were found between cognitively normal and preclinical AD, as well as between cognitively normal and amyloid-positive MCI and between amyloid-negative MCI and -positive MCI in SUVR derived by MUBADA/PERSI, whereas SUVR by tau meta-VOI/CGM did not provide significant differences between any pair. The tau meta-VOI/CGM method consistently provided higher SUVRs and larger individual variations than MUBADA/PERSI, with a mean SUVR difference of 0.136 for the studied databases. Conclusion: MUBADA/PERSI provided the SUVR of 18F-flortaucipir uptake with better association with the clinical severity of the AD continuum and with smaller variability. The results support the usefulness of MUBADA/PERSI as a quantitative measure of 18F-flortaucipir uptake in multicenter studies using different PET systems and scanning methods. However, limitations of the study include the small sample size and the unbalanced distribution among clinical categories in the AMED Preclinical AD study database.

Quantification of bone metabolic activity in the natural course of fractural lesions measured by quantitative SPECT/CT.

Objectives: While increased uptake at the bone fractural site gradually decreases over time on bone scans, the rate of change has not been quantitatively evaluated. The purpose of this study was to quantify the extent of bone metabolic changes in fractural lesions on bone SPECT/CT. Methods: We reviewed bone scans acquired by dedicated SPECT/CT and chose those scans in which quantitative SPECT/CT of the same range was acquired twice or more. We set the region of interest on lesions of bone fracture and degeneration, and measured the maximum standardized uptake value (SUVmax). From the SUVmax of lesions and the interval between scans, a value for 30-day change in SUVmax was calculated as ∆SUVmax30d. The relationship between preSUVmax, SUVmax for the first scan of the comparison, and ∆SUVmax30d was evaluated utilizing a linear least-squares method. Furthermore, we assessed the ability to differentiate between fracture and degeneration using receiver operating characteristics (ROC) analysis and the Mann-Whitney U test. All cases were then categorized into five groups according to preSUVmax. Values of p <0.05 were considered statistically significant. Results: We investigated 175 scans from 60 patients and analyzed scan combinations for 157 fractural lesions and 266 degenerative lesions. The relationship between preSUVmax of fractural lesions and ∆SUVmax30d was approximated as ∆SUVmax30d =-0.15×preSUVmax +1.35 (R 2=0.60, p<0.0001). Area under the curves for all cases, 30≤ preSUVmax, 20≤ preSUVmax <30, 15≤ preSUVmax <20, 10≤ preSUVmax <15, and preSUVmax <10 were 0.73, 0.89, 0.86, 0.80, 0.91, and 0.59, respectively. Median ∆SUVmax30d was significantly lower at fractural lesions than at degenerative lesions (-0.62 vs -0.04; p <0.0001). As for analyses of groups divided by preSUVmax, all median ∆SUVmax30d for fractural lesions were significantly lower than those of degenerative lesions except for the group with preSUVmax <10. Conclusion: The increased uptake at the fractural bone lesion observed in the quantitative bone SPECT/CT gradually decreased at the rate of SUV 0.15 per month, which showed a different trend with degenerative change.

Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer's disease.

OBJECTIVE: A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [18F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [18F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer's disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese. METHODS: Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [18F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [18F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments. RESULTS: No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 µGy/MBq) and the urinary bladder (127.3 ± 11.7 µGy/MBq). The effective dose was 26.8 ± 1.4 µSv/MBq. The parent form ([18F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [18F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01). CONCLUSION: The findings supported safety and efficacy of [18F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [18F]MK-6240 were consistent with those for non-Japanese populations. TRIAL REGISTRATION: Japan Pharmaceutical Information Center ID, JapicCTI-194972.

Atlas of non-pathological solitary or asymmetrical skeletal muscle uptake in [18F]FDG-PET.

Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is widely used in oncology and other fields. In [18F]FDG PET images, increased muscle uptake is observed owing exercise load or muscle tension, in addition to malignant tumors and inflammation. Moreover, we occasionally observe non-pathological solitary or unilateral skeletal muscle uptake, which is difficult to explain the strict reason. In most cases, we can interpret them as not having pathological significance. However, it is important to recognize such muscle uptake patterns to avoid misdiagnoses with pathological ones. Therefore, the teaching point of this pictorial essay is to comprehend the patterns of solitary or asymmetrical skeletal muscle uptake seen in routine [18F]FDG-PET scans. As an educational goal, you will be able to mention muscles where intense physiological [18F]FDG uptake can be observed, differentiate between physiological muscle uptake and lesion, and discuss with any physicians or specialists about uncertain muscle uptake.

Diffuse FDG uptake in the bilateral lungs: hypersensitivity pneumonitis supported by low-dose CT findings.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease resulting from an immune-mediated response in susceptible and sensitized individuals to various inhaled antigens in the environment. Imaging diagnosis is usually based on high-resolution CT findings. Here, we present a 49-year-old man with a history of diffuse large B-cell lymphoma presented with fever and occasional cough. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed diffuse FDG uptake in the bilateral lungs. Expiratory low-dose CT simultaneously performed in PET scanning revealed centrilobular nodules and air trapping in ground glass opacities (GGO). Our imaging diagnosis was acute hypersensitivity pneumonitis (HP). Based on the results of his clinical course, blood laboratory tests, and bronchoscopy, he was diagnosed with acute HP. Diffuse pulmonary FDG uptake can be seen in the patients with acute HP. In addition, expiratory low-dose CT findings of centrilobular nodules and air trapping in GGO may be helpful for accurate diagnosis of acute HP.

Satisfied quantitative value can be acquired by short-time bone SPECT/CT using a whole-body cadmium-zinc-telluride gamma camera.

The aim of this study was to evaluate the quantitative values of short-time scan (STS) of metastatic lesions compared with a standard scan (SS) when acquired by whole-body bone SPECT/CT with cadmium-zinc-telluride (CZT) detectors. We retrospectively reviewed 13 patients with bone metastases from prostate cancer, who underwent SPECT/CT performed on whole-body CZT gamma cameras. STSs were obtained using 75, 50, 25, 10, and 5% of the list-mode data for SS, respectively. Regions of interest (ROIs) were set on the increased uptake areas diagnosed as metastases. Intraclass correlation coefficients (ICCs) of standardized uptake values (SUVs) for the ROIs were calculated between the SS and each STS, and ICC ≥ 0.8 was set as a perfect correlation. Moreover, the repeatability coefficient (RC) was calculated, and RC ≤ 20% was defined as acceptable. A total of 152 metastatic lesions were included in the analysis. The ICCs between the SS vs. 75%-STS, 50%-STS, 25%-STS, 10%-STS, and 5%-STS were 0.999, 0.997, 0.994, 0.983, and 0.955, respectively. The RCs of the SS vs. 75%-STS, 50%-STS, 25%-STS, 10%-STS, and 5%-STS were 7.9, 12.4, 19.8, 30.8, and 41.3%, respectively. When evaluating the quality of CZT bone SPECT/CT acquired by a standard protocol, 25%-STS may provide adequate quantitative values.

Can the function of the tubarial glands be evaluated using [99mTc]pertechnetate SPECT/CT, [18F]FDG PET/CT, and [11C]methionine PET/CT?

BACKGROUND: The tubarial glands (TGs) are recently reported as newly found salivary gland structures that can be organs at risk predominantly localized in the tori tubarius in the nasopharynx using prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT). The aims of this study were to analyze uptake in the TGs compared with that in the other salivary glands and palatine tonsils using [99mTc]pertechnetate SPECT/CT, [18F]FDG PET/CT, and [11C]methionine PET/CT and to confirm whether these three imaging modalities are useful in evaluating the physiological function of the TGs. Twelve and 130 patients, who underwent [99mTc]pertechnetate SPECT/CT and [18F]FDG/[11C]methionine PET/CT, respectively, were retrospectively included. [99mTc]pertechnetate uptake in the tori tubarius was visually assessed and semiquantitatively compared with that in the background, parotid salivary glands (PSGs), submandibular salivary glands (SmSGs), and sublingual salivary glands (SlSGs). Correlations of [18F]FDG and [11C]methionine uptakes in the tori tubarius with those in the other three salivary glands and palatine tonsils were analyzed. RESULTS: [99mTc]pertechnetate uptake in the tori tubarius was invisible and was not significantly higher than that in the background. Both [18F]FDG and [11C]methionine uptakes in the tori tubarius were correlated with that in the palatine tonsils (r = 0.56, p < 0.0001; r = 0.48, p < 0.0001, respectively). [18F]FDG uptake in the tori tubarius was not positively correlated with that in the PSGs, SmSGs, and SlSGs (r = - 0.19, p = 0.03; r = - 0.02, p = 0.81; r = 0.12, p = 0.17, respectively). [11C]methionine uptake in the tori tubarius was correlated with that in the SmSGs and SlSGs (r = 0.24, p = 0.01; r = 0.32, p < 0.01, respectively), but not with that in the PSGs (r = 0.16, p = 0.08). CONCLUSIONS: The TGs were undetectable on [99mTc]pertechnetate SPECT/CT. Both [18F]FDG and [11C]methionine uptakes in the tori tubarius were clearly affected by that in the palatine tonsils and was little related to that in the other salivary glands. Therefore, it seems difficult to evaluate the physiological function of the TGs as salivary glands using [99mTc]pertechnetate SPECT/CT, [18F]FDG PET/CT, and [11C]methionine PET/CT imaging.

Test-retest repeatability of quantitative bone SPECT/CT.

OBJECTIVE: Technological innovations in single-photon emission computed tomography (SPECT) have enabled a more accurate quantitative evaluation of the uptake, and the standardized uptake value (SUV) can be measured as a semi-quantitative value, as in positron emission tomography. Nevertheless, the reliability of the SUV of bone SPECT has not been well established. The purpose of this study is to evaluate the test-retest repeatability of the SUV of bone SPECT/CT in clinical settings. METHODS: This prospective study recruited patients with prostate cancer planning to receive bone SPECT/CT for the evaluation of bone abnormality between August 2017 and September 2019. Bone images were acquired twice by an integrated SPECT/CT scanner (Symbia Intevo, Siemens) within a 4- to 10-day interval. The maximum SUV (SUVmax) and peak SUV (SUVpeak) were calculated for the volumes of interests on the normal bone areas, degeneration/fracture lesions, and metastatic lesions. To determine repeatability, we calculated statistical indicators, including intraclass correlation coefficient (ICC), repeatability coefficient (RC), and mean absolute percentage difference (MAPD). For the ICC, the 95% confidential interval (CI) was also calculated, and an ICC of ≥ 0.8 was defined as an almost perfect correlation. RESULTS: Twelve male patients were enrolled in the study (58-86 years; median, 71 years), and a total of 229 volumes of the interest were included in the analyses. The ICCs were 0.968 [95% CI (0.959, 0.975)] for SUVmax and 0.976 [95% CI (0.969, 0.981)] for SUVpeak. The RCs of the relative difference were 30.7% for SUVmax and 27.6% for SUVpeak, and the MAPDs (± standardized deviation) of all lesions were 12.3 ± 9.9% for SUVmax and 11.5 ± 8.3% for SUVpeak. The RCs and the MAPDs showed comparable value with the previous report regarding repeatability studies on PET. CONCLUSION: An almost perfect correlation was demonstrated by repeated SUVmax and SUVpeak measured by quantitative integrated SPECT/CT. The quantitative values could be reliable indicators in patient management.

Association of the primary tumor's SUVmax with survival after surgery for clinical stage IA esophageal cancer: a single-center retrospective study.

BACKGROUND: Compared to other esophageal cancers, clinical stage IA esophageal cancer generally has a good prognosis, although a subgroup of patients has a poor prognosis. Unfortunately, clinical diagnoses of invasion depth or lymph node metastasis are not always accurate, which make it difficult to identify patients with a high risk of postoperative recurrence using the tumor-node-metastasis staging system. Fluorodeoxyglucose-positron emission tomography may help guide the identification of malignant tumors and the evaluation of their malignant grade based on glucose metabolism. We aimed to evaluate the association between pre-operative fluorodeoxyglucose-positron emission tomography findings and the postoperative prognosis of patients with clinical stage IA esophageal cancer. METHODS: This single-center retrospective study evaluated pre-esophagectomy fluorodeoxyglucose-positron emission tomography findings from 38 patients with clinical stage IA esophageal cancer. Receiver operating characteristic curve analysis was performed to evaluate the prognostic significance of the primary tumor having low and high SUVmax values (cut-off: 3.56). RESULTS: Overall survival (log-rank p = 0.034) and progression-free survival (log-rank p = 0.008) were significantly different between the groups with low SUVmax values (n = 18) and high SUVmax values (n = 20). Furthermore, the primary tumor's SUVmax value was related to pathological vascular invasion (p = 0.045) and distant metastasis (p = 0.042). CONCLUSION: The SUVmax of the primary tumor is a predictor of postoperative survival for clinical stage IA esophageal cancer. Thus, using fluorodeoxyglucose-positron emission tomography to evaluate the primary tumor's glucose metabolism may reflect the tumor's grade and potentially compensate for inaccuracies in tumor-node-metastasis staging.

[18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer.

BACKGROUND: While [18F]fluoromisonidazole (FMISO), a representative PET tracer to detect hypoxia, is reported to be able to prospect the prognosis after treatment for various types of cancers, the relation is unclear for pancreatic cancer. The aim of this study is to assess the feasibility of [18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer. METHODS: Patients with pancreatic cancer who had been initially planned for surgery received [18F]FMISO PET/CT. Peak standardized uptake value (SUV) of the pancreatic tumor was divided by SUVpeak of the aorta, and tumor blood ratio using SUVpeak (TBRpeak) was calculated. After preoperative examination, surgeons finally decided the operability of the patients. TBRpeak was compared with hypoxia-inducible factor (HIF)-1α immunohistochemistry when the tissues were available. Furthermore, correlation of TBRpeak with the recurrence-free survival and the overall survival were evaluated by Kaplan-Meyer methods. RESULTS: We analyzed 25 patients with pancreatic adenocarcinoma (11 women and 14 men, median age, 73 years; range, 58-81 years), and observed for 39-1101 days (median, 369 days). Nine cases (36.0%) were identified as visually positive of pancreatic cancer on [18F]FMISO PET/CT images. TBRpeak of the negative cases was significantly lower than that of the positive cases (median 1.08, interquartile range (IQR) 1.02-1.15 vs median 1.50, IQR 1.25-1.73, p < 0.001), and the cutoff TBRpeak was calculated as 1.24. Five patients were finally considered inoperable. There was no significant difference in TBRpeak of inoperable and operable patients (median 1.48, IQR 1.06-1.98 vs median 1.12, IQR 1.05-1.21, p = 0.10). There was no significant difference between TBRpeak and HIF-1α expression (p = 0.22). The patients were dichotomized by the TBRpeak cutoff, and the higher group showed significantly shorter recurrence-free survival than the other (median 218 vs 441 days, p = 0.002). As for overall survival of 20 cases of operated patients, the higher TBRpeak group showed significantly shorter overall survival than the other (median survival, 415 vs > 1000 days, p = 0.04). CONCLUSIONS: [18F]FMISO PET/CT has the possibility to be a preoperative prognostic factor in patients with pancreatic cancer.

Ultrafast bone scintigraphy scan for detecting bone metastasis using a CZT whole-body gamma camera.

PURPOSE: To evaluate the feasibility of short whole-body bone scan acquisition times using a novel gamma camera with cadmium-zinc-telluride (CZT) semiconductor detectors. METHODS: We retrospectively enrolled 78 consecutive patients with prostate cancer who underwent bone scintigraphy using a whole-body gamma camera with CZT detectors. After acquisition of list-mode data with 180 s per bed position, anterior and posterior whole-body images were reconstructed using the first 5%, 10%, 25%, 50%, 75% and 100% of the list-mode data. Two experienced nuclear medicine physicians interpreted the images, and interrater agreement and the diagnostic value of the images were determined. Quantitative artificial neural network (ANN) values, bone scan indexes (BSI) and hotspot numbers (HsN) were also calculated by automated diagnostic software. RESULTS: Excellent interrater reliabilities of the visual assessments were obtained for the 100%, 75%, 50%, and 25% images (κ = 0.88, 0.88, 0.88 and 0.88, respectively). The 5% images also showed high diagnostic value (sensitivity 0.94, specificity 0.84 and accuracy 0.86). Intraclass correlation coefficients (ICC) between the 100% images and the reduced acquisition time images were evaluated in quantitative analyses, and excellent correlations were observed for ANN value in the 75% images (ICC 0.77), for BSI in all the reduced acquisition time images (75%, 50%, 25%, 10% and 5%; ICC 0.99, 0.99, 0.99, 0.96 and 0.75, respectively), and for HsN in the 75%, 50%, 25% and 10% images (ICC 0.99, 0.99, 0.98 and 0.90, respectively). CONCLUSION: Whole-body gamma cameras with CZT detectors have the potential to reduce image acquisition times and the dose of radioisotope injected for bone scans.

Correction to: Intracellular hypoxia measured by F-18 fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen-receptor positive breast (BRCR-D17-00693).

After the publication of this article [1], we noticed that in Fig. 2, the survival curve images (C and D, lower panel) were incorrect. The corrected Fig. 2 is presented below. The correction does not affect in any our results and conclusions.

Intracellular hypoxia measured by 18F-fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen receptor-positive breast cancer.

BACKGROUND: Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of 18F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer. METHODS: Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with 18F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR. RESULTS: Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-α, and interleukin 8. CONCLUSIONS: FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000006802 . Registered on 1 December 2011.

18F-Fluoroestradiol PET/CT Correctly Diagnosed 18F-FDG-Avid Inflammatory Lymph Nodes in a Patient With Estrogen Receptor-Positive Breast Cancer.

A 77-year-old woman with left breast cancer received F-FDG PET/CT for initial staging, and F-FDG-avid lymph nodes were observed in the bilateral axillae. As estrogen receptor (ER) status of primary lesion was positive, the patient also received F-fluoroestradiol (F-FES) PET/CT. Unlike primary lesion, no remarkable F-FES uptakes in the lymph nodes were observed. F-FDG uptakes in the nodes were finally interpreted as inflammation. F-FES PET that can noninvasively evaluate the ER status may have a potential to reveal the pathology of the false-positive lesion observed in F-FDG PET for patients with ER-positive breast cancer.

Quantification of osteoblastic activity in epiphyseal growth plates by quantitative bone SPECT/CT.

OBJECTIVE: Quantifying the function of the epiphyseal plate is worthwhile for the management of children with growth disorders. The aim of this retrospective study was to quantify the osteoblastic activity at the epiphyseal plate using the quantitative bone SPECT/CT. MATERIALS AND METHODS: We enrolled patients under the age of 20 years who received Tc-99m hydroxymethylene diphosphonate bone scintigraphy acquired by a quantitative SPECT/CT scanner. The images were reconstructed by ordered subset conjugate-gradient minimizer, and the uptake on the distal margin of the femur was quantified by peak standardized uptake value (SUVpeak). A public database of standard body height was used to calculate growth velocities (cm/year). RESULTS: Fifteen patients (6.9-19.7 years, 9 female, 6 male) were enrolled and a total of 25 legs were analyzed. SUVpeak in the epiphyseal plate was 18.9 ± 2.4 (average ± standard deviation) in the subjects under 15 years and decreased gradually by aging. The SUVpeak correlated significantly with the age- and sex-matched growth velocity obtained from the database (R2 = 0.83, p < 0.0001). CONCLUSION: The SUV measured by quantitative bone SPECT/CT was increased at the epiphyseal plates of children under the age of 15 years in comparison with the older group, corresponding to higher osteoblastic activity. Moreover, this study suggested a correlation between growth velocity and the SUV. Although this is a small retrospective pilot study, the objective and quantitative values measured by the quantitative bone SPECT/CT has the potential to improve the management of children with growth disorder.

Bevacizumab Induces Acute Hypoxia and Cancer Progression in Patients with Refractory Breast Cancer: Multimodal Functional Imaging and Multiplex Cytokine Analysis.

Purpose: Bevacizumab, an antibody against endothelial growth factor, is a key but controversial drug in the treatment of metastatic breast cancer. We, therefore, aimed to determine the intrinsic resistance to bevacizumab at the physiologic and molecular levels in advanced breast cancer using PET, dynamic contrast-enhanced MRI, diffuse optical spectroscopic imaging (DOSI), and multiplex cytokine assays.Experimental Design: In total, 28 patients diagnosed with advanced stage III/IV breast cancer receiving single-agent bevacizumab for 1 week followed by paclitaxel combined with bevacizumab underwent 18F-fluorodeoxyglucose (FDG)-PET, 18F-fluoromisonidazole (FMISO)-PET, and MRI at both baseline and two courses after treatment initiation. Hemodynamic measurement using DOSI and blood sample collection were performed at baseline and multiple times during the first week after the initiation of single-agent bevacizumab. We distinguished nonresponders from responders by serial FDG-PET based on their glycolytic changes to chemotherapy.Results: Nonresponders showed significantly higher hypoxic activity on FMISO-PET and less tumor shrinkage than responders. Hemodynamic parameters showed higher tumor blood volume and a remarkable decrease in the tissue oxygen level in nonresponders compared with responders after the infusion of single-agent bevacizumab. Multiplex cytokine assays revealed increased plasma levels of both proangiogenic and hypoxia-related inflammatory cytokines in nonresponders and decreased levels in responders.Conclusions: Nonresponders exhibited a higher degree of angiogenesis with more severe hypoxia than responders during bevacizumab treatment. These findings demonstrated that the addition of bevacizumab to paclitaxel treatment under hypoxic conditions could be ineffective and may result in acute hypoxia and increased cytokine secretion associated with cancer progression. Clin Cancer Res; 23(19); 5769-78. ©2017 AACR.

Skeletal standardized uptake values obtained by quantitative SPECT/CT as an osteoblastic biomarker for the discrimination of active bone metastasis in prostate cancer.

PURPOSE: To investigate the improvement of prognostication of active bone metastatic burden by discriminating bone metastases from degenerative changes in hot foci, using skeletal standardized uptake values (SUVs) by quantitative bone single photon emission tomography/computed tomography (SPECT/CT) in patients with prostate cancer. METHODS: We investigated 170 patients with prostate cancer who underwent skeletal quantitative SPECT/CT using 99mTc-methylene-diphosphonate (MDP), through conjugate gradient reconstruction with tissue zoning, attenuation, and scatter corrections applied, called as CGZAS reconstruction, in a retrospective cohort study. The maximum, peak, and average SUVs (SUVmax, SUVpeak, and SUVave, respectively) were obtained for visually normal thoracic (T; n = 100) and lumbar (L; n = 140) vertebral bodies as controls, as well as for bone metastases (n = 126) and degenerative changes (n = 114) as hot foci. They were also correlated with age, body-weight, height, biochemistry data, and extent of disease (EOD). Discrimination accuracy of the SUVs for bone metastases in hot foci was evaluated by a patient-based and lesion-based receiver-operator characteristic curve (ROC) analysis. RESULTS: The skeletal SUVmax was 7.58 ± 2.42 for T, 8.12 ± 12.24 for L, 16.73 ± 6.74 for degenerative changes, and 40.90 ± 33.46 for bone metastases. The SUVs of the bone metastasis group were significantly (p < 0.001) greater than of the other three groups. With disease extent, serum alkaline phosphatase and prostate specific antigen were increased, while SUVs for bone metastases were decreased in EOD grade 4. In ROC analyses for bone metastases by skeletal SUVs demonstrating the diagnostic accuracy of skeletal SUVs for discriminating bone metastasis from degenerative changes in hot foci, area under curves were 0.840, 0.817, and 0.845 in patient-based mode, and 0.932, 0.920, and 0.930 in lesion-based mode. CONCLUSIONS: The skeletal SUVs by 99mTc-MDP SPECT/CT for active bone metastases were greater than those for degenerative changes in patients with prostate cancer, with a feasible discrimination accuracy in the hot foci. Therefore, skeletal SUVs, especially SUVmax, in quantitative bone SPECT/CT may be helpful indices for the prognostication of bone metastatic burden, improving discrimination of active bone osteoblastic metastases in patients with prostate cancer from frequently coexisting degenerative changes.

Inter-rater variability of visual interpretation and comparison with quantitative evaluation of 11C-PiB PET amyloid images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) multicenter study.

PURPOSE: The aim of this study was to assess the inter-rater variability of the visual interpretation of 11C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR). METHODS: A total of 162 11C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria). RESULTS: Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p < 0.001), and positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. Significant positive/negative associations were observed between mcSUVR and the number of raters who evaluated as positive (ρ = 0.87, p < 0.0001) and negative (ρ = -0.85, p < 0.0001) interpretation. Cases of disagreement among raters showed generally low mcSUVR. CONCLUSIONS: Inter-rater agreement was almost perfect in 11C-PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may facilitate correct diagnosis when evaluating images of low amyloid deposition.

Impact of tissue photon attenuation in small animal cardiac PET imaging.

OBJECTIVES: Tissue photon attenuation is one of the essential artifacts requiring correction in clinical cardiac positron emission tomography (PET) imaging. However, due to small body size its impact on diagnostic accuracy in small rodents is considered to be limited or even ignorable. The present cardiac PET study compares lean and obese rats to determine the influence of tissue attenuation on quantitative assessment as well as regional tracer distribution. METHODS: A dedicated small animal PET system equipped with a 57Co rotating source for transmission was used. To assess the impact of tissue attenuation in rats with different body sizes, cardiac 18F-FDG -PET studies for Zucker diabetic fatty rats (obese rats) and Zucker lean rats (lean rats) were performed. The radiotracer activity reduction by attenuation was compared between the two groups. Regional tracer distribution calculated with and without attenuation correction was also assessed. RESULTS: The chest diameter was significantly longer in obese than in lean rats (5.6±0.3cm in obese and 4.5±0.2cm in lean rats, p<0.0001). Whereas the activity reduction by attenuation was significantly greater in obese than in lean rats (44.1±2.5% and 5.1±3.1%, p<0.0001), the regional variation of tissue attenuation among the ventricular walls was minimal in both lean (p=0.73) and obese rats (p=0.65). CONCLUSION: Attenuation correction is indispensable for accurate comparison of cardiac tracer activity between animals with different body size, whereas it can be omitted for evaluation of regional tracer distribution.