Metabolic Tumor Volume as Significant Predictor for Chemotherapy Containing PD-L1 Blocker in Extensive Stage Small Cell Lung Cancer.

BACKGROUND/AIM: Chemo-immunotherapy, including the programmed death ligand 1 (PD-L1) antibody, is an effective treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, no biomarker has been established for the prediction of chemo-immunotherapy. Therefore, we investigated the potential of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) as a predictive marker. PATIENTS AND METHODS: Forty-six patients with ES-SCLC who received 18F-FDG-PET immediately before combined platinum-based chemotherapy with PD-L1 blockade as a first-line treatment were eligible, and the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG uptake were evaluated. RESULTS: PD-L1 and tumor infiltrative lymphocytes (TILs) were immunohistochemically analyzed in 36 of the 46 patients. A high MTV was significantly associated with poor performance status and low albumin levels, and there was a significant association between low albumin and high TLG. Univariate analysis identified sex, Brinkman index, and MTV as significant predictors of progression-free survival (PFS), and sex, SUVmax, MTV, and TLG as significant factors of overall survival (OS). Multivariate analysis revealed that sex, Brinkman index, and MTV were independent prognostic factors for PFS, and sex, SUVmax, MTV, and TLG were significant predictors of OS. SUVmax was significantly higher in patients with positive PD-L1 expression than in those with negative expression but was not significantly different between positive and negative TILs. Moreover, the levels of MTV and TLG were not closely associated with the levels of PD-L1 and TILs. CONCLUSION: MTV or TLG metabolic tumor activity is suitable for the prediction of chemo-immunotherapy outcomes in patients with ES-SCLC.

Clinical impact of inflammatory and nutrition index based on metabolic tumor activity in non­small cell lung cancer treated with immunotherapy.

The aim of the present study was to explore the relationship between tumor metabolic glycolysis and inflammatory or nutritional status in patients with advanced non-small cell lung cancer (NSCLC) who received programmed death-1 (PD-1) blockade. A total of 186 patients were registered in the present study. All of patients underwent 18F-FDG PET imaging before initial PD-1 blockade, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed as indicators of 18F-FDG uptake. As inflammatory and nutritional index, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ration (PLR), systemic immune inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI) and Glasgow prognostic score (GPS) were evaluated based on previous assessment. 18F-FDG uptake by MTV and TLG significantly correlated with the scores of NLR, PLR, SII, PNI and ALI, in addition to the level of albumin, lactate dehydrogenase, C-reactive protein, white blood cells, neutrophils, lymphocytes and body mass index. The count of NLR, PLR and SII was significantly higher in patients with <1 year overall survival (OS) compared with in those with ≥1 year OS, and that of PNI and ALI was significantly lower in those with <1 year OS compared with those with ≥1 year OS. High MTV under the high PLR, SII and low ALI were identified as significant factors for predicting the decreased PFS and OS after PD-1 blockade in a first-line setting. In second or more lines, high MTV was identified as a significant prognostic predictor regardless of the levels of PLR, SII, ALI and GPS. In conclusion, metabolic tumor glycolysis determined by MTV was identified as a predictor for the outcome of PD-1 blockade under the high inflammatory and low nutritional conditions, in particular, when treated with a first-line PD-1 blockade. A high MTV under high PLR and SII and low ALI in the first-line setting could be more predictive of ICI treatment than other combinations.

Comparative analysis of different response criteria at early phase after PD-1 blockade in non-small lung cancer.

PURPOSE: To compare different response criteria using computed tomography (CT) and positron emission tomography (PET) in measuring response and survival in the early phase after programmed death-1 (PD-1) blockade monotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 54 patients with advanced NSCLC who had 2-deoxy-2-[fluorine-18]-fluoro-D-glucose PET or CT at baseline, and 4 and 9 weeks after PD-1 blockade, were registered. Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), the immune-modified RECIST (irRECIST), the PET Response Criteria in Solid Tumors (PERCIST), the immune-modified PERCIST (iPERCIST), and the European Organization for Research and Treatment of Cancer (EORTC) criteria for dichotomous groups, such as responders vs. non-responders and controlled vs. uncontrolled diseases. Cohen's κ was used to evaluate the concordance among the different criteria. RESULTS: The concordance between CT and PET response criteria was fair or slight for responders vs. non-responders, but the agreement between iPERCIST and irRECIST was moderate for controlled vs. uncontrolled diseases. The agreement between EORTC and PERCIST or iPERCIST in detecting responders was higher in the application of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than in the standardized uptake value corrected for lean body mass (SUL)peak. To distinguish controlled from uncontrolled disease, RECIST, irRECIST, and PET criteria (PERCIST, iPERCIST, and EORTC) defined by MTV or TLG were found to be significant predictors of progression-free survival. To distinguish responders from non-responders, iPERCIST by SULpeak or EORTC by TLG were identified as significant indicators. The EORTC criteria using TLG for the detection of responders or uncontrolled diseases had a significantly higher predictive value for response assessment. CONCLUSIONS: The EORTC criteria based on TLG for the early detection of responders and uncontrolled disease were effective as a response assessment at 4 weeks after the PD-1 blockade. When SULpeak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect.

Alteration of chronic inflammatory status by transarterial embolization in frozen shoulder evaluated by fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography.

BACKGROUND: Frozen shoulder (FS) is speculated to have an inflammatory etiology. On angiography, abnormal angiogenesis is observed around the affected shoulder, suggesting a possible source of inflammation and pain. The effectiveness and safety of transarterial embolization (TAE) targeting abnormally proliferating blood vessels have been reported. This study investigated changes in chronic inflammatory and hypoxic status before and after TAE in FS by [18F]-fluoro-2-deoxyglucose (FDG) positron-emission tomography/computed tomography as a possible mechanism of the therapeutic response to TAE. METHODS: Fifteen patients with unilateral FS, persistent for more than 6 months, who were refractory to conservative treatments, underwent TAE using the temporary embolic agent imipenem/cilastatin. Patients underwent positron-emission tomography/computed tomography with FDG (as a biomarker of inflammation) before and 8 weeks after TAE. Regional uptake was evaluated by the maximum standardized uptake value. The lesion-side-to-(contralateral-) normal-side uptake ratio was also calculated. Pain and functional scales, range-of-motion, and laboratory tests, including white blood cell, C-reactive protein, interleukin 6, vascular endothelial growth factor, and tumor necrosis factor α were evaluated. RESULTS: On FDG-PET, the average maximum standardized uptake value of the lesion-side was significantly greater than that of the normal-side (maximum standardized uptake value before TAE: 3.11 ± 1.25 vs 1.95 ± 1.15, P = .0001; 8-weeks post-TAE: 2.36 ± 0.74 vs 1.78 ± 0.69, P = .0002). The mean lesion-side-to-(contralateral-) normal-side uptake ratios before TAE (1.71 ± 0.60) decreased after TAE (1.37 ± 0.29, P = .011). The decrease of FDG uptake (-21.1 ± 12.2%) showed a significant correlation with the change in the pain scale score (r = -0.56, P = .039) and extension score (r = -0.59, P = .026). CONCLUSION: Chronic inflammation in FS, as demonstrated by FDG uptake, was decreased after TAE. Thus, chronic inflammation is likely to be an underlying mechanism that should be targeted for symptomatic improvement of frozen shoulder.

Imaging of Heart Type Fatty Acid Binding Protein Under Acute Reperfusion Ischemia Using Radio-labeled Antibody in Rat Heart Model.

Purpose: Heart-type fatty acid binding protein (H-FABP) is primary transporter of free fatty acid and plays an important role in myocardial metabolism, which is characterized by high specificity and rapid appearance under ischemic condition. The objective of this study was to clarify the usefulness of imaging study of targeting H-FABP appearance using radio-labeled antibody, and correlation with myocardial fatty acid metabolism and perfusion in acute reperfusion ischemia. Method: Wistar rats were allotted to sham-operated control group (sham; n=4), ischemia non-reperfused group (IG; n=5), and ischemia-reperfusion group (RG; n=5). Ligation of left coronary artery (LCA) was performed for IG and RG. 20 min of ischemia was followed by 60min of reperfusion for RG. 125I labeled anti H-FABP antibody (anti H-FABP), BMIPP and 99mTc-sestamibi (MIBI) was injected intravenously. Multi-tracer digital autoradiogram was performed using µ-imager®. The ratio of radioactivity in LCA related (culprit) area to the inferior (remote) area (target uptake ratio=TUR) was generated. Results: In sham group, no visually detectable accumulation was observed for the anti H-FABP image, and TURMIBI and TURBMIPP were equivalent to 1. In IG, TURMIBI and TURBMIPP were remarkably low (0.12±0.01, 0.24±0.07). In RG, TURMIBI was significantly lower (0.20±0.03, p<0.05 vs. other groups). However, TURBMIPP was significantly higher (2.78±1.28, p<0.05) compared to the sham and IG, whereas anti H-FABP showed markedly higher ratio in the reperfused area compared to the sham and IG (3.43±0.73 vs. 0.31±0.13 and 1.09±0.07 for IG and sham; p<0.05, and <0.01, respectively). Conclusion: Anti H-FABP accumulated specifically in reperfused area under acute ischemia, and it accorded to the area where fatty acid metabolism was activated. This study has shown the future potential for clinical application in vivo imaging of acute coronary syndrome.

Prognostic Potential of Metabolic Activity on 18 F-FDG Accumulation in Advanced NSCLC Receiving Combining Chemotherapy Plus PD-1 Blockade.

Combined chemotherapy plus programmed death-1 (PD-1) blockade is an established treatment against patients with advanced non-small cell lung cancer (NSCLC). However, a promising predictor besides programmed death ligand-1 expression remains uncertain. We examined the prognostic significance of baseline 18 F-FDG-positron emission tomography for predicting first-line combined chemotherapy plus PD-1 blockade in NSCLC patients. Forty-five patients with advanced NSCLC who received 18 F-FDG-positron emission tomography immediately before combined platinum-based chemotherapy with PD-1 blockade as first-line setting were eligible for this study, and assessment of maximum of standard uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18 F-FDG uptake was performed. The objective response rate, median progression-free survival, and overall survival were 51.2%, 206 days, and 681 days, respectively. High SUV max , TLG, and MTV significantly correlated with age and performance status (PS), C-reactive protein (CRP), and PS, CRP, albumin, and baseline tumor size, respectively. Univariate analysis identified albumin, TLG and MTV as significant predictors of progression-free survival, and CRP, albumin, TLG and MTV as significant factors for predicting overall survival. High TLG was confirmed as an independent factor associated with poor prognosis in multivariate analysis. In particular, TLG is identified as the most powerful predictor in patients with good PS, adenocarcinoma, programmed death ligand-1≥1%, and low baseline tumor size. The tumor metabolic volume by MTV and TLG at pretreatment was clarified as a significant predictor for combined chemotherapy with PD-1 blockade, but not maximal glycolytic level by SUV max .

Prospective assessment using 18F-FDG PET/CT as a novel predictor for early response to PD-1 blockade in non-small-cell lung cancer.

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SULmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SULmax, 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade.

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.

Visual Assessment of 18F-FDG Uptake on PET to Predict Survival Benefit to PD-1 Blockade in Non-Small Cell Lung Cancer.

BACKGROUND: Programmed death 1 (PD-1) blockade is a standard treatment for patients with metastatic non-small cell lung cancer (NSCLC). Approximately 20% patients receiving PD-1 blockade monotherapy can survive for more than 5 years. However, there are limited data on the optimal biomarkers for predicting long-term outcomes. Therefore, this study aimed to evaluate the prognostic significance of 18F-FDG uptake in patients with NSCLC responding to PD-1 blockade. PATIENTS AND METHODS: Thirty-eight patients with advanced NSCLC who underwent 18F-FDG PET after confirmation of clinical response to PD-1 blockade monotherapy were retrospectively included in this study. Visual assessment using a 5-point scale score according to 18F-FDG uptake was performed, and the 18F-FDG uptake cutoff score for prolonged response to PD-1 blockade was defined as 3 (low score: 1, 2, or 3 and high score: 4 or 5). RESULTS: A significantly greater number of patients with low scores had a performance status of 0 or 1 than patients with high scores. Among the 38 patients, 20 (53%) had a low score and 18 (47%) had a high score. Progression-free survival and overall survival were significantly longer in patients with low scores than in patients with high scores. Low 18F-FDG uptake was an independent prognostic factor for predicting favorable progression-free survival and overall survival, as confirmed by multivariate analysis. CONCLUSIONS: Tumors with lower 18F-FDG uptake on PET than normal hepatic lesions exhibit the possibility of prolonged response to PD-1 blockade. Visual assessment on PET is easy for every clinician and is understandable to confirm aggressive tumor activity.

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.

Tumor immunity is related to 18 F-FDG uptake in thymic epithelial tumor.

BACKGROUND: 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18 F-FDG) positron emission tomography (18 F-FDG-PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18 F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18 F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. METHODS: A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18 F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C, and ß2 adrenergic receptor. RESULTS: High uptakes of SUVmax , SUVmean , MTV, and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%), and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS (performance status) of 1-2, thymic carcinoma, and advanced stage, and SUVmax on 18 F-FDG uptake displayed a close association with PD-L1 and PD-L2 expressions, but not with MTV and TLG. Our analysis revealed that SUVmax was identified as being significant relationship for positive PD-L1/PD-L2 expression. GLUT1, HIF-1α, and VEGFR2 were significantly associated with the expression of PD-L1/PD-L2 from the biological viewpoint. CONCLUSION: 18 F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect the glucose metabolism and hypoxia in thymic tumor cells.

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.

Value of 18F-FDG-PET to predict PD-L1 expression and outcomes of PD-1 inhibition therapy in human cancers.

Anti-programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies are administered in varied human cancer types. The expression of PD-L1 within tumor cells has been identified as a predictive marker, although assessing its expression has benefitted only patients with non-small cell lung cancer (NSCLC) or head and neck cancer. Whereas, more than 75% of the patients with NSCLC showing partial response to PD-1 blockade therapy experienced long-term survival for more than 5-years Thus, identifying the responders to PD-1 blockade at early phase after its initiation is of clinical importance. The 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) on positron emission tomography (PET) can evaluate any tumor shrinkage by assessing the metabolic tumor volume at an earlier phase than conventional modalities such as computed tomography (CT). While several reports describe the correlation of PD-L1 expression with 18F-FDG uptake rate in the tumor cells, it remains to be delineated whether this rate determined by the glucose metabolism and hypoxia is associated with the status of immune microenvironment, including the expression of PD-L1. Moreover, details of the relationship between expression of PD-L1 and 18F-FDG uptake is still unclear. Therefore, we reviewed the clinical significance of 18F-FDG uptake on PET as a predictor of the efficacy of PD-1 blockade therapy, by correlating with the expression of PD-L1, in patients with several neoplasms.

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.

Feasibility of simultaneous 99mTc-tetrofosmin and 123I-BMIPP dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

BACKGROUND: Simultaneous dual-tracer imaging using isotopes with close photo-peaks may benefit from improved properties of cadmium-zinc-telluride (CZT)-based scanners. METHODS: Thirty patients having undergone primary percutaneous coronary intervention for acute myocardial infarction underwent single-(99mTc-tetrofosmin (TF) or 123I-BMIPP first) followed by simultaneous 99mTc-TF /123I-BMIPP dual-tracer imaging using a Discovery NM/CT 670 CZT. The values for the quantitative gated-SPECT (QGS) and the quantitative perfusion SPECT (QPS) were assessed. RESULTS: The intra-class correlation (ICC) coefficients between the single- and dual-tracer imaging were high in all the QGS and QPS data (Summed motion score: 0.95, summed thickening score: 0.94, ejection fraction: 0.98, SRS for 99mTc-TF: 0.97/ for 123I-BMIPP: 0.95). Wall motion, wall thickening and rest scores per coronary-territory-based regions were also comparable between the single- and dual imaging (ICC coefficient > 0.91). The interrater concordance in the visual analysis for the infarction and perfusion-metabolism mismatch was significant for the global and regional left ventricle (P < 0.001). CONCLUSION: The quantitative/semi-quantitative values for global and regional left-ventricular function, perfusion, and fatty acid metabolism were closely comparable between the dual-tracer imaging and the single-tracer mode. These data suggests the feasibility of the novel CZT-based scanner for the simultaneous 99mTc-TF /123I-BMIPP dual-tracer acquisitions in clinical settings.

Current status of radioligand therapy and positron-emission tomography with prostate-specific membrane antigen.

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed by prostate cancer cells. PSMA-based radioligand therapy (RLT) emerged as a promising therapeutic option for prostate cancer in the early 2000s, and has been clinically validated with great enthusiasm during these past two decades. Last year, the European Association of Nuclear Medicine (EANM) published the procedure guidelines for the safe clinical practice of Lutetium-177 (177Lu)-labelled PSMA RLT. In addition, PSMA RLT with alpha-ray-emitting radioisotopes has been also developed recently. Following the clinical use of 177Lu-PSMA RLT, PSMA-targeted positron-emission tomography (PET) with Gallium-68 (68Ga) has been performed inevitably for "theranostics" for the last decade; prostate cancer is going to be treated with PSMA-RLT based on the diagnosis by PSMA-PET. Furthermore, the diagnostic usefulness of 68Ga-PSMA PET has been documented in various diseases beyond prostate cancer more recently. Regrettably, Japan is behind European countries and the United States in this field, and has just made a belated start of their clinical trials. In this review article, we briefly overviewed the current status of PSMA RLT and PSMA PET. We hope that this topic will be a particular focus of attention for most ANM readers in Japan, and that our efforts will help to facilitate the early approval of PSMA RLT and PSMA PET by the Japanese government even if only slightly.

Tumor metabolic volume by 18F-FDG-PET as a prognostic predictor of first-line pembrolizumab for NSCLC patients with PD-L1 ≥ 50.

There is a lack of markers for predicting favorable outcomes after pembrolizumab therapy in patients with non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) expression ≥ 50%. This retrospective study examined the prognostic significance of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) uptake as a predictive marker of first-line pembrolizumab. Forty-eight patients with previously untreated NSCLC and PD-L1 expression levels ≥ 50% who underwent 18F-FDG-positron emission tomography (PET) just before administration of pembrolizumab monotherapy were eligible and underwent assessment of metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum of standardized uptake value (SUVmax) on 18F-FDG uptake. The objective response rate, median progression-free survival, and median overall survival were 51.1%, 7.1 months, and 18.6 months, respectively. In univariate survival analyses, high MTV was barely a significant prognostic predictor and was confirmed as an independent factor linked to worse outcomes in multivariate analysis, predominantly in patients with a histological diagnosis of adenocarcinoma. A high MTV was significantly associated with distant metastases (especially bone metastasis), C-reactive protein (CRP) level, and PD-L1 expression ≥ 75%. Metabolic tumor activity assessed as MTV from 18F-FDG uptake predicted the prognosis after first-line pembrolizumab treatment in patients with NSCLC and PD-L1 expression ≥ 50%, especially for adenocarcinoma.

Potential of FDG-PET as Prognostic Significance after anti-PD-1 Antibody against Patients with Previously Treated Non-Small Cell Lung Cancer.

It remains unclear whether the accumulation of 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) before the initiation of anti-programmed death-1 (PD-1) antibody can predict the outcome after its treatment. The aim of this study is to retrospectively examine the prognostic significance of 18F-FDG uptake as a predictive marker of anti-PD-1 antibody. Eighty-five patients with previously treated non-small cell lung cancer (NSCLC) who underwent 18F-FDG-positron emission tomography (PET) just before administration of nivolumab or pembrolizumab monotherapy were eligible in our study, and metabolic tumor volume (MTV), total lesion glycolysis (TLG) and the maximum of standardized under value (SUVmax) on 18F-FDG uptake were assessed. Objective response rate, median progression-free survival and median overall survival were 36.6%, 161 days and 716 days, respectively. The frequency of any immune-related adverse events was significantly higher in patients with low 18F-FDG uptake on PET than in those with high uptake. By multivariate analysis, the tumor metabolic activity by TLG and MTV was identified as an independent prognostic factor for predicting outcome after anti-PD-1 antibody therapy, but not SUVmax, predominantly in patients with adenocarcinoma. Metabolic tumor indices as TLG and MTV on 18F-FDG uptake could predict the prognosis after anti-PD-1 antibodies in patients with previously treated NSCLC.

Shortened acquisition time in simultaneous 99mTc-tetrofosmin and 123I-ß-methyl-p-iodophenyl pentadecanoic acid dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

OBJECTIVE: The use of cadmium-zinc-telluride-based scanners may increase the clinical feasibility of simultaneous dual-isotope imaging. In the current study, we sought to investigate a potential acquisition time in simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-isotope imaging using a Discovery NM/CT 670 cadmium-zinc-telluride. METHODS: Simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-isotope imaging was performed in 29 patients who had undergone primary percutaneous coronary intervention for acute myocardial infarction. Referenced images with an acquisition time of 65 s/view (16.25 min) were reframed to produce images with acquisition times of 33, 16, and 8 s/view. The values for the quantitative-gated single-photon emission computed tomography (SPECT) and the quantitative perfusion SPECT were compared. RESULTS: The quantitative-gated SPECT values for images with 33, 16, and 8 s/views showed good consistency with those for 65 s/view (the lower 95% confidence intervals for the intraclass correlation were ≥0.80). The quantitative perfusion SPECT values for Tc-tetrofosmin images with 33, 16, and 8 s/views also showed good consistency with those for 65 s/view; however, the quantitative perfusion SPECT values for I-ß-methyl-p-iodophenyl pentadecanoic acid images with an acquisition time of 8 s/view were not consistent with the reference acquisition time of 65 s/view. CONCLUSIONS: The quantitative-gated SPECT and quantitative perfusion SPECT values obtained from images with shorter acquisition times correlated with the values obtained from images with a reference acquisition time of 65 s/view; however, tracer-specific predisposition should be considered. These findings suggest that it is possible to reduce acquisition time when performing simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-tracer imaging with the novel cadmium-zinc-telluride scanner.