Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Recent topics of the clinical utility of PET/MRI in oncology and neuroscience.

Since the inline positron emission tomography (PET)/magnetic resonance imaging (MRI) system appeared in clinical, more than a decade has passed. In this article, we have reviewed recently-published articles about PET/MRI. There have been articles about staging in rectal and breast cancers by PET/MRI using fluorodeoxyglucose (FDG) with higher diagnostic performance in oncology. Assessing possible metastatic bone lesions is considered a proper target by FDG PET/MRI. Other than FDG, PET/MRI with prostate specific membrane antigen (PSMA)-targeted tracers or fibroblast activation protein inhibitor have been reported. Especially, PSMA PET/MRI has been reported to be a promising tool for determining appropriate sites in biopsy. Independent of tracers, the clinical application of artificial intelligence (AI) for images obtained by PET/MRI is one of the current topics in this field, suggesting clinical usefulness for differentiating breast lesions or grading prostate cancer. In addition, AI has been reported to be helpful for noise reduction for reconstructing images, which would be promising for reducing radiation exposure. Furthermore, PET/MRI has a clinical role in neuroscience, including localization of the epileptogenic zone. PET/MRI with new PET tracers could be useful for differentiation among neurological disorders. Clinical applications of integrated PET/MRI in various fields are expected to be reported in the future.

18F-FDG PET/CT for monitoring anti-PD-1 therapy in patients with non-small cell lung cancer using SUV harmonization of results obtained with various types of PET/CT scanners used at different centers.

OBJECTIVE: The prognostic value of treatment response in patients with non-small cell lung cancer (NSCLC) treated with immune-checkpoint inhibitors (ICIs) shown by 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) results obtained with multiple types of PET scanners using standardized uptake value (SUV) harmonization was evaluated. METHODS: Fifty-eight patients treated with ICIs who underwent 18F-FDG PET/CT examinations with nine types of PET scanners at six hospitals were enrolled. SUV harmonization of multiple PET scanner results was performed using the dedicated software packages "RAVAT" and "RC Tool for Harmonization". Tumor response was assessed by change in sum of harmonized SUVmax, according to the European Organization for Research and Treatment of Cancer (EORTC5) or the SUV of up to five lesions normalized to lean body mass, according to the PET Response Criteria in Solid Tumors (PERCIST5) and immunotherapy-modified PERCIST (imPERCIST5) criteria. The correlation between tumor response according to those three definitions and overall survival (OS) was evaluated and compared to known prognostic factors. RESULTS: One-year OS in responders and non-responders for harmonized EROTC5 was 86 and 32%, for harmonized PERCIST5 was 86 and 32%, and for harmonized imPERCIST5 was 80 and 30%, respectively (each p = 0.001). Univariate analysis showed that all response criteria remained as prognostic factors. However, there was an overlap for the categories stable metabolic disease (SMD) and progression metabolic disease (PMD) in survival curves using the PET treatment response criteria. CONCLUSION: In patients with NSCLC treated with ICIs, tumor response based on the harmonized response criteria was associated with OS. PET response criteria using harmonized metabolic parameters may be difficult to routinely employ in daily practice due to overlapping SMD and PMD, although may have a supporting role for determining prognosis.

Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors.

We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUVmax) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUVmax for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUVmax in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

Acquired Hemophilia A Presenting with Infectious Aortic Aneurysms Due to an Underlying Helicobacter cinaedi Infection.

Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. To our knowledge, this is the first report of AHA triggered by a bacterial infection; however, there may be similar cases that remain undiagnosed because this pathogen is difficult to identify. Clinicians should consider the possibility of H. cinaedi as a causative pathogen in patients presenting with a fever of unknown origin.

Usefulness of semi-automatic harmonization strategy of standardized uptake values for multicenter PET studies.

This study assessed the possibility of semi-automatic harmonization of standardized uptake values (SUVs) in multicenter studies. Phantom data were acquired using 16 PET/CT scanners (including 3 PET/CT scanners with a silicon photomultiplier detector). PET images obtained using 30-min/bed scans for optimum harmonization filter calculations and using 90-180-s/bed scans for SUV validation under clinical conditions were obtained. Time of flight and a reconstruction method with point-spread function correction were allowed. The optimal full width at half maximum of the 3D-Gaussian filter that minimizes the root mean square error with the median value of the JSNM harmonization range was calculated semi-automatically. The SUVmax and the SUVpeak of the hot spheres were measured, and the inter-scanner coefficient of variation (COV) was calculated before and after harmonization. The harmonization filter was applied to 11 of the 15 PET/CT scanners in which the SUV calibration accuracy had been verified, but not in the remaining 4 scanners. Under noiseless conditions before harmonization, the inter-scanner COVs of the SUVmax and the SUVpeak were as high as 21.57% and 12.20%, respectively, decreasing to 8.79% and 5.73% after harmonization, respectively. Harmonization brought the SUVmax of all the hot spheres to within the harmonization range. Even under clinical conditions affected by image noise, the inter-scanner COVs for the SUVmax and SUVpeak were as high as 8.83% and 5.18% after harmonization, respectively. By applying an optimal harmonization filter that is calculated semi-automatically, the harmonization of SUVs according to the JSNM strategy is possible in multicenter studies, thereby reducing inter-scanner COVs.

A pilot study on EORTC or PERCIST for the prediction of progression-free survival with nivolumab therapy in advanced or metastatic gastric cancers: A STROBE-compliant article.

ABSTRACT: Recent breakthrough results from immune checkpoint inhibitors (ICIs) have paved the way to a new era of cancer immunotherapy, and have thus led to a paradigm shift of cancer treatment. In particular, inhibition of the antiprogrammed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with ICI, including nivolumab and pembrolizumab, has been emerging as a novel treatment strategy for advanced gastric cancers. An accurate noninvasive assessment of the response to ICI is important for the management of patients with advanced or metastatic gastric cancer.To examine whether the European Organization for Research and Treatment of Cancer (EORTC) and PET Response Criteria in Solid Tumors (PERCIST) are valuable for predicting progression-free survival (PFS) in patients with advanced or metastatic gastric cancers treated with nivolumab.Six patients with advanced or metastatic gastric cancers who underwent 18F-FDG-PET/computed tomography (CT) scans before, and from 2 to 6 months after initiation of nivolumab therapy between September 2017 and August 2019, were evaluated retrospectively. The correlation between tumor progression and EORTC or PERCIST was assessed with the Fisher's exact test. The PFS was assessed with the Kaplan-Meier method.Two patients were alive without progression, and the remaining 4 patients exhibited tumor progression. Two patients without progression were classified as partial metabolic response (PMR) patients based on EORTC or PERCIST, while the other 4 patients with progression were classified as progressive metabolic disease (PMD) patients based on EORTC (P = .067), or stable metabolic disease (SMD) patients, or PMD patients based on PERCIST (P = .067).The mean and median PFS of all patients was 12.7 months (95% confidence interval [CI], 4.9-20.4 months) and 5 months (95%CI, 4.0-11.0 months). Two EORTC or PERCIST PMR patients showed significantly longer median PFS compared with 4 non-PMR patients (not reached vs 4.0 months, P = .044). Three PERCIST PMR or SMD patients also showed significantly longer median PFS compared with 3 PMD patients (not reached vs 4.0 months, P = .022). These results suggest that EORTC or PERCIST has the potential to predict PFS of patients with advanced or metastatic gastric cancers treated by nivolumab and further studies are needed to determine its value in larger study populations.

The standardized uptake value calculated from 111In-ibritumomab tiuxetan single-photon emission computed tomography/computed tomography is a useful predictor of the clinical response in patients treated by 90Y- ibritumomab tiuxetan therapy.

90Y-Ibritumomab tiuxetan (IT) therapy is a radioimmunotherapy for indolent B-cell lymphoma. Several predictors of insufficient therapeutic effects have been reported. We performed a retrospective study at a single institute to investigate whether 111In SPECT/CT can predict the therapeutic effects and grade of cytopenia due to 90Y-IT therapy. We enrolled 16 consecutive patients who underwent 90Y-IT therapy, including 15 who underwent 111In-IT SPECT/CT. After 90Y-IT therapy, there were 4 patients in complete remission in whom the lesion SUVmax on 111In-IT SPECT/CT and soluble IL-2 receptor were significantly lower than those of the other patients (P<0.05 and P<0.05, respectively). Based on the log-rank test of factors associated with the progression-free survival (PFS), ≥2 previous treatment regimens was significantly associated with a poor prognosis (P<0.05). The SUV on 111In-IT SPECT/CT may be a good predictor of the clinical response to 90Y-IT therapy.

Comparison of Cerebral Blood Flow Patterns in Patients with Phantom Bite Syndrome with Their Corresponding Clinical Features.

BACKGROUND: Phantom bite syndrome (PBS) is characterized by an uncomfortable sensation during occlusion without any evident abnormality. A recent case-control study with single-photon emission computed tomography (SPECT) using 99mTc-ethyl cysteinate dimer could not find the specific features of regional cerebral blood flow (rCBF), which might be due to the heterogeneity of PBS. We analyzed the brain images of PBS corresponding to the clinical features by studying PBS subgroups. METHODS: This study contributes to elucidating the pathophysiology of PBS by evaluating regional brain perfusion on SPECT and its clinical features. We performed SPECT using 99mTc-ethyl cysteinate dimer in 44 patients with PBS. The SPECT images were analyzed qualitatively and quantitatively. RESULTS: Asymmetrical rCBF patterns were detected, corresponding to symptom laterality. Patients with PBS with right-side symptoms showed right-side-predominant rCBF asymmetry in the parietal region and left-side-predominant rCBF asymmetry in the thalamus, and vice versa. Moreover, the analysis of the association between rCBF and patient behaviors revealed that patients who blamed their dentists for their symptoms tended to have a symmetrical rCBF pattern. CONCLUSION: Patients with PBS showed blood flow imbalance in the thalamus and parietal region corresponding to symptom laterality. There are two types of symmetrical and asymmetrical rCBF patterns in the pathophysiology of PBS despite similar clinical manifestations.

Comparison of 3 Interpretation Criteria for 68Ga-PSMA11 PET Based on Inter- and Intrareader Agreement.

PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent 68Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating 68Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue.

Physiological 68Ga-RM2 uptake in patients with biochemically recurrent prostate cancer: an atlas of semi-quantitative measurements.

AIM: 68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC. MATERIALS AND METHODS: Ninety-five participants had simultaneous PET/MRI for BCR PC and were prospectively enrolled in this study. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were measured in 24 normal anatomical structures for each participant. Three readers evaluated the images independently. Uptake in various normal tissues was classified into 4 different categories: no significant uptake if SUVmean was less than SUVmean of the aortic arch (AA); mild if SUVmean was less or equal to 2.5, but higher than SUVmean of the AA; moderate if SUVmean was higher than 2.5, but less or equal to 5; intense if SUVmean was higher than 5. RESULTS: The most intense uptake was observed in the urinary bladder, due to excretion of the radiotracer. No significant uptake was seen in the brain, salivary glands, lungs, myocardium, skeleton, muscles, and fat. Liver, spleen, and adrenal glands had mostly no significant uptake; the gastrointestinal tract had intense physiological uptake, with pancreas being the organ with the highest SUVmax measurements (average SUVmax 64.91). Mild and moderate uptake was measured in the esophagus (average SUVmax 3.99), while the stomach wall, duodenum, and rectum had mild uptake (average SUVmax 2.49, 3.42, and 3.58, respectively). CONCLUSIONS: 68Ga-RM2 has been mostly evaluated for PC detection, but it can be used for other tumors overexpressing GRPR such as breast cancer. This atlas of normal biodistribution and SUV measurements in healthy tissues will help physicians distinguish between physiological vs. pathological uptake, as well as potentially assist with planning future studies using GRPR targeting radiopharmaceuticals.

Quantitative evaluation of bone single-photon emission computed tomography using Z score analysis in patients with mandibular osteomyelitis.

OBJECTIVES: Bone scintigraphy is a functional imaging that allows early detection of bone changes, providing high sensitivity to detect osteomyelitis. The aims of this study were to develop a quantitative evaluation method for bone SPECT images of mandibular osteomyelitis, and to confirm the reliability of this method by comparing the results with the conventional subjective evaluation and other findings. METHODS: The study included 139 patients with suspected mandibular osteomyelitis who were examined by bone SPECT. Tc-99 m uptake in mandibular lesions was subjectively evaluated by comparing with that of cervical vertebrae and categorized into 5 groups. For quantitative evaluation of Tc-99 m uptake, we developed an anatomical standardization followed by Z-score analysis applied to the diagnosis of brain neurodegenerative disease. To confirm reliability, the correlation between subjective evaluation and Z-score was evaluated. Further, the relationship between the Z-score and CT findings suggestive of osteomyelitis was also evaluated. RESULTS: The correlation coefficient of voxel values was significantly improved by anatomical standardization. The Z-score of osteomyelitis was significantly correlated with subjective evaluation. It was also related to some of the CT findings (bone absorption, periosteal reaction, surrounding soft tissue inflammation). CONCLUSIONS: We developed the quantitative evaluation method of the mandible on bone SPECT images using anatomical standardization followed by Z-score analysis, and it was considered useful for evaluating mandibular osteomyelitis quantitatively.

Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors.

PURPOSE: To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET). METHODS: Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis. RESULTS: Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS. CONCLUSION: ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

18F-FPPRGD2 PET/CT in patients with metastatic renal cell cancer.

PURPOSE: The usefulness of positron emission tomography/computed tomography (PET/CT) using (18F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid peptide [PEG3-E{c(RGDyk)}2] (18F-FPPRGD2) in patients with metastatic renal cell cancer (mRCC) has not been evaluated; therefore, we were prompted to conduct this pilot study. METHODS: Seven patients with mRCC were enrolled in this prospective study. 18F-FPPRGD2 and 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT images were evaluated in a per-lesion analysis. Maximum standardized uptake value (SUVmax) and tumor-to-background ratio (T/B) were measured for all detected lesions, both before and after starting antiangiogenic therapy. RESULTS: Sixty lesions in total were detected in this cohort. SUVmax from 18F-FPPRGD2 PET/CT was lower than that from 18F-FDG PET/CT (4.4 ± 2.9 vs 7.8 ± 5.6, P < 0.001). Both SUVmax and T/B from 18F-FPPRGD2 PET/CT decreased after starting antiangiogenic therapy (SUVmax, 4.2 ± 3.2 vs 2.6 ± 1.4, P = 0.003; T/B, 3.7 ± 3.2 vs 1.5 ± 0.8, P < 0.001). Average changes in SUVmax and T/B were - 29.3 ± 23.6% and - 48.1 ± 28.3%, respectively. CONCLUSIONS: 18F-FPPRGD2 PET/CT may be an useful tool for monitoring early response to antiangiogenic therapy in patients with mRCC. These preliminary results need to be confirmed in larger cohorts.

Change of Cerebral Blood Flow After a Successful Pharmacological Treatment of Phantom Bite Syndrome: A Case Report.

BACKGROUND: "Phantom bite syndrome," a persistent complaint of an uncomfortable bite sensation with no obvious occlusal abnormal finding, recently was suggested to be related with central nervous system dysfunction. Here, we report a case of phantom bite syndrome in which the occlusal discomfort was improved with mirtazapine and aripiprazole combination parallel with regional cerebral blood flow change. CASE REPORT: A 60-year-old-female patient came to our clinic with the chief complaint of a "loosely bite" after dental treatment and various uncomfortable sensations of body sites. One year after the medication therapy, the prosthodontic retreatment was carried out successfully, and a good outcome was obtained for over 24 months so far. In addition, a subsequent change of regional cerebral blood flow was observed in single-photon emission computed tomography: the right and left asymmetry of cerebral blood flow in the frontal lobe has disappeared along with the improvement to the symptoms improvement. CONCLUSIONS: This case suggests that some central nervous system dysfunction involving dopaminergic system might be related to the pathophysiology of phantom bite syndrome.

Predicting Response to Immunotherapy by Evaluating Tumors, Lymphoid Cell-Rich Organs, and Immune-Related Adverse Events Using FDG-PET/CT.

PURPOSE: To investigate whether the evaluation of tumors, lymphoid cell-rich organs, and immune-related adverse events (IRAE) with F-FDG PET/CT can predict the efficacy and outcome of immunotherapy. METHODS: Forty patients who underwent F-FDG-PET/CT scans before and after therapy with immune checkpoint inhibitors from December 2013 to December 2016 were retrospectively enrolled (malignant melanoma, n = 21; malignant lymphoma, n = 11; renal cell carcinoma, n = 8). SUVmax of the baseline and first restaging scans were evaluated in tumors, spleen, bone marrow, thyroid and pituitary glands, and were correlated to best overall response in the first year after therapy; IRAE-affected areas were also evaluated. RESULTS: Interval change between the baseline and first restaging scans showed that patients with a clinical benefit had a significant decrease in tumor parameters (P < 0.001). All patients with an increase of SUVmax in the thyroid of more than 1.5 (n = 5) on the first restaging scan had a complete response (CR) in 1 year. Patients with CR within 1 year (n = 22) were significantly associated with a favorable long-term outcome (P = 0.002). Nine patients with IRAE findings had CR at final evaluation. Among IRAE, thyroiditis was seen significantly earlier than arthritis (P = 0.040). CONCLUSIONS: The decrease of tumor parameters at early time-point PET scans was seen in patients with immunotherapy who had clinical benefit within 1 year. PET-detectable IRAE was useful for prediction of a favorable outcome. Early development of thyroiditis may particularly represent an early response indicator to immunotherapy.

Prognostic value of metabolic tumor burden calculated using dual-time-point 18F-fluorodeoxyglucose positron emission tomography/CT in patients with oropharyngeal or hypopharyngeal cancer.

BACKGROUND: This study investigates the prognostic value of metabolic tumor burden calculated using dual-time-point 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in patients with locally advanced cancer. METHODS: This study examines 42 patients (35 men and 7 women, 38-73 years old) with locally advanced oropharyngeal or hypopharyngeal cancer who had undergone FDG-PET/CT before receiving chemoradiotherapy. Maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for the early and delayed phases. Statistical analyses included receiver operating characteristic curve, univariate and multivariate analysis. RESULTS: ΔSUVmax , both phases of MTV2.5 and TLG2.5 , early TLG40% , ΔTLG2.5 , and ΔTLG40% were significantly associated with progression-free survival (PFS). In multivariate analysis, early TLG2.5 (P = .005) was an independent prognostic factor of PFS. CONCLUSION: Not the percent change but the value calculated in the early phase in several parameters using dual-time-point FDG-PET/CT is significantly associated with the outcomes of patients with locally advanced oropharyngeal or hypopharyngeal cancer.

Semiquantitative analysis using standardized uptake value in 123I-FP-CIT SPECT/CT.

PURPOSE: To evaluate potential of a semiquantitative method using standardized uptake value (SUV) in 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) single photon emission computed tomography/computed tomography (SPECT/CT) compared with specific binding ratio (SBR). MATERIALS AND METHODS: First, we performed a phantom study to validate the accuracy of measuring SUV. 52 patients (25 male, 27 female; mean age of 75.1-year-old; 40 and 12 patients with neurodegenerative diseases with or without presynaptic dopaminergic deficits, respectively) were enrolled in a retrospective study. We measured SBR, maximum SUV, peak SUV, mean SUV, and striatum-to-background ratio of SUV (SUVratio) for striatum with lower 123I-FP-CIT uptake using commercial software. We calculated Pearson's correlation coefficient between SBR and SUV. We also calculated the sensitivity, specificity, and accuracy of each parameter for differential diagnosis. RESULTS: The phantom study revealed errors of <10% between theoretical and actual SUVs. Although there were significant correlations between SBR and all SUV-based parameters, SUVratio showed the most strong correlation with SBR (r = 0.877, p < 0.001). However, diagnostic capability of SUVratio (cutoff = 2.35) yielded to that of SBR (cutoff = 3.90) for diagnosing neurodegenerative diseases with presynaptic dopaminergic deficits (sensitivity of 85.0% vs 92.5%, specificity of 100% vs 91.7%, and accuracy of 88.5% vs 92.3%, respectively). CONCLUSION: SBR is a promising parameter to aid differential diagnosis of neurodegenerative diseases with or without presynaptic dopaminergic deficit. Although technically acceptable, SUV may not be superior to SBR when clinically applied in 123I-FP-CIT SPECT/CT.

Applying standardized uptake values in gallium-67-citrate single-photon emission computed tomography/computed tomography studies and their correlation with blood test results in representative organs.

OBJECTIVES: Recently, semiquantitative analysis using standardized uptake value (SUV) has been introduced in bone single-photon emission computed tomography/computed tomography (SPECT/CT). Our purposes were to apply SUV-based semiquantitative analytic method for gallium-67 (Ga)-citrate SPECT/CT and to evaluate correlation between SUV of physiological uptake and blood test results in representative organs. METHODS: The accuracy of semiquantitative method was validated using an National Electrical Manufacturers Association body phantom study (radioactivity ratio of sphere : background=4 : 1). Thereafter, 59 patients (34 male and 25 female; mean age, 66.9 years) who had undergone Ga-citrate SPECT/CT were retrospectively enrolled in the study. A mean SUV of physiological uptake was calculated for the following organs: the lungs, right atrium, liver, kidneys, spleen, gluteal muscles, and bone marrow. The correlation between physiological uptakes and blood test results was evaluated using Pearson's correlation coefficient. RESULTS: The phantom study revealed only 1% error between theoretical and actual SUVs in the background, suggesting the sufficient accuracy of scatter and attenuation corrections. However, a partial volume effect could not be overlooked, particularly in small spheres with a diameter of less than 28 mm. The highest mean SUV was observed in the liver (range: 0.44-4.64), followed by bone marrow (range: 0.33-3.60), spleen (range: 0.52-2.12), and kidneys (range: 0.42-1.45). There was no significant correlation between hepatic uptake and liver function, renal uptake and renal function, or bone marrow uptake and blood cell count (P>0.05). CONCLUSION: The physiological uptake in Ga-citrate SPECT/CT can be represented as SUVs, which are not significantly correlated with corresponding blood test results.