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Background The efficacy of neoadjuvant chemotherapy (NACT) correlates with patient survival in oesophageal squamous cell carcinoma (OSCC), but optimal evaluation of the treatment response based on PET-CT parameters has not been established. Methods We analysed 226 OSCC patients who underwent PET-CT before and after NACT followed by surgery. We assessed SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for the primary tumour and the number of PET-positive lymph nodes before and after NACT to predict patient survival. Results In a stepwise analysis, we defined 60%, 80%, and 80% as the optimal cut-off values for SUVmax, MTV, and TLG reduction, respectively, to distinguish responders and non-responders to NACT. In the ROC analysis, the TLG reduction rate was the best predictor of recurrence among PET-CT parameters. The TLG responders achieved significantly more favourable prognoses than non-responders (2-year progression-free survival [PFS] rate: 64.1% vs. 38.5%; P = 0.0001). TLG reduction rate (HR 2.58; 95% CI 1.16–5.73) and the number of PET-positive lymph nodes after NACT (HR 1.79; 95% CI 1.04–3.08) were significant independent prognostic factors. Conclusions TLG reduction is the best predictor of prognosis. Preoperative PET-CT evaluation of both the primary tumour and lymph nodes could accurately stratify risk in OSCC patients.

Purpose 4-Borono-2-[18F]fluoro-l-phenylalanine ([18F]FBPA) synthesized with [18F]F2, produced using the 18O(p, n)18F reaction, has been reported for increasing radioactivity. However, a dedicated system and complex procedure is required to reuse the costly [18O]O2 gas; also, the use of [18F]F2 as a labeling agent reduces the labeling rate and radiochemical purity. We developed a stable and practical method for [18F]FBPA synthesis by combining [18F]F2, produced using a [18O]O2 single-use system, and a [18F]CH3COOF labeling agent. Methods The produced [18F]F2 was optimized, and then [18F]FBPA was synthesized. For passivation of the target box, 0.5% F2 was pre-irradiated in argon. Gaseous products were discarded; the target box was filled with [18O]O2 gas, and then irradiated (first irradiation). Then, the [18O]O2 gas was discarded, 0.05–0.08% F2 in argon was fed into the target box, and it was again irradiated (second irradiation). The [18F]F2 obtained after this was passed through a CH3COONa column, converting it into the [18F]CH3COOF labeling agent, which was then used for [18F]FBPA synthesis. Results The mean amount of as-obtained [18F]F2 was 55.0 ± 3.3 GBq and that of as-obtained [18F]CH3COOF was 21.6 ± 1.4 GBq after the bombardment. The radioactivity and the radiochemical yield based on [18F]F2 of [18F]FBPA were 4.72 ± 0.34 GBq and 12.2 ± 0.1%, respectively. The radiochemical purity and molar activity were 99.3 ± 0.1% and 231 ± 22 GBq/mmol, respectively. Conclusion We developed a method for [18F]FBPA production, which is more stable and practical compared with the method using [18O]O2 gas-recycling and [18F]F2 labeling agent.

A biomarker that is useful for the detection of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in-house droplet digital PCR. Seventy-four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI], 66-92) and 100% (95% CI, 88-100), 85% (95% CI, 69-94) and 94% (95% CI, 73-100), and 93% (95% CI, 81-99) and 97% (95% CI, 84-100), respectively, for HPV16-related OPC, while those were 20% (95% CI, 1-72) and 100% (95% CI, 3-100), 0% (95% CI, 0-52) and 100% (95% CI, 3-100), and 100% (95% CI, 54-100) and 100% (95% CI, 16-100), respectively, for HPV16-related CUP. The sensitivity of ctHPV16DNA for HPV16-related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume, and HPV16 copy number per tumor genome in patients with HPV16-related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16-related OPC, while further studies are required for HPV16-related CUP. This article is protected by copyright. All rights reserved.

Borderline epithelial ovarian tumors are a distinct pathologic entity characterized by increased epithelial proliferation and nuclear atypia, but without frank stromal invasion. Borderline tumor (BT) is now considered to represent an intermediate phase in the stepwise progression from benign to malignant ovarian epithelial tumor. Since BTs commonly manifest at early stages in women of reproductive age and are associated with a good prognosis, making the correct diagnosis is important in determining whether a patient is a candidate for fertility-sparing surgery. There are six histologic BT subtypes (serous, mucinous, seromucinous, endometrioid, clear cell, and Brenner), and each has different MRI features, reflecting their unique histologic architectures. Radiologists should be aware of the MRI features that can suggest BTs. These features include a hyperintense papillary architecture with hypointense internal branching, which can be observed with serous and seromucinous BTs on T2-weighted images; aggregates of microcysts that have hypointensity on T2-weighted images and reticular enhancement on contrast-enhanced T2-weighted images, which can be seen with mucinous BTs; and moderately high signal intensity on diffusion-weighted images along with relatively high apparent diffusion coefficient values, which can be observed regardless of the histologic subtype. Nevertheless, because the imaging features of BTs overlap with those of many benign lesions (eg, cystadenoma and cystadenofibroma, decidualized endometriosis, and polypoid endometriosis) and malignant tumors (ovarian cancers and metastases), histologic confirmation is required for the final diagnosis. Special emphasis is placed on the MRI features of BTs, pathologic correlation, and the challenges related to diagnosis.

Background Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [18F]AlF-FAPI-74 is a positron emission tomography tracer with high selectivity for FAP, which has already shown high accumulation within human tumors in clinical studies. However, [18F]AlF-FAPI-74 radiosynthesis has not been optimized using an automated synthesizer. Herein, we report a one-pot and one-step automated radiosynthesis method using a multi purpose synthesizer. Results Radiosynthesis of [18F]AlF-FAPI-74 was performed using a cassette-type multi purpose synthesizer CFN-MPS200. After the recovery rate of trapped [18F]fluoride onto the anion-exchange cartridge using a small amount of eluent was investigated manually, a dedicated [18F]AlF-FAPI-74 synthesis cassette and synthesis program for one-pot and one-step fluorination was developed. The solutions for the formulation of [18F]AlF-FAPI-74 synthesized using this were evaluated to obtain stable radiochemical purity. The recovery rate of [18F]fluoride with only 300 µL of eluent ranged 90 ± 9% by introduction from the male side and elution from the female side of the cartridge. In automated synthesis, the eluted [18F]fluoride and precursor solution containing aluminum chloride were mixed; then, fluorination was performed in a one-pot and one-step process at room temperature for 5 min, followed by 15 min at 95 °C. As a result, the radioactivity of [18F]AlF-FAPI-74 was 11.3 ± 1.1 GBq at the end of synthesis from 32 to 40 GBq of [18F]fluoride, and its radiochemical yield was 37 ± 4% (n = 10). The radiochemical purity at the end of the synthesis was ≥ 97% for all formulation solutions. When the diluent was saline, the radiochemical purity markedly decreased after 4 h of synthesis. In contrast, with phosphate-buffered saline (pH 7.4) or 10 mM phosphate-buffered saline (pH 6.7) containing 100 mg of sodium ascorbate, the radiochemical purity was stable at 97%. Non-radioactive AlF-FAPI-74 and total impurities, including non-radioactive AlF-FAPI-74, were 0.3 ± 0.1 µg/mL and 2.8 ± 0.6 µg/mL. Ethanol concentration and residual DMSO were 5.5 ± 0.2% and 21 ± 6 ppm, respectively. Conclusions We established a one-pot one-step automated synthesis method using a CFN-MPS200 synthesizer that provided high radioactivity and stable radiochemical purity for possible clinical applications.

Purpose To evaluate the image quality and ability to delineate the small visceral arteries of high-resolution (HR) abdominal CT angiography (CTA) using an ultra-high-resolution computed tomography (UHR CT) scanner. Materials and methods Thirty-seven patients were enrolled who underwent abdominal CTA using a UHR CT scanner. The images were reconstructed with a matrix of 1024 × 1024 and 0.25 mm thickness for HR CTA and with a matrix of 512 × 512 and 0.5 mm thickness for normal resolution (NR) CTA. Maximum CT value, image quality, and delineation of the small arteries were compared between HR CTA and NR CTA. Results HR CTA showed significantly higher maximum CT value, higher image quality, and better delineation of the small arteries than did NR CTA (P Conclusion HR CTA using a UHR CT scanner showed higher image quality than NR CTA and enhanced the delineation of visceral arteries.

Background An optimal approach to imaging assessment of neck after chemoradiotherapy must be established to avoid unnecessary neck dissection. Methods We retrospectively examined 101 patients and compared between Response evaluation criteria in solid tumors (RECIST), PET response criteria in solid tumors (PERCIST), and positron emission tomography/computed tomography (PET/CT) qualitative assessment. Results PERCIST was superior to RECIST in positive predictive value (PPV; 47% vs. 36%), with equivalent negative predictive value (NPV; 78%). Only 3 of 15 patients with incomplete responses on either RECIST or PERCIST alone had regional treatment failure, and the combination of RECIST and PERCIST improved PPV (55%) without reducing NPV. This combination yielded the highest hazard ratio of regional treatment failure. The combination of RECIST and PET/CT qualitative assessment also improved PPV (50%). In human papillomavirus (HPV)-related oropharyngeal cancer, NPV was 100% across the imaging assessments, while PPV was poor (14%-33%). Conclusions Combining RECIST and PERCIST might optimize decision making in neck management after chemoradiotherapy. HPV status would affect the accuracy of response evaluation.

This study aimed to assess the relationship between pancreatic fibrosis measured by the extracellular volume fraction (ECV) using contrast-enhanced computed tomography (CT) and the histologic pancreatic fibrosis fraction and investigate the relationship between pancreatic fibrosis and pancreatic cancer.The study included 88 consecutive patients (48 males, 40 females; median age, 69 years; range, 17-89 years); 47 had pancreatic cancer, and 41 had other diseases. Fifty-two cases were evaluated pathologically for pancreatic fibrosis. The histologic pancreatic fibrosis fraction was quantified using image analysis software in nontumorous pancreatic tissue at the resection stump using 2-µm-thick Azan-stained slides. Two board-certified radiologists measured ECV in the pancreatic parenchyma at an estimated transection line. The correlation between histologic pancreatic fibrosis fraction and ECV was investigated, and whether the ECV value could be used as a biomarker for pancreatic cancer was investigated.The histologic pancreatic fibrosis fraction was significantly correlated with the ECV (r = 0.64, P 0.01). Pancreatic fibrosis evaluated by ECV was higher in pancreatic cancer patients than in other patients (P 0.01). On receiver-operating characteristic curve analysis, the ECV had good diagnostic accuracy for the development of pancreatic cancer (cut-off value 32.8%; sensitivity 61.0%, specificity 85.1%). ECV was identified on multivariate analysis as an independent risk factor for pancreatic cancer (odds ratio 1.16; P 0.01).Extracellular volume fraction was strongly related to the histologic pancreatic fibrosis fraction, which was independently associated with pancreatic cancer. Thus, extracellular volume fraction is an imaging biomarker that reflects the progression of pancreatic fibrosis and may potentially help predict the development of pancreatic cancer, although further investigation will be needed.

To investigate whether whole-body dynamic positron emission tomography (PET) is useful for differentiating benign and malignant lesions.In this retrospective study, data from a cohort of 146 lesions from 187 patients who consecutively underwent whole-body dynamic PET scans at our hospital for suspected lesions in the lung, lymph nodes, liver, bone, esophagus, and colon were analyzed. Patients with malignant lymphomas, accumulations 5 cm in length along the long axis of the esophagus, or lesions in the colon in which the site of accumulation moved during the imaging period were excluded. Patients were administered 3.7 MBq/kg of fluorine-18-fluorodeoxyglucose (F-18 FDG), and dynamic imaging was initiated 60 min after administration. We defined the 60-65, 65-70, 70-75, and 75-80 min time mark as the first, second, third, and fourth pass, respectively. The static image is the summed average of all the four pass images. We measured the accumulation in the mean image of the whole-body dynamic PET scan, which was arithmetically similar to the maximum standardized uptake value (SUVmax) throughout the whole-body static images obtained during 20 min of imaging (S-SUVmax). The ratio of SUVmax in the dynamic first pass(60-65 min after FDG administration) and fourth pass(75-80 min after FDG administration) was calculated as R-SUVmax.The S-SUVmax in the lung, lymph nodes, and bone did not differ significantly between the benign and malignant groups. However, there was a significant difference in R-SUVmax, which was 1 in most malignant lesions indicating an increase in accumulation during routine scan time. Significant differences were observed between benign and malignant lesions of the liver in both S-SUVmax and R-SUVmax values, with the latter being 1 in most malignant lesions.Whole-body dynamic PET for 20 min starting 1 h after FDG administration improved the accuracy of malignant lesion detection in the liver, lymph nodes, lung, and bone. The incremental improvement was small, and the FDG dynamics in the distribution of values between benign and malignant overlapped. Additional information from whole-body dynamic imaging can help detect malignant lesions in these sites without increasing patient burden or prolonging imaging time.

Background [18F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [18F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application. Results A dedicated single use cassette and synthesis program for [18F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [18F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [18F]PSMA-1007 synthesized in the cassette assembled by fluoro-elastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were Conclusions We successfully automated the production of [18F]PSMA-1007 for clinical use and optimized synthesis procedures with a CFN-MPS200 synthesizer using a silicone cassette and acetic acid salt precursor. Cassette availability will facilitate a wide spread use of [18F]PSMA-1007-PET, leading to an effective prostate cancer management.

Here, we assess the ability of metabolic tumor volume (MTV) as measured by F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG PET/CT) to evaluate neoadjuvant chemotherapy response for patients with locally advanced esophageal cancer (EC).Optimal methods to evaluate treatment response for EC patients have not yet been established. Although previous studies have reported the value of standardized uptake value (SUV), the accuracy of predicting histological response or long-term survival in EC is limited.In all, 102 EC patients without distant metastasis who underwent F-FDG PET/CT both before and after the preoperative chemotherapy series were analyzed.The median primary tumor MTV values before and after preoperative chemotherapy were 22.55 (range 0.4-183.1) and 2.75 (0-52.9), respectively, and the median MVT reduction rate was 86.5%. We found the most significant difference in survival between PET responders and nonresponders with a cut-off value of 60% MTV reduction, using a 10% stepwise cut-off analysis [2-year progression-free survival (PFS): 79.2 vs 44.4%; hazard ratio (HR) 3.397; P0.0001). With this cut-off value, histological response (P = 0.0091), tumor location (P = 0.0102), pT (P = 0.0011), and pN (P = 0.0110) were significantly associated with PET response. Univariate analysis of PFS indicated a correlation between PFS and tumor size, cT, decrease of primary lesion by CT, SUVmax reduction rate, MTV reduction rate, pT, pN, and pM. Multivariate analysis further identified pM (HR 3.063; P = 0.0279) and MTV reduction rate (HR 2.471; P = 0.0263) to be independent prognostic predictors, but not decrease of primary lesion by CT or SUVmax reduction rate.MTV change is clinically useful in predicting both long-term survival and histological response to preoperative chemotherapy in EC patients, after determining the optimal cut-off value based on survival analysis.

Background: Strong correlation has been reported between tissue water diffusivity and tissue elasticity in the liver. The purpose of this study is to explore the capability of diffusion–based virtual MR elastography (VMRE) in the characterization of liver tumors by extending beyond liver fibrosis assessments. Methods: Fifty-four patients (56 liver tumors: hepatocellular carcinoma (HCC), 31, metastases, 25) who underwent MRE, diffusion-weighted imaging (DWI) (b: 0, 800 s/mm2), and VMRE (b: 200, 1500 s/mm2) were enrolled. The MRE shear modulus (µMRE), apparent diffusion coefficient (ADC), and shifted ADC (sADC) were obtained. Virtual stiffness (µdiff) was estimated from the relationship between µMRE and sADC. A linear discriminant analysis combining VMRE and MRE to classify HCC and metastases was performed in a training cohort (thirty-two patients) to estimate a classifier (C), and evaluate its accuracy in a testing cohort (twenty-two patients). Pearson’s correlations between µMRE, sADC, and ADC were evaluated. In addition to the discriminant analysis, a receiver operating characteristic (ROC) curve was used to assess the discrimination capability between HCC and metastases. Results: The correlations between µMRE and sADC were significant for liver, HCC, and metastases (r = 0.91, 0.68, 0.71, all p &lt, 0.05). Those between µMRE and ADC were weaker and significant only for metastases (r = 0.17, 0.20, 0.55). µdiff values were not significantly different between HCC and metastases (p = 0.56). Areas under the curves (AUC) to differentiate HCC from metastases were as follows: VMRE, 0.46, MRE alone, 0.89, MRE + VMRE, 0.96. The classifier C also provided better performance than MRE alone, in terms of sensitivity (100 vs. 93.5%, respectively) and specificity (92 vs. 76%, respectively, p = 0.046). Conclusions: The correlation between sADC and µMRE was strong both in the liver and in tumors. However, VMRE alone could not classify HCC and metastases. The combination of MRE and VMRE, however, allowed discriminant performance between HCC and metastases.

Purpose: To compare the accuracy of liver fibrosis staging with MR elastography and of staging with extracellular volume fraction (fECV) analysis using contrast-enhanced CT. Methods: This retrospective study included 60 patients who underwent both MR elastography and contrast-enhanced CT before liver surgery between October 2013 and July 2020. Two radiologists independently measured liver stiffness of MR elastography and fECV of CT images. Accuracy for liver fibrosis staging was assessed using receiver operating characteristic (ROC) analysis. Correlations between liver stiffness or fECV and liver fibrosis were also evaluated by means of the Spearman rank correlation coefficient. Results: The areas under the ROC curves for MR elastography for each stage differentiation of ≥F1 (0.85, 0.82 for the two radiologists), ≥F2 (0.88, 0.89), ≥F3 (0.87, 0.86), and F4 (0.84, 0.83) were greater than those for fECV analysis with CT (0.64, p = 0.06, 0.69, p = 0.2; 0.62, p < 0.005, 0.63, p < 0.005; 0.62, p < 0.005, 0.62, p < 0.01; and 0.70, p = 0.08, 0.71, p = 0.2, respectively). The correlation coefficients between liver stiffness and liver fibrosis in A0 (0.67, 0.69 for the two radiologists), A1 (0.64, 0.66) and A2 group (0.58, 0.51) were significantly higher than those between fECV and liver fibrosis (0.28, 0.30; 0.27, 0.31; and 0.23, 0.07; p < 0.05 for all comparisons). Conclusion: MR elastography allows for more accurate liver fibrosis staging compared with fECV analysis with CT. In addition, MR elastography may be less affected than fECV analysis by the inflammatory condition.

A biomarker that is useful for the detection of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in-house droplet digital polymerase chain reaction. Seventy-four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI] = 66-92) and 100% (95% CI = 88-100), 85% (95% CI = 69-94) and 94% (95% CI = 73-100), and 93% (95% CI = 81-99) and 97% (95% CI = 84-100), respectively, for HPV16-related OPC, while those were 20% (95% CI = 1-72) and 100% (95% CI = 3-100), 0% (95% CI = 0-52) and 100% (95% CI = 3-100), and 100% (95% CI = 54-100) and 100% (95% CI = 16-100), respectively, for HPV16-related CUP. The sensitivity of ctHPV16DNA for HPV16-related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume and HPV16 copy number per tumor genome in patients with HPV16-related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16-related OPC, while further studies are required for HPV16-related CUP.

4-Borono-2-[The produced [The mean amount of as-obtained [We developed a method for [

Tumor blood flow (TBF) is related to drug delivery and hypoxia, both of which can impact the efficacy of anti-cancer therapies. Although integrin αvβ3 expression is related to tumor angiogenesis, it remains unclear whether the degree of angiogenesis affects TBF. This study aimed to evaluate the expression of integrin αvβ3 in mouse tumor models using [68Ga]Ga-DOTA-c(RGDfK) peptide positron emission tomography (PET) and immunohistochemical staining. PET studies were conducted using mouse C6 glioma models and MIA PaCa-2 (n = 6 each). The [68Ga]Ga-DOTA-c(RGDfK) peptide was injected via the tail vein (2.17 ± 0.28 MBq), and 10 min static PET scans were performed. Immunohistochemical analysis was conducted using an integrin αVβ3 antibody. [68Ga]Ga-DOTA-c(RGDfK) peptide PET revealed higher uptake of the radiotracer in C6 gliomas than in MIA PaCa-2 tumors. The mean standardized uptake value was significantly higher in C6 gliomas (0.35 ± 0.058) than in MIA PaCa-2 tumors (0.17 ± 0.045). Histological analysis revealed intense integrin αVβ3 expression in the C6 gliomas, whereas the MIA PaCa-2 tumors had low expression levels. This study showed that the expression of integrin αvβ3 can be differentiated by the [68Ga]Ga-DOTA-c(RGDfK) peptide, suggesting the potential applicability of this peptide in the evaluation of the relationship between angiogenesis and TBF.

To evaluate whether pancreatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) correlates with histological pancreatic fat fraction and its possible usefulness as a biomarker of pancreatic cancer compared with pancreatic index (PI) using computed tomography (CT number of the pancreas divided by that of the spleen).We included 55 consecutive patients (24 with pancreatic cancer and 31 controls; median age, 72 years) who preoperatively underwent MRI-PDFF using IDEAL-IQ and unenhanced CT and did not receive preoperative therapy. Histologic pancreatic fat fraction was measured in non-tumorous pancreatic tissues at the resection stump. A board-certified radiologist evaluated MRI-PDFF and PI. Correlations were evaluated among MRI-PDFF, PI, and histologic pancreatic fat fraction; the usefulness of MRI-PDFF as a predictor of pancreatic cancer was assessed.Histologic pancreatic fat fraction significantly correlated with MRI-PDFF and PI (r = 0.802 and -0.534, respectively; P 0.01). The absolute correlation coefficient was significantly higher for MRI-PDFF than for PI (P 0.01). Compared with the control group, the pancreatic cancer group had higher MRI-PDFF and histologic pancreatic fat fraction (P 0.01) but lower PI (P 0.01). In multivariate analysis, MRI-PDFF was found to be the sole independent risk factor for pancreatic cancer (odds ratio: 1.19; P 0.01).Pancreatic fat, which was associated with pancreatic cancer, could be quantified by MRI-PDFF measurement; therefore, MRI-PDFF should be considered as a promising and superior imaging biomarker for estimating the probability of pancreatic cancer than PI.

The purpose of this study was to determine if quantitative SUV-related, volumetric FDG PET parameters, and texture features (SPs, VPs, and TFs, respectively) were useful to evaluate and predict response and recurrence after chemotherapy in follicular lymphoma (FL). Pre- and posttreatment FDG PET examinations in 45 FL patients were analyzed retrospectively. In addition to SPs in the representative lesion, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated as VPs for the representative and whole-body lesions. Six TFs were calculated in the pretreatment representative lesion. Response results with reduction of SPs or VPs after treatment (Δ) were compared to the Lugano classification based on visual assessment. SPs, VPs, and Δ of them as well as TFs were also evaluated if they allow prediction of response and recurrence after chemotherapy. Quantitative assessment with SPs and VPs provided 89% and 93–96% concordant results, respectively, with Lugano classification. Among pretreatment PET parameters, low gray-level zone emphasis (LGZE) in TFs solely showed statistical significance to predict complete response. All of posttreatment and Δ of SPs and VPs were considered as the predictors of progression free survival in the univariate Cox regression analysis, but none of them was the predictor in the multivariate analysis. This study demonstrated that quantitative PET parameters were applicable to evaluate treatment response in FL. Texture analysis showed promise in predicting treatment response. Although posttreatment and Δ of PET parameters were the candidates, all of them proved to have limited value in predicting recurrence after chemotherapy.

The prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy.We retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models.Variables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike's information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0-1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0-12.2; P 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.

PET radioligands with low molar activity (MA) may underestimate the quantity of the target of interest because of competitive binding of the target with unlabeled ligand. The aim of this study was to evaluate the change in the whole-body distribution of 18F-PSMA-1007 targeting prostate-specific membrane antigen (PSMA) when solutions with different peptide concentrations are used. Methods: Mouse xenograft models of LNCaP (PSMA-positive prostate cancer) (n = 18) were prepared and divided into 3 groups according to the peptide concentration injected: a high-MA group (1,013 ± 146 GBq/μmol; n = 6), a medium-MA group (100.7 ± 23.1 GBq/μmol; n = 6), and a low-MA group (10.80 ± 2.84 GBq/μmol; n = 6). Static PET scans were performed 1 h after injection (scan duration, 10 min). SUVmean in tumor and normal organs was compared by the multiple-comparison test. Immunohistochemical staining and Western blot analysis were performed to confirm expression of PSMA in tumor, salivary gland, and kidney. Results: The low-MA group (SUVmean, 1.12 ± 0.30) showed significantly lower uptake of 18F-PSMA-1007 in tumor than did the high-MA group (1.97 ± 0.77) and the medium-MA group (1.81 ± 0.57). On the other hand, in salivary gland, both the low-MA group (SUVmean, 0.24 ± 0.04) and the medium-MA group (0.57 ± 0.08) showed significantly lower uptake than the high MA group (1.27 ± 0.28). The tumor-to-salivary gland SUVmean ratio was 1.73 ± 0.55 in the high-MA group, 3.16 ± 0.86 in the medium-MA group, and 4.78 ± 1.29 in the low-MA group. The immunohistochemical staining and Western blot analysis revealed significant overexpression of PSMA in tumor and low expression in salivary gland and kidney. Conclusion: A decrease in the MA level of the injected 18F-PSMA-1007 solution resulted in decreased uptake in tumor and, to a greater degree, in normal salivary gland. Thus, there is a possibility of minimizing the adverse effects in salivary gland by setting an appropriate MA level in PSMA-targeting therapy.

Purpose Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OPSCC) is extremely radiosensitive. Radiation therapy plus high-dose cisplatin remains the standard of care but causes long-term toxicity. Treatment deintensification approaches that reduce toxicity while maintaining survival are desirable for HPV-related OPSCC. Methods and Materials We conducted a single-arm, multicenter, phase 2 trial. Patients with newly diagnosed, biopsy-proven, American Joint Committee on Cancer (seventh edition) stage III or IV OPSCC positive for both p16 and HPV DNA were eligible. Patients with T4, N3, or T1N1 disease were excluded. Smoking history was not included in eligibility criteria. Patients received intensity modulated radiation therapy (IMRT) of 70 Gy in 35 fractions or 70.4 Gy in 32 fractions without chemotherapy. The primary endpoint was complete response or complete metabolic response 10 weeks after IMRT completion. Results Between September 13, 2013, and November 15, 2016, 39 patients were enrolled according to a 2-stage Simon design. Twenty-three patients (59%) had smoked for more than10 pack-years. Thirty-six patients (92%) had tumors genotyped as HPV16. Thirty-seven patients (95%) received full-dose radiation therapy and 35 (90%) had complete response or complete metabolic response. Median follow-up was 51 months (interquartile range, 41-63 months). One patient (3%) had regional recurrence and 3 (8%) had distant metastasis. One patient died of disease. The 2-year progression-free survival rate was 94% (95% CI, 81%-99%), and the 2-year overall survival rate was 100%. Common grade 3 adverse events during IMRT included mucositis in 10 patients (26%) and dysphagia in 7 patients (18%). No patients were dependent on a feeding tube at 1 month after IMRT completion. No grade 3 or 4 late adverse events were observed. Conclusions IMRT alone is associated with excellent response as well as reduced toxicity and could be a treatment option for carefully selected patients with locally advanced “true” HPV-related OPSCC. Further studies are warranted.

A newly developed Adaptive Image Receive (AIR) coil is designed to be more flexible to conform to the human body habitus, and may improve image quality by reducing the distance between the coil element and the imaging subject. This study evaluated the AIR coil's usefulness for liver MR imaging at 3.0 T in comparison with that of a conventional coil retrospectively.The study population comprised 50 consecutive patients, who underwent follow-up liver MR examinations with a 3.0-T MR system using both an AIR coil and a conventional coil to evaluate hepatocellular carcinoma. Three-dimensional fat-suppressed T1-weighted gradient-echo images before and after injection of an MRI contrast agent, T2-weighted single-shot fast spin-echo (SSFSE) images, and diffusion-weighted (DW) images obtained with the AIR coil were compared with corresponding images obtained with the conventional coil. One radiologist measured signal-to-noise ratios (SNRs), while two other radiologists used a 3-point scale to independently assess subjective image noise, artifacts, signal uniformity, and overall image quality.SNRs for the AIR coil were significantly higher than those for the conventional coil (P .05). Subjective image noise for the AIR coil on pre- and postcontrast T1-weighted and DW images was lower than for the conventional coil for both readers (P .05). Overall image quality on pre- and postcontrast T1-weighted and DW images for the AIR coil was better than that for the conventional coil for at least one reader (P .05).In comparison with the conventional coil, AIR coil improved SNR and image quality of liver MR imaging.

Background [18F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [18F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application. Results A dedicated single use cassette and synthesis program for [18F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [18F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [18F]PSMA-1007 synthesized in the cassette assembled by fluoro-elastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were

Written by associate editors of the Annals of Nuclear Medicine, this invited review article is intended to offer our readers a condensed global view on the high-quality research work that has been published in Europe last year. We have divided this article into five sections. The first three sections from the oncology category include “[18F]fluorodeoxyglucose (FDG) positron-emission tomography (PET) for therapy monitoring in malignant lymphoma”, “[18F]fluoromisonidazole (FMISO) PET for hypoxia”, and “lymphoscintigraphy update”. It is followed by a section on “amyloid PET for Alzheimer’s disease” using [11C]Pittsburgh Compound B (PiB) and [18F]florbetapir from the neurology category. The final section reviews three original articles in the field of “basic and translational molecular imaging” regardless of the category, which investigated new PET tracers such as L-4-borono-2-[18F]fluoro-phenylalanine (FBPA), O-(2-[18F]fluoroethyl)-L-tyrosine (FET) and 64Cu-NOTA-pertuzumab in small animals. We hope that this review article will arouse greater interest in our readers in recent European research trends in the field of nuclear medicine.

Peri- or intra-tumor lymphangiogenesis is induced in several types of cancer. However, the significance of peritumoral lymphatic vessels (LVs) in esophageal cancer (EC) remains to be clarified. This study included 162 eligible EC patients with or without neoadjuvant chemotherapy (NAC). The numbers of non-tumoral and peritumoral LVs were counted in resected specimens based on podoplanin immunostaining. The association between peritumoral LV number and clinicopathologic parameters, including tumor heterogeneity as measured by positron emission tomography, NAC response, and patient survival were analyzed. In non-NAC patients, the number of peritumoral LVs was highest in the lamina propria mucosa (LPM), followed by non-tumoral LVs in the LPM, peritumoral LVs in the submucosa (SM), and non-tumoral LVs in the SM. The patients with a low number of peritumoral LVs in the LPM versus those with a high number constituted a larger fraction of the NAC patients (67.8% vs. 50.0%; P = 0.022) and had a poorer pathologic response to NAC (grades 0–1a: 68.8% vs. 47.2%; P = 0.035), as well as greater tumor heterogeneity and worse survival (5-year overall survival: 50.6% vs. 72.8%; P = 0.0097). The number of peritumoral LVs in the LPM was identified as an independent prognostic factor with the highest hazard ratio (HR) of overall survival (HR 2.06; P = 0.0049) in the multivariate analysis. For EC patients, peritumoral LVs in the LPM layer are associated with tumor heterogeneity, response to NAC, and unfavorable survival.

Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO2 to the DMN. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15O-O2, 15O-CO gases and 15O-water PET. Quantitative CBF and CMRO2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson’s correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO2, respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO2. Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO2. Among them, 12 overlapping networks were observed between CBF and CMRO2. Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO2, indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. We estimated the functional correlations in the DMN by means of quantitative PET using 15O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO2, indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

We report the imaging findings of three ovarian dysgerminomas that coexisted with other germ cell tumors or gonadoblastomas, focusing on the distribution of tumor nests and vascular architecture, which might provide information about the pathogenesis of dysgerminomas. In a 14-year-old female with dysgerminoma and coexisting gonadoblastomas, contrast-enhanced magnetic resonance imaging (MRI) demonstrated a solid mass in the right ovary, which presented as hyperintense lobules on diffusion-weighted imaging separated by fibrovascular septa. Some small nodules were found to exist separately from the lobules (multiplicity) and to include pathological remnants of gonadoblastoma. Large tumor vessels were present at the center of the mass (central blood vessels), which were in direct contact with the ovarian veins and radiated peripherally through the fibrovascular septa. In a 35-year-old female, a mixed germ cell tumor, which was mainly composed of dysgerminoma and yolk sac tumor foci, exhibited the same vascular architecture pattern as the first dysgerminoma on contrast-enhanced computed tomography. In a 10-year-old female with a mixed germ cell tumor, contrast-enhanced MRI revealed an enlarged left ovary, which contained a large heterogeneous mass and multiple tiny nodules (multiplicity). Microscopically, the former corresponded to a yolk sac tumor, and the latter corresponded to a dysgerminoma containing remnants of gonadoblastoma. Based on these cases, the presence of tumor nest multiplicity and central blood vessels might aid the diagnosis of dysgerminoma, and these imaging findings might be indicative of the synchronous development of multiple dysgerminomas from primordial germ cells or gonadoblastomas.

Objectives The aim of this study was to evaluate the diagnostic ability of magnetic resonance imaging (MRI) in premenopausal women with G1 endometrial carcinoma. Methods Twenty-six patients underwent T2W, diffusion weighted, and dynamic contrast-enhanced 3-T MRI. The degree of myometrial invasion was pathologically classified into no invasion, shallow (3 mm or less), and more. Two radiologists assessed myometrial invasion on MRI. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values, AUC, and interobserver agreement were analyzed. Results For assessing myometrial invasion, mean accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and AUC, respectively, were as follows: 63%, 42%, 85%, 79%, 47%, and 0.75. Mean interobserver agreement was fair (k = 0.36). Shallow invasions were underestimated as no invasion on MRI in all 6 cases. Conclusions Magnetic resonance imaging produced false-negative result on half of patients. The misjudgments tended to happen in patients with shallow invasion.

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T-MTV) or T classification would be a better predictor of laryngectomy-free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T-MTV cut-off value was determined by time-dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T-MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T-MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T-MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97-8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47-6.69; P = 0.004) compared with small T-MTV (≤28.7 mL). The T-MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three-year LFS and OS rates for patients with small versus large T-MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2-T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99-1.00). Given the excellent interobserver reliability, T-MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.

Generally, FDG-PET/CT image is acquired at the 60th minute after tracer administration. Depending on the clinical case, additional delayed scans may be useful. However, it is difficult to judge whether additional delayed scan is useful or not. The purposes of this study were creation and evaluation of educational programs to help radiological technologists to decide the usefulness of additional delayed scan of FDG-PET/CT. METHODS Educational programs consisted of the instructional materials and the judgment test of clinical cases. The instructional materials provided the valuable findings for differentiation between uptake in the wall of the colon and colon content, distinction between uptake in the lymph node and urinary tract, and evaluation of malignancy. The judgment test of clinical cases consisted of 10 cases selected by a nuclear medicine physician (for 5 of that cases additional delayed scan was decided to be useful). Five experienced technologists and five inexperienced technologists scored the volubility of additional delayed scan pre- and post-training using the instructional materials (the full marks of score is 5). RESULTS After the educational programs using the instructional materials, the score was improved with the significant difference in both experienced (pre: 3.6±1.4, post: 4.0±1.2) and inexperienced (pre: 2.8±1.5, post: 3.7±1.5) groups (p

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years.The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2017, to all nuclear medicine institutes. The total numbers for the year 2017 were then estimated.A total of 1132 institutes responded to the survey, including 351 PET centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1332 in total, with 7.0% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 88.2 and 23.6%, respectively. The number of single-photon tracer studies in 2017 was 1.08 million which means a decrease in 5.7% in 5 years and 23.6% in 10 years. All but neurotransmitter system, sentinel lymph node, and liver scintigraphy decreased. Bone scintigraphy was a leading examination (32.3%), followed by myocardial scintigraphy (24.1%) and cerebral perfusion study (18.0%) in order. SPECT studies showed an increase from 47.2% to 63.5%. PET centers have also increased from 295 to 389, as compared to the last survey. The 112 PET centers have installed one or two in-house cyclotrons. PET studies showed 24.5% increase in 5 years, with oncology accounting for 88.9%.Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study and radionuclide targeted therapy have steadily increased.