Annals of Nuclear Medicine (v.32, #4)

Role of PET/MRI in oral cavity and oropharyngeal cancers based on the 8th edition of the AJCC cancer staging system: a pictorial essay by Tetsuya Tsujikawa; Norihiko Narita; Masafumi Kanno; Tetsuji Takabayashi; Shigeharu Fujieda; Hidehiko Okazawa (239-249).
The American Joint Committee on Cancer (AJCC) released the 8th edition of the AJCC cancer staging manual in 2017 that includes significant modifications from the 7th edition in the sections on oral cavity cancer (OCC) and oropharyngeal cancer (OPC). These highlights comprise the incorporation of the depth of invasion and exclusion of extrinsic tongue muscle involvement in the T staging of OCC, the separation of OPC staging based on the high-risk human papilloma virus status, and the inclusion of extranodal extension in N staging. The recent introduction of integrated positron emission tomography and magnetic resonance imaging (PET/MRI) with 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) has demonstrated the advantages of simultaneous PET and MR imaging with higher soft-tissue contrast, multiplanar image acquisition, and functional imaging capability. This pictorial essay discusses the role of 18F-FDG PET/MRI in the diagnosis of OCC and OPC based on the new cancer staging system.
Keywords: 8th edition of the AJCC cancer staging system; Oral cavity cancer; Oropharyngeal cancer; HPV; 18F-FDG PET/MRI

Biochemical and pathologic factors affecting technetium-99m-methoxyisobutylisonitrile imaging results in patients with primary hyperparathyroidism by Aysenur Ozderya; Sule Temizkan; Aylin Ege Gul; Sule Ozugur; Kenan Cetin; Kadriye Aydin (250-255).
Technetium 99 m methoxyisobutylisonitrile (Tc-99m MIBI) scintigraphy represents the most commonly utilized imaging modality for the detection of the diseased gland in patients with primary hyperparathyroidism (PHPT). In this study, we aimed to identify potential biological factors with an impact on MIBI sensitivity.A total of 147 patients with surgically confirmed parathyroid adenomas were assessed retrospectively. Data including medical history, biochemical and hormonal measurements, cervical US, Tc-99m MIBI scans as well as pathology reports were retrieved and recorded.Of the 147 patients, there were a total of 77, 39, and 31 cases with a positive, negative, and suspicious parathyroid adenoma on Tc-99m MIBI scan, respectively. Serum calcium (Ca), parathyroid hormone (PTH) and 25 (OH) D levels were comparable among MIBI positive and negative patients [Ca: 11.5 ± 0.9 vs 11.3 ± 0.9 mg/dL (P = 0.42); PTH: 216 (146–347) vs 194 (140–317) pg/mL (P = 0.45); 25(OH)D: 8.4 (5.7–18.2) vs 10.0 (4.7–23.3) ng/mL (P = 0.64), respectively]. P-glycoprotein (P-gp) staining was negative in both groups. Also, pathological examination of tissue preparations revealed no difference in terms of the volume of the adenomas, incidence of cystic adenomas, cell-type dominance (oxyphilic cell), percent fat, and Ki-67 ratio in MIBI positive and negative groups. The rate of hyalinization was 13% in MIBI positive and 28% in MIBI negative subjects, the difference being statistically significant (P = 0.04).Presence of hyalinization in parathyroid adenomas was found to be negatively correlated with MIBI scan results.
Keywords: Tc-99m MIBI; Parathyroid adenoma; P-glycoprotein; Ki-67 ratio

18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging by Ryuichi Nishii; Tatsuya Higashi; Shinya Kagawa; Chio Okuyama; Yoshihiko Kishibe; Masaaki Takahashi; Tomoko Okina; Norio Suzuki; Hiroshi Hasegawa; Yasuhiro Nagahama; Koichi Ishizu; Naoya Oishi; Hiroyuki Kimura; Hiroyuki Watanabe; Masahiro Ono; Hideo Saji; Hiroshi Yamauchi (256-263).
Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (18F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that 18F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, https://doi.org/10.1007/s12149-018-1236-1, 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18F-FPYBF-2 in normal healthy volunteers as a first-in-man study.Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range 25–56) were included and underwent 18F-FPYBF-2 PET/CT study for the evaluation of radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body (chest and abdomen) was performed at 0–10 min and a 15-min whole-body static scan was performed six times after the injection of 18F-FPYBF-2. After reconstructing PET and CT image data, individual organ time–activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans. The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses.Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18F-FPYBF-2. High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48 ± 1.25 µSv/MBq. The higher absorbed doses were estimated for the liver (28.98 ± 12.49 and 36.21 ± 15.64 µGy/MBq), the brain (20.93 ± 4.56 and 23.05 ± 5.03µ Gy/MBq), the osteogenic cells (9.67 ± 1.67 and 10.29 ± 1.70 µGy/MBq), the small intestines (9.12 ± 2.61 and 11.12 ± 3.15 µGy/MBq), and the kidneys (7.81 ± 2.62 and 8.71 ± 2.90 µGy/MBq) for male and female, respectively.The ED for the adult dosimetric model was similar to those of other agents used for amyloid PET imaging. The diagnostic dosage of 185–370 MBq of 18F-FPYBF-2 was considered to be acceptable for administration in patients as a diagnostic tool for the evaluation of AD.
Keywords: Alzheimer disease; Amyloid imaging; Normal healthy volunteers; Positron emission tomography; Biodistributtion; Radiation dosimetry; OLINDA/EXM

Prognostic implications of 62Cu-diacetyl-bis (N 4-methylthiosemicarbazone) PET/CT in patients with glioma by Akira Toriihara; Makoto Ohtake; Kensuke Tateishi; Ayako Hino-Shishikura; Tomohiro Yoneyama; Yoshio Kitazume; Tomio Inoue; Nobutaka Kawahara; Ukihide Tateishi (264-271).
The potential of positron emission tomography/computed tomography using 62Cu-diacetyl-bis (N 4-methylthiosemicarbazone) (62Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG).56 patients with glioma of World Health Organization grade 2–4 were enrolled. All participants had undergone both 62Cu-ATSM PET/CT and 18F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox’s proportional hazards model.Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using 62Cu-ATSM PET/CT showed significant difference of progression-free survival (p < 0.05). 62Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18F-FDG PET/CT.
Keywords: 62Cu-ATSM PET/CT; 18F-FDG PET/CT; Glioma; Tumor progression; Survival

The feasibility of 18F-FES and 18F-FDG microPET/CT for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer by Shuai Liu; Bingxin Gu; Jianping Zhang; Yongping Zhang; Xiaoping Xu; Huiyu Yuan; Yingjian Zhang; Zhongyi Yang (272-280).
Our study aimed to investigate the feasibility of PET/CT for monitoring the influence of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer.Docetaxel-insensitive ERα+ breast cancer cells (DIS-ZR751) were established, identified and cultured. ERα expression, toxicity and viability of DIS-ZR751 were analyzed before and after treatment in vitro. DIS-ZR751-bearing nude mice were randomly divided into four groups according to different treatments: blank (DIS-ZR751), docetaxel (DIS-ZR751+DOC), fulvestrant (DIS-ZR751+FUL), and combination treatment (DIS-ZR751+DOC+FUL). 18F-FES and 18F-FDG microPECT/CT scans were performed before and 7, 14 days after treatment. Absolute %ID/gmax was calculated.ERα expression level and growth rate of DIS-ZR751 were higher than control group and decreased dramatically after docetaxel and fulvestrant combination treatment. 18F-FES and 18F-FDG PET/CT imaging in vivo revealed that ERα expression in DIS-ZR751 treated with fulvestrant, and tumor activity in DIS-ZR751 treated with combination drugs decreased as early as 7 days after treatment. 18F-FES and 18F-FDG PET/CT were feasible for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulation of ERα in ERα+ breast cancer noninvasively.
Keywords: 18F-FES; 18F-FDG; Estrogen receptor alpha; Fulvestrant; Docetaxel insensitivity

Comparison of choline influx from dynamic 18F-Choline PET/CT and clinicopathological parameters in prostate cancer initial assessment by Xavier Palard-Novello; Anne-Lise Blin; David Bourhis; Etienne Garin; Pierre-Yves Salaün; Anne Devillers; Solène Querellou; Patrick Bourguet; Florence Le Jeune; Hervé Saint-Jalmes (281-287).
The aim of the study was to compare the kinetic analysis of 18F-labeled choline (FCH) uptake with static analysis and clinicopathological parameters in patients with newly diagnosed prostate cancer (PC).Sixty-one patients were included. PSA was performed few days before FCH PET/CT. Gleason scoring (GS) was collected from systematic sextant biopsies. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition (from 0 to10 min post-injection) and late whole-body acquisition (60 min post-injection). PC volume of interest was drawn using an adaptative thresholding (40% of the maximal uptake) on the late acquisition and projected onto an early static frame of 10 min and each of the 20 reconstructed frames of 30 s. Kinetic analysis was performed using an imaging-derived plasma input function. Early kinetic parameter (K1 as influx) and static parameters (early SUVmean, late SUVmean, and retention index) were extracted and compared to clinicopathological parameters.K1 was significantly, but moderately correlated with early SUVmean (r = 0.57, p < 0.001) and late SUVmean (r = 0.43, p < 0.001). K1, early SUVmean, and late SUVmean were moderately correlated with PSA level (respectively, r = 0.36, p = 0.004; r = 0.67, p < 0.001; r = 0.51, p < 0.001). Concerning GS, K1 was higher for patients with GS ≥ 4 + 3 than for patients with GS < 4 + 3 (median value 0.409 vs 0.272 min− 1, p < 0.001). No significant difference was observed for static parameters.FCH influx index K1 seems to be related to GS and could be a non-invasive tool to gain further information concerning tumor aggressiveness.
Keywords: 18F-Choline; Positron emission tomography; Prostate cancer; Kinetic analysis

Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count by Sunao Mizumura; Kazuhiro Nishikawa; Akihiro Murata; Kosei Yoshimura; Nobutomo Ishii; Tadashi Kokubo; Miyako Morooka; Akiko Kajiyama; Atsuro Terahara (288-296).
In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement.We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient’s magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method.The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD.The SBR calculated using the threshold method was highly correlated with the MRI–SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.
Keywords: 123I-FP-CIT; Dopamine transporter SPECT; Southamptom method; Threshold; Cerebrospinal fluid; Striatum binding ratio

68Ga-DOTATATE PET–CT imaging in carotid body paragangliomas by Duygu Has Şimşek; Yasemin Şanlı; Serkan Kuyumcu; Bora Başaran; Ayşe Mudun (297-301).
The aim of this study was to present our experience in the baseline evaluation of carotid body paragangliomas (CBP) with 68Ga-DOTATATE PET–CT.Five patients (4F, 1M; age 24–73 years) with CBPs who underwent 68Ga-DOTATATE PET–CT scan before the treatment were evaluated retrospectively. PET–CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUVmax).All patients had unilateral CBP lesion, showed intense 68Ga-DOTATATE uptake in PET–CT. Additionally, 68Ga-DOTATATE avid lesions were found in two patients. One of them had focal intense uptake in thyroid gland and frontal cerebrum. The other one had intense uptake in bone and adrenal mass. Four patients were operated for unilateral primary CBP. Last patient was treated with peptide receptor radionuclide therapy (177Lu-DOTATATE) for both metastatic pheochromocytoma and CBP. 68Ga-DOTATATE PET–CT is a valuable imaging modality for staging of CBPs, detecting unknown lesions and changing the management of patients. It is also useful in demonstrating expression of SSTRs for PRRT opportunity.
Keywords: Carotid body paragangliomas; 68Ga-DOTATATE; PET–CT