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Purpose: Deep learning (DL) has been widely used in various medical imaging analyses. Because of the difficulty in processing volume data, it is difficult to train a DL model as an end-to-end approach using PET volume as an input for various purposes including diagnostic classification. We suggest an approach employing two maximum intensity projection (MIP) images generated by whole-body FDG PET volume to employ pre-trained models based on 2-D images., Methods: As a retrospective, proof-of-concept study, 562 [ 18 F]FDG PET/CT images and clinicopathological factors of lung cancer patients were collected. MIP images of anterior and lateral views were used as inputs, and image features were extracted by a pre-trained convolutional neural network (CNN) model, ResNet-50. The relationship between the images was depicted on a parametric 2-D axes map using t-distributed stochastic neighborhood embedding (t-SNE), with clinicopathological factors., Results: A DL-based feature map extracted by two MIP images was embedded by t-SNE. According to the visualization of the t-SNE map, PET images were clustered by clinicopathological features. The representative difference between the clusters of PET patterns according to the posture of a patient was visually identified. This map showed a pattern of clustering according to various clinicopathological factors including sex as well as tumor staging., Conclusion: A 2-D image-based pre-trained model could extract image patterns of whole-body FDG PET volume by using anterior and lateral views of MIP images bypassing the direct use of 3-D PET volume that requires large datasets and resources. We suggest that this approach could be implemented as a backbone model for various applications for whole-body PET image analyses., Competing Interests: Competing InterestsJoonhyung Gil, Hongyoon Choi, Jin Chul Paeng, Gi Jeong Cheon, and Keon Wook Kang declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: In this study, we propose a deep learning (DL)-based voxel-based dosimetry method in which dose maps acquired using the multiple voxel S-value (VSV) approach were used for residual learning., Methods: Twenty-two SPECT/CT datasets from seven patients who underwent 177 Lu-DOTATATE treatment were used in this study. The dose maps generated from Monte Carlo (MC) simulations were used as the reference approach and target images for network training. The multiple VSV approach was used for residual learning and compared with dose maps generated from deep learning. The conventional 3D U-Net network was modified for residual learning. The absorbed doses in the organs were calculated as the mass-weighted average of the volume of interest (VOI)., Results: The DL approach provided a slightly more accurate estimation than the multiple-VSV approach, but the results were not statistically significant. The single-VSV approach yielded a relatively inaccurate estimation. No significant difference was noted between the multiple VSV and DL approach on the dose maps. However, this difference was prominent in the error maps. The multiple VSV and DL approach showed a similar correlation. In contrast, the multiple VSV approach underestimated doses in the low-dose range, but it accounted for the underestimation when the DL approach was applied., Conclusion: Dose estimation using the deep learning-based approach was approximately equal to that in the MC simulation. Accordingly, the proposed deep learning network is useful for accurate and fast dosimetry after radiation therapy using 177 Lu-labeled radiopharmaceuticals., Competing Interests: Competing InterestsKeon Min Kim, Min Sun Lee, Min Seok Suh, Gi Jeong Cheon, and Jae Sung Lee declare no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Prostate-specific membrane antigen (PSMA) is highly expressed in PCa, which gradually increases in high-grade tumors, metastatic tumors, and tumors nonresponsive to androgen deprivation therapy. PSMA has been a topic of interest during the past decade for both diagnostic and therapeutic targets. Radioligand therapy (RLT) utilizes the delivery of radioactive nuclides to tumors and tumor-associated targets, and it has shown better efficacy with minimal toxicity compared to other systemic cancer therapies. Nuclear medicine has faced a new turning point claiming theranosis as the core of academic identity, since new RLTs have been introduced to clinics through the official new drug development processes for approval from the Food and Drug Administration (FDA) or European Medical Agency. Recently, PSMA targeting RLT was approved by the US FDA in March 2022. This review introduces PSMA RLT focusing on ongoing clinical trials to enhance our understanding of nuclear medicine theranosis and strive for the development of new radiopharmaceuticals., Competing Interests: Competing InterestsSo Won Oh, Minseok Suh, and Gi Jeong Cheon declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: 68  Ga-DOTA-TOC uptake in the pancreas uncinate process is often found due to physiologic expression of somatostatin receptors (SSTR). We investigated the association of physiologic 68  Ga-DOTA-TOC uptake in the pancreas uncinate process with blood glucose level., Methods: 68  Ga-DOTA-TOC PET scans acquired from 44 patients (male:female = 20:24, age = 50.8 ± 14.8y [mean ± SD]) were retrospectively analyzed. The blood glucose level (BGL) was examined before 68  Ga-DOTA-TOC injection. Patients diagnosed with diabetes mellitus and patients with BGL over 200 mg/dl were excluded. 68  Ga-DOTA-TOC uptake was measured by the maximum standardized uptake values (SUVmax). Additionally, SSTR-positive volume (SV) in the pancreas uncinate process was measured with two different thresholds: by SUV cutoff of 2.5 (SV 2.5 ) and 40% of SUVmax (SV 40% ). These measurements on 68  Ga-DOTA-TOC PET were correlated with BGL., Results: The mean of SUVmax of the pancreas uncinate process was 6.51 ± 2.04. SV 2.5 was 17.81 ± 7.14 cm 3 , and SV 40% was 18.20 ± 8.83 cm 3 . A significant negative correlation was found between SUVmax of the pancreas uncinate process and BGL ( r  = -0.37, p  = 0.01). The ratio between SUVmax of the pancreas uncinate process and SUVmean of the pancreas body also showed a significance negative correlation with BGL ( r  = -0.40, p  = 0.01). SV 2.5 ( r  = 0.27, p  = 0.07) and SV 40% ( r  = -0.151, p  = 0.32) were not significantly correlated with BGL., Conclusion: Physiologic 68  Ga-DOTA-TOC uptake in the pancreas uncinate process was negatively correlated with BGL. Our results suggested that glycemia could affect physiologic uptake of 68  Ga-DOTA-TOC., Competing Interests: Competing InterestsDongkyu Oh, Hongyoon Choi, Jin Chul Paeng, Keon Wook Kang, and Gi Jeong Cheon declare no conflict of interest., (© Korean Society of Nuclear Medicine 2021.)

Rosai-Dorfman disease or sinus histiocytosis with lymphadenopathy is a rare benign histiocytic proliferative disorder of unknown etiology first described in 1969. It typically affects older females and most common presentation is with massive lymphadenopathy and nonspecific systemic symptoms; therefore, it is often confused with lymphoproliferative disorders [1, 2]. We present the case of a 69-year-old woman with nasal obstruction as only complaint. Laboratory tests showed normal leukocyte count with elevated ANC (absolute neutrophil count), normal RBC count with normal MCV (mean corpuscular volume) and MCH (mean corpuscular hemoglobin), elevated ESR (erythrocyte sedimentation rate), and normal IgG, IgA, and IgM values. Evaluation revealed a nasopharyngeal mass, which was biopsied and reported emperipolesis with positive CD68 and S-100; typical and differential findings of this disease [1, 2]. 18 F FDG PET/CT was performed to determine the extent and involvement of the disease. Considering the presence of few symptoms and no significant laboratory abnormality, treating physicians decided to start a regimen of corticosteroids (prednisolone) for a period of 4 months, after which a follow-up with 18 F FDG PET/CT will be performed., Competing Interests: Conflict of InterestVanessa Murad and Gi Jeong Cheon declare that they have no conflict of interest., (© Korean Society of Nuclear Medicine 2021.)

Purpose: The precise quantification of dopamine transporter (DAT) density on N -(3-[ 18 F]Fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography ([ 18 F]FP-CIT PET) imaging is crucial to measure the degree of striatal DAT loss in patients with parkinsonism. The quantitative analysis requires a spatial normalization process based on a template brain. Since the spatial normalization method based on a delayed-phase PET has limited performance, we suggest an early-phase PET-based method and compared its accuracy, referring to the MRI-based approach as a gold standard., Methods: A total of 39 referred patients from the movement disorder clinic who underwent dual-phase [ 18 F]FP-CIT PET and took MRI within 1 year were retrospectively analyzed. The three spatial normalization methods were applied for quantification of [ 18 F]FP-CIT PET-MRI-based anatomical normalization, PET template-based method based on delayed PET, and that based on early PET. The striatal binding ratios (BRs) were compared, and voxelwise paired t tests were implemented between different methods., Results: The early image-based normalization showed concordant patterns of putaminal [ 18 F]FP-CIT binding with an MRI-based method. The BRs of the putamen from the MRI-based approach showed higher agreement with early image- than delayed image-based method as presented by Bland-Altman plots and intraclass correlation coefficients (early image-based, 0.980; delayed image-based, 0.895). The voxelwise test exhibited a smaller volume of significantly different counts in putamen between brains processed by early image and MRI compared to that between delayed image and MRI., Conclusion: The early-phase [ 18 F]FP-CIT PET can be utilized for spatial normalization of delayed PET image when the MRI image is unavailable and presents better performance than the delayed template-based method in quantitation of putaminal binding ratio., Competing Interests: Conflict of InterestSungwoo Bae, Hongyoon Choi, Wonseok Whi, Jin Chul Paeng, Gi Jeong Cheon, Keon Wook Kang, and Dong Soo Lee declare that they have no conflict of interest., (© Korean Society of Nuclear Medicine 2020.)

Purpose: EGFR-mutation (EGFR-mt) is a major oncogenic driver mutation in lung adenocarcinoma (ADC) and is more often observed in Asian population. In lung ADC, some radiomics parameters of FDG PET have been reported to be associated with EGFR-mt. Here, the associations between EGFR-mt and PET parameters, particularly asphericity (ASP), were evaluated in Asian population., Methods: Lung ADC patients who underwent curative surgical resection as the first treatment were retrospectively enrolled. EGFR mutation was defined as exon 19 deletion and exon 21 point mutation and was evaluated using surgical specimens. On FDG PET, image parameters of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and ASP were obtained. The parameters were compared between EGFR-mt and wild type (EGFR-wt) groups, and the relationships between these PET parameters and EGFR-mt were evaluated., Results: A total of 64 patients (median age 66 years, M:F = 34:30) were included in the analysis, and 29 (45%) patients showed EGFR-mt. In EGFR-mt group, all the image parameters of SUVmax, MTV, TLG, and ASP were significantly lower than in EGFR-wt group (all adjusted P  < 0.050). In univariable logistic regression, SUVmax ( P  = 0.003) and ASP ( P  = 0.010) were significant determinants for EGFR-mt, whereas MTV was not ( P  = 0.690). Multivariate analysis revealed that SUVmax and ASP are independent determinants for EGFR-mt, regardless of inclusion of MTV in the analysis ( P  < 0.05)., Conclusion: In Asian NSCLC/ADC patients, SUVmax, MTV, and ASP on FDG PET are significantly related to EGFR mutation status. Particularly, low SUVmax and ASP are independent determinants for EGFR-mt., Competing Interests: Conflict of InterestWonseok Whi, Seunggyun Ha, Sungwoo Bae, Hongyoon Choi, Jin Chul Paeng, Gi Jeong Cheon, Keon Wook Kang, and Dong Soo Lee declare that there is no conflict of interest. There is no source of funding., (© Korean Society of Nuclear Medicine 2020.)

Purpose: Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers., Methods: Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method., Results: The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PET and a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively., Conclusion: We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers., Competing Interests: Conflict of InterestJi-Young Kim, Hoon Young Suh, Hyun Gee Ryoo, Donkyu Oh, Hongyoon Choi, Jin Chul Paeng, Gi Jeong Cheon, Keon Wook Kang, Dong Soo Lee, and for the Alzheimer’s Disease Neuroimaging Initiative declare that they have no conflict of interest., (© Korean Society of Nuclear Medicine 2019.)

Radiomics is a medical imaging analysis approach based on computer-vision. Metabolic radiomics in particular analyses the spatial distribution patterns of molecular metabolism on PET images. Measuring intratumoral heterogeneity via image is one of the main targets of radiomics research, and it aims to build a image-based model for better patient management. The workflow of radiomics using texture analysis follows these steps: 1) imaging (image acquisition and reconstruction); 2) preprocessing (segmentation & quantization); 3) quantification (texture matrix design & texture feature extraction); and 4) analysis (statistics and/or machine learning). The parameters or conditions at each of these steps are effect on the results. In statistical testing or modeling, problems such as multiple comparisons, dependence on other variables, and high dimensionality of small sample size data should be considered. Standardization of methodology and harmonization of image quality are one of the most important challenges with radiomics methodology. Even though there are current issues in radiomics methodology, it is expected that radiomics will be clinically useful in personalized medicine for oncology., Competing Interests: Seunggyun Ha, Hongyoon Choi, Jin Chul Paeng, and Gi Jeong Cheon declare no conflict of interest.This work does not contain any studies with human participants or animals performed by any of the authors. For this type of study, formal consent is not required.Not applicable.

Purpose: In malignant melanoma, recurrence is often observed in distant areas from the primary site. While FDG PET is a sensitive imaging for detecting malignant lesions, the role of FDG PET in posttreatment surveillance period has not been investigated sufficiently. The aim of this study was to evaluate the value of PET during posttreatment surveillance in melanoma., Methods: A total of 76 melanoma patients who underwent FDG PET during surveillance period after completion of the first treatment were retrospectively enrolled. PET scans were grouped according to the purpose and clinical situations, routine surveillance, or evaluating clinical suspicion. Final diagnosis of recurrence was determined by complete clinical evaluation or long-term follow-up. In each situation, the diagnostic role of FDG PET was assessed., Results: A total of 143 scans of 76 patients were analyzed: 51 for clinical suspicion and 92 for routine surveillance. In the clinical suspicion group, PET correctly diagnosed non-recurrence in 10 cases (20%). In routine surveillance group, 16 cases (17%) presented recurrence, all of which was correctly diagnosed on PET. NPV and PPV were 100% and 76%, respectively. In subgroup analysis, sensitivity and NPV were higher in the low-risk group (stages I-II A ) than in the high-risk group (stages II B -IV), while specificity and PPV were higher in the high-risk group., Conclusion: In conclusion, FDG PET is an effective diagnostic tool in posttreatment surveillance of melanoma. Even in cases without clinical suspicion, melanoma recurs in a considerable proportion of patients, which can be sensitively diagnosed on PET., Competing Interests: Hwan Hee Lee, Jin Chul Paeng, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, and Keon Wook Kang declare that they have no conflict of interest.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.The study design of the retrospective analysis and exemption of informed consent were approved by the Institutional Review Board of the Seoul National University Hospital (H-1804-008-932).

Although radioiodine has been applied in thyroid diseases including carcinoma for over 70 years, it was only in 1996 that the basic molecular mechanism of iodine uptake was identified. Iodide is actively transported into the thyroid via a membrane glycoprotein known as sodium iodide symporter (NIS). NIS mediates radioiodine uptake into thyroid normal and cancer cells. The knowledge on NIS expression has provided scientific background to the empirical management of thyroid carcinoma. Based on recent studies of the NIS gene, this paper provides current clinical applications and future studies., Competing Interests: June-Key Chung, Hyun Woo Kim, Haewon Youn, and Gi Jeong Cheon declare no conflict of interest.This article does not contain any studies with human participants or animals performed by any of the authors.

Purpose: Although 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a standard imaging modality for response evaluation in FDG-avid lymphoma, there is a controversy using FDG PET in indolent lymphoma. The purpose of this study was to investigate the effectiveness of quantitative indexes on FDG PET in response evaluation of the indolent lymphoma., Methods: Fifty-seven indolent lymphoma patients who completed chemotherapy were retrospectively enrolled. FDG PET/computed tomography (CT) scans were performed at baseline, interim, and end of treatment (EOT). Response was determined by Lugano classification, and progression-free survival (PFS) by follow-up data. Maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured in the single hottest lesion (target A) or five hottest lesions (target B). Their efficacies regarding response evaluation and PFS prediction were evaluated., Results: On EOT PET, SUV max , and MTV of both targets were well associated with visual analysis. Changes between initial and EOT PET were not significantly different between CR and non-CR groups. On interim PET, SUV max , and %ΔSUV max in both targets were significantly different between CR and non-CR groups. For prediction of PFS, most tested indexes were significant on EOT and interim PET, with SUV max being the most significant prognostic factor., Conclusion: Quantitative indexes of FDG PET are well associated with Lugano classification in indolent lymphoma. SUV max measured in the single hottest lesion can be effective in response evaluation and prognosis prediction on interim and EOT PET., Competing Interests: Hyun Joo Kim, Reeree Lee, Hongyoon Choi, Jin Chul Paeng, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, and Keon Wook Kang declare that they have no conflict of interest.All procedures followed were performed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2013.The study design of the retrospective analysis and exemption of informed consent were approved by the Institutional Review Board of the Seoul National University Hospital (H-1703-108-840). This manuscript has not been published before or is not under consideration for publication anywhere else and has been approved by all co-authors.

Purpose: 68 Ga-labeled 1,4,7,10-tetraazacyclododecane- N , N ', N ″, N ‴-tetraacetic acid-d-Phe 1 -Tyr 3 -octreotide ( 68 Ga-DOTATOC) is taken up by activated macrophages, which accumulate in active inflammatory lesions. The purpose of this study was to investigate the feasibility of 68 Ga-DOTATOC PET/CT for assessment of vulnerable plaque, by evaluating correlation between aortic uptake of 68 Ga-DOTATOC and cardiovascular risk factors., Methods: Fifty patients with neuroendocrine tumors who underwent 68 Ga-DOTATOC PET/CT were retrospectively enrolled. The uptakes in the thoracic aorta were measured by two methods: multi-sample region-of-interest (ROI) method and single volume-of-interest (VOI) method. TBR max-avg , TBR mean-avg , TBR max-VOI , and TBR mean-VOI were defined by maximum and mean target-to-background ratio (TBR) from the multi-sample ROI method and the single VOI method, respectively., Results: Framingham risk score (FRS) exhibited significant correlations with TBR max-avg and TBR mean-avg , as well as TBR max-VOI ( r  = 0.3389-0.4593, P  < 0.05 for all). TBR max-avg and TBR max-VOI were significantly higher in high FRS group than in low FRS group (1.48 ± 0.21 vs. 1.70 ± 0.17, P  < 0.001 for TBR max-avg and 1.90 ± 0.33 vs. 2.25 ± 0.36, P  = 0.002 for TBR max-VOI ). TBR exhibited high correlations between the two measuring methods ( r  = 0.9684, P  < 0.001 for TBR mean-avg and TBR mean-VOI and r  = 0.8681, P  < 0.001 for TBR max-avg and TBR max-VOI )., Conclusions: 68 Ga-DOTATOC uptake in the thoracic aorta exhibited a significant correlation with cardiovascular risk factors, which suggests the feasibility of 68 Ga-DOTATOC PET for vulnerable plaque imaging, with a simple measurement of the single VOI method that is comparable to the multi-sample ROI-based approach., Competing Interests: Compliance with Ethical StandardsLee Reeree, Jihyun Kim, Jin Chul Paeng, Jung Woo Byun, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, and Keon Wook Kang declare that they have no conflict of interest.All procedures followed were performed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2013. The study design was approved by the Institutional Review Board of the Seoul National University Hospital (H-1711-112-901). This manuscript has not been published before or is not under consideration for publication anywhere else and has been approved by all co-authors.The study design of the retrospective analysis and exemption of informed consent were approved by the Institutional Review Board of the Seoul National University Hospital.

Purpose: Herein, we report characteristics of 18 F-fluorodeoxyglucose (FDG) uptake in abdominal aortic aneurysms (AAAs) during a long-term follow-up. In addition, we investigated the association between FDG uptake and the physician decision to perform an intervention., Methods: We performed a retrospective review of 42 patients with AAAs who underwent FDG positron emission tomography (PET)/computed tomography (CT). The size of the AAA was measured in serial CT or PET/CT images. The long-term growth rate of AAAs was calculated by linear regression of the size change. Maximal SUV of the AAA (SUV AAA ) and mean SUV of the blood pool (SUV Blood ) were measured in PET/CT fusion images. To assess the FDG uptake of AAAs, the target-to-background ratio (TBR) was defined as the ratio of SUV AAA to SUV Blood . We compared FDG uptake of AAAs with the long-term growth rate of AAAs and clinical data., Results: TBR was not significantly different between patients with and without significant growth (1.55 ± 0.20 vs. 1.57 ± 0.14; P  = 0.5599). However, in patients with significant growth, TBR exhibited a significant positive correlation with the growth rate ( r 2  = 0.2601, P  = 0.0306). TBR also exhibited a significant difference between patients with and without intervention ( P  = 0.0228)., Conclusion: FDG uptake of AAA is associated with long-term growth of AAAs in a specified group that exhibits growth. FDG PET/CT may only be effective in predicting the long-term growth of AAAs in specific subgroups of patients. It is also suggested that FDG PET is potentially related to the clinical conditions of AAA patients who need surgical or interventional treatment., Competing Interests: Compliance with Ethical StandardsHyunjong Lee, Jin Chul Paeng, Kyung Hwan Kim, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, and Keon Wook Kang declare that they have no conflict of interest. This study was supported by the Korean National Research Foundation (NRF-2015R1D1A1A02062323).All procedures performed in studies involving human participants were performed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2013. This manuscript has not been published before or is not under consideration for publication anywhere else and has been approved by all co-authors.The study design of the retrospective analysis and exemption of informed consent were approved by the Institutional Review Board of the Seoul National University Hospital (H-1611-106-809).

Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.

Purpose: FDG PET is effective in treatment response evaluation of cancer. However, there is no standard method for quantitative evaluation of FDG PET, particularly regarding cytostatic drugs. We compared various FDG PET quantitative methods in terms of response determination., Methods: A total of 39 refractory metastatic colorectal cancer patients who received a multikinase inhibitor treatment were included. Baseline and posttreatment FDG PET/CT scans were performed before and two cycles after treatment. Standardized uptake value (SUV) and total lesion glycolysis (TLG) values using various margin thresholds (30-70 % of maximum SUV with increment 10 %, twice mean SUV of blood pool, SUV 3.0, and SUV 4.0) were measured, with measurement target of the hottest lesion or a maximum of five hottest lesions. Treatment response by the PERCIST criteria was also determined. Predictive values of the PET indexes were evaluated in terms of the treatment response determined by the RECIST 1.1 criteria., Results: The agreement rate was 38 % between response determined by the PERCIST and the RECIST criteria (κ = 0.381). When patients were classified into disease control group (PR, SD) and non-control group (PD) by the RECIST criteria, percent changes of TLG with various margin thresholds (particularly, 30-50 % of maximum SUV) exhibited significant differences between the two groups, and high diagnostic power for the response by the RECIST criteria. TLG-based criteria, which used a margin threshold of 50 % of maximum SUV, exhibited a high agreement with the RECIST criteria compared with the PERCIST criteria (κ = 0.606)., Conclusion: In metastatic colorectal cancer, FDG PET/CT could be effective for treatment response evaluation by using TLG measured by margin thresholds of 30-50 % of maximum SUV. Further studies are warranted regarding the optimal cutoff values for this method.

Purpose: Until now, there was no single standardized regional segmentation method of planar lung perfusion scan. We compared planar scan based two segmentation methods, which are frequently used in the Society of Nuclear Medicine, with reference to the lung perfusion single photon emission computed tomography (SPECT)/computed tomography (CT) derived values in lung cancer patients., Methods: Fifty-five lung cancer patients (male:female, 37:18; age, 67.8 ± 10.7 years) were evaluated. The patients underwent planar scan and SPECT/CT after injection of technetium-99 m macroaggregated albumin (Tc-99 m-MAA). The % uptake and predicted postoperative percentage forced expiratory volume in 1 s (ppoFEV1%) derived from both posterior oblique (PO) and anterior posterior (AP) methods were compared with SPECT/CT derived parameters. Concordance analysis, paired comparison, reproducibility analysis and spearman correlation analysis were conducted., Results: The % uptake derived from PO method showed higher concordance with SPECT/CT derived % uptake in every lobe compared to AP method. Both methods showed significantly different lobar distribution of % uptake compared to SPECT/CT. For the target region, ppoFEV1% measured from PO method showed higher concordance with SPECT/CT, but lower reproducibility compared to AP method. Preliminary data revealed that every method significantly correlated with actual postoperative FEV1%, with SPECT/CT showing the best correlation., Conclusion: The PO method derived values showed better concordance with SPECT/CT compared to the AP method. Both PO and AP methods showed significantly different lobar distribution compared to SPECT/CT. In clinical practice such difference according to different methods and lobes should be considered for more accurate postoperative lung function prediction.

Purpose: 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123 I- or 131 I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated., Methods: Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information-including histopathology, and serum markers-and several PET parameters-including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)-were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS)., Results: Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv ( p  = 0.017), TBR ( p  = 0.09), MTV ( p  = 0.02), and CV ( p  = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv ( p  = 0.021) and TBR ( p  = 0.023)., Conclusions: FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

The recent advance in hybrid imaging techniques enables offering simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) in various clinical fields. 18 F-fluorodeoxyglucose (FDG) PET has been widely used for diagnosis and evaluation of oncologic patients. The growing evidence from research and clinical experiences demonstrated that PET/MRI with FDG can provide comparable or superior diagnostic performance more than conventional radiological imaging such as computed tomography (CT), MRI or PET/CT in various cancers. Combined analysis using structural information and functional/molecular information of tumors can draw additional diagnostic information based on PET/MRI. Further studies including determination of the diagnostic efficacy, optimizing the examination protocol, and analysis of the hybrid imaging results is necessary for extending the FDG PET/MRI application in clinical oncology.

Purpose: Currently, traumatic bone diseases are diagnosed by assessing the micro (99m)Tc-hydroxymethylene diphosphonate (HDP) uptake in injured trabeculae with ongoing osteoneogenesis demonstrated by gamma correction pinhole scan (GCPS). However, the mathematic size quantification of micro-uptake is not yet available. We designed and performed this phantom-based study to set up an in-vitro model of the mathematical calculation of micro-uptake by the pixelized measurement., Methods: The micro (99m)Tc-HDP deposits used in this study were spontaneously formed both in a large standard flood and small house-made dish phantoms. The processing was as follows: first, phantoms were flooded with distilled water and (99m)Tc-HDP was therein injected to induce micro (99m)Tc-HDP deposition; second, the deposits were scanned using parallel-hole and pinhole collimator to generally survey (99m)Tc-HDP deposition pattern; and third, the scans underwent gamma correction (GC) to discern individual deposits for size measurement., Results: In original naïve scans, tracer distribution was simply nebulous in appearance and, hence, could not be measured. Impressively, however, GCPS could discern individual micro deposits so that they were calculated by pixelized measurement. Phantoms naturally formed micro (99m)Tc-HDP deposits that are analogous to (99m)Tc-HDP uptake on in-vivo bone scan. The smallest one we measured was 0.414 mm. Flooded phantoms and therein injected (99m)Tc-HDP form nebulous micro (99m)Tc-HDP deposits that are rendered discernible by GCPB and precisely calculable using pixelized measurement., Conclusions: This method can be used for precise quantitative and qualitative diagnosis of bone and joint diseases at the trabecular level.

Purpose: C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG., Methods: A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNRmax, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNRmax, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS)., Results: Median PFS of all patients was 7.9 months (range 1.0-53.8 months). In univariate analysis, MTV (cutoff 35 cm(3)) was a significant prognostic factor for PFS (P = 0.01), whereas TNRmax (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03)., Conclusion: MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNRmax is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.

Purpose: In-pentetreotide has been used for neuroendocrine tumors expressing somatostatin receptors. Recently, (68)Ga-DOTATOC PET has been used with the advantage of high image quality. In this study, we compared quantitative indices between (111)In-pentetreotide SPECT/CT and (68)Ga-DOTATOC PET/CT., Methods: Thirteen patients diagnosed with neuroendocrine tumors were prospectively recruited. Patients underwent (111)In-pentetreotide scans with SPECT/CT and (68)Ga-DOTATOC PET/CT before treatment. The number and location of lesions were analyzed on both imaging techniques to compare lesion detectability. Additionally, the maximal uptake count of each lesion and mean uptake count of the lungs were measured on both imagings, and target-to-normal lung ratios (TNR) were calculated as quantitative indices., Results: Among 13 patients, 10 exhibited lesions with increased uptake on (111)In-pentetreotide SPECT/CT and/or (68)Ga-DOTATOC PET/CT. Scans with SPECT/CT detected 19 lesions, all of which were also detected on PET/CT. Moreover, 16 additional lesions were detected on PET/CT (6 in the liver, 9 in the pancreas and 1 in the spleen). PET/CT exhibited a significantly higher sensitivity than SPECT/CT (100 % vs. 54 %, P < 0.001). TNR was significantly higher on PET/CT than on SPECT/CT (99.9 ± 84.3 vs. 71.1 ± 114.9, P < 0.001) in spite of a significant correlation (r = 0.692, P = 0.01)., Conclusion: Ga-DOTATOC PET/CT has a higher diagnostic sensitivity than (111)In-pentetreotide scans with SPECT/CT. The TNR on PET/CT is higher than that of SPECT/CT, which also suggests the higher sensitivity of PET/CT. (111)In-pentetreotide SPECT/CT should be used carefully if it is used instead of (68)Ga-DOTATOC PET/CT.

Lymphoscintigraphy is known to be a useful and non-invasive modality for the evaluation of lymphatic abnormality. However, lymphoscintigraphy has limitations in evaluating chyluria because of its lack of anatomical information. Additional single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was considered to be potentially helpful in detecting the abnormal lymphatico-renal communication. A 20-year-old male patient was referred to our hospital for evaluation of recurrent chyluria. During the third recurrence of chyluria, additional SPECT/CT along with lymphoscintigraphy was performed for evaluation. From the combined SPECT/CT images, lymphatic drainage of radiotracers to the kidney was well visualized, helping diagnosis of a patient with chyluria.

Purpose: Texture analysis on (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) scan is a relatively new imaging analysis tool to evaluate metabolic heterogeneity. We analyzed the difference in textural characteristics between non-small cell lung carcinoma (NSCLC) subtypes, namely adenocarcinoma (ADC) and squamous cell carcinoma (SqCC)., Methods: Diagnostic (18)F-FDG PET/computed tomography (CT) scans of 30y patients (median age, 67; range, 42-88) with NSCLC (17 ADC and 13 SqCC) were retrospectively analyzed. Regions of interest were manually determined on selected transverse image containing the highest SUV value in tumors. Texture parameters were extracted by histogram-based algorithms, absolute gradient-based algorithms, run-length matrix-based algorithms, co-occurrence matrix-based algorithms, and autoregressive model-based algorithms. Twenty-four out of hundreds of texture features were selected by three algorithms: Fisher coefficient, minimization of both classification error probability and average correlation, and mutual information. Automated clustering of tumors was based on the most discriminating feature calculated by linear discriminant analysis (LDA). Each tumor subtype was determined by histopathologic examination after biopsy and surgery., Results: Fifteen texture features had significant different values between ADC and SqCC. LDA with 24 automate-selected texture features accurately clustered between ADC and SqCC with 0.90 linear separability. There was no high correlation between SUVmax and texture parameters (|r| ≤ 0.62)., Conclusion: Each subtype of NSCLC tumor has different metabolic heterogeneity. The results of this study support the potential of textural parameters on FDG PET as an imaging biomarker.

Purpose: The new modality of an integrated positron emission tomography/magnetic resonance imaging (PET/MRI) has recently been introduced but not validated. Our objective was to evaluate clinical performance of (18)F-fluoro-2-deoxyglucose ((18)F-FDG) PET/MRI in patients with head and neck cancer., Methods: This retrospective study was conducted between January 2013 and February 2013. Ten patients (eight men, two women; mean age, 61.4 ± 13.4 years) with histologically proven head and neck tumors were enrolled. Whole-body PET/MRI and regional positron emission tomography (PET) with dedicated MRI were sequentially obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume, total lesion glycolysis and contrast enhancement were analyzed. A total of ten whole-body positron emission tomography (PET), ten regional positron emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium-enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two nuclear medicine physicians analyzed positron emission tomography (PET) and PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary lesions and number of metastatic lymph nodes analyzed from each image were compared., Results: Eight patients were diagnosed with head and neck cancer (one tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) attenuated by MRI showed good image quality for the lesion detection. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) detected ten primary sites and compensated for a missed lesion on dedicated MRI. A discordant number of suspicious lymph node metastases was noted according to the different images; 22, 16, 39 and 40 in the whole-body positron emission tomography (PET) only, dedicated MR, regional positron emission tomography (PET) only and regional PET/Gd-MRI, respectively. There was no distant metastasis based on analysis of whole-body positron emission tomography (PET) and whole-body PET/Dixon-volume interpolated breathhold examination (VIBE) MRI. Regional PET/Gd-MRI combined with whole-body PET/MRI modified staging in three patients. Lesions of primary tumor and suspicious metastasis were well detected on both value of SUVmax and visual analysis. The regional PET/Gd-MRI combined with whole-body PET/MRI showed convenient clinical staging performance compared with positron emission tomography (PET) and MRI alone., Conclusion: In this preliminary study, PET attenuated by MRI showed good image quality to detect lesions. And whole-body PET/MRI as a single modality was feasible for staging in a clinical setting. Whole-body positron emission tomography (PET), regional positron emission tomography (PET), dedicated MRI and regional PET/Gd-MRI showed discordant results in lesion detection. These discordant results might be synergistic effect for accurate staging.

Image quantification studies in positron emission tomography/computed tomography (PET/CT) are of immense importance in the diagnosis and follow-up of variety of cancers. In this review we have described the current image quantification methodologies employed in (18)F-fluorodeoxyglucose ((18)F-FDG) PET in major oncological conditions with particular emphasis on tumor heterogeneity studies. We have described various quantitative parameters being used in PET image analysis. The main contemporary methodology is to measure tumor metabolic activity; however, analysis of other image-related parameters is also increasing. Primarily, we have identified the existing role of tumor heterogeneity studies in major cancers using (18)F-FDG PET. We have also described some newer radiopharmaceuticals other than (18)F-FDG being studied/used in the management of these cancers. Tumor heterogeneity studies are being performed in almost all major oncological conditions using (18)F-FDG PET. The role of these studies is very promising in the management of these conditions.

Purpose: Lymph node (LN) characterization is crucial in determining the stage and treatment decisions in patient with lung cancer. Although (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has a higher diagnostic accuracy in LN characterization than anatomical imaging, differentiating between metastatic and inflammatory LNs is still challenging because both could show high (18)F-FDG uptake. The purpose of this study was to assess if the heterogeneity of the (18)F-FDG uptake could help in differentiating between inflammatory and metastatic LNs in lung cancer, and to compare with other parameters., Methods: A total of 44 patients with adenocarcinoma of the lung, who underwent preoperative (18)F-FDG PET/CT without having any previous treatments and were revealed to have (18)F-FDG-avid LNs, were enrolled. There were 52 pathology-proven metastatic lymph nodes in 26 subjects. The pathology-proven metastatic LNs were compared with 42 pathology-proven inflammatory/benign LNs in 18 subjects. The coefficient of variation (CV) was used to assess the heterogeneity of (18)F-FDG uptake by dividing the standard deviation of standardized uptake value (SUV) by mean SUV. The volume of interest was manually drawn based on the combined CT images of (18)F-FDG PET/CT (no threshold is used). Comparisons were made with the maximum standardized uptake values (SUVmax), visual assessment of (18)F-FDG uptake, longest diameter, and maximum Hounsfield units (HUmax)., Results: Metastatic lymph nodes tended to have higher CVs than the inflammatory LNs. The mean CV of metastatic LNs (0.30 ± 0.08; range: 0.08-0.55) was higher than that of inflammatory LNs (0.17 + 0.06; range, 0.07-0.32; P < 0.0001). On receiver operating characteristic (ROC) curve analysis, the area under curve was 0.901, and using 0.20 as cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 88.5 %, 76.2 %, 82.2 %, 84.3, and 83.0 % respectively. Accuracy of CV was slightly higher than SUVmax and diameter, but significantly higher than visual assessment and HUmax., Conclusions: In patients with adenocarcinoma of the lung having no prior treatments, metastatic LNs showed more heterogeneous (18)F-FDG uptake than inflammatory LNs. Measuring the CV of the SUV derived from a manual volume of interest (VOI) can be helpful in determining metastatic LN of adenocarcinoma of the lung. Including diagnostic criteria of CV into the diagnostic approach can increase the accuracy of mediastinal node status.

Purpose: Basal/acetazolamide stress (99m)Tc-HMPAO single-photon emission computed tomography (SPECT) has been widely used for evaluation of hemodynamics; however, qualitative and subjective visual assessment of cerebrovascular reserve (CVR) has been performed in clinical settings. The aim of this study was to generate parametric CVR images and evaluate its feasibility of quantification., Methods: Basal/acetazolamide stress (99m)Tc-HMPAO SPECT data from 17 patients who underwent bypass surgery or percutaneous transluminal angioplasty were used. Spatial normalization was performed and parametric CVR images were generated using relative CVR (rCVR) of each voxel proportional to CVR of the whole brain. Binary parametric maps to show area of relatively reduced CVR were generated also using threshold of rCVR < 90 %. We calculated rCVR of internal carotid artery (ICA) using the parametric CVR images and probabilistic maps for ICA territory. Pre- and postprocedural parametric CVR images were obtained and quantitative rCVRs were compared. The rCVRs were evaluated according to visual grades for regional decreased CVR., Results: Postprocedural rCVR obtained from parametric CVR images increased significantly from preprocedural rCVR. The rCVR was significantly correlated with visual grades of reduced CVR for each side of ICA territories., Conclusions: We generated parametric CVR images for basal/acetazolamide stress (99m)Tc-HMPAO SPECT. As a quantitative measurement, rCVR obtained from the parametric image was feasibly assessed hemodynamic abnormalities with preserved anatomical information.

Purpose: (11)C-Methionine PET/CT (Met-PET/CT) is a useful imaging method for detection of parathyroid adenoma; however, the reported detection rate has been variable. The current study was intended to investigate detection sensitivity and preoperative localization of parathyroid adenoma (PA) or parathyroid hyperplasia (PH) on Met-PET/CT compared with (99m)Tc-sestamibi (MIBI) scintigraphy in patients with primary hyperparathyroidism (HPT) or suspected PA., Methods: Met-PET/CT and MIBI scintigraphy images were reviewed by two nuclear medicine physicians unaware of pathologic results. Detection sensitivities and preoperative localization of detected parathyroid tissues into five predefined segments were evaluated by visual assessment and semi-quantitative analysis with ratio of standardized uptake values (SUVR) between parathyroid tissue and normal lung as reference. Linear regression analysis with SUVR and serum parathyroid hormone (sPTH) was performed for characterization of PA or PH. Predicted PTH (pPTH) was calculated and compared with sPTH in PH and PA. Each pPTH was obtained for a calculated SUVR by using linear regression model from the result of previous linear regression analysis between SUVR and sPTH., Results: In 16 patients, detection sensitivities of Met-PET/CT and MIBI scintigraphy were 91.7 % (11/12) and 41.7 % (5/12) for PA and PH including both biopsy-confirmed and clinically-suspected cases, and 100 % (8/8) and 50 % (4/8) for pathologically confirmed PA and PH cases only, respectively. Met-PET/CT showed higher performance than MIBI scintigraphy in localization of parathyroid tissues; correct localization rate was 87.5 % (7/8) on Met-PET/CT and 50 % (4/8) on MIBI scintigraphy. In semi-quantitative analysis, SUVR was linearly associated with sPTH by linear regression analysis (sPTH = 39.53 × SUVR - 89.84, p = 0.0383). There was a borderline significant difference in pPTH between PH and PA (35.1 vs 204.7 ± 164.0, p = 0.052), while there was no significant difference in sPTH between PH and PA (289 vs 230.4 ± 160.4, p = 0.305)., Conclusions: Met-PET/CT has a potential to be a useful diagnostic modality for preoperative detection and localization of parathyroid tissues with higher sensitivity than MIBI scintigraphy, and for characterization of PA or PH.

Purpose: To evaluate the reliability of quantitation of myocardial viability on cardiac F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans with three different methods of visual scoring system, autoquantitation using commercially available autoquantitation software, and infarct-size measurement using histogram-based maximum pixel threshold identification on polar-map in rat hearts., Methods: A myocardial infarct (MI) model was made by left anterior descending artery (LAD) ligation in rat hearts. Eighteen MI rats underwent cardiac FDG-PET-computed tomography (CT) twice within a 4-week interval. Myocardium was partitioned into 20 segments for the comparison, and then we quantitated non-viable myocardium on cardiac FDG PET-CT with three different methods: method A-infarct-size measurement using histogram-based maximum pixel threshold identification on polar-map; method B-summed MI score (SMS) by a four-point visual scoring system; method C-metabolic non-viable values by commercially available autoquantitation software. Changes of non-viable myocardium on serial PET-CT scans with three different methods were calculated by the change of each parameter. Correlation and reproducibility were evaluated between the different methods., Results: Infarct-size measurement, visual SMS, and non-viable values by autoquantitation software presented proportional relationship to each other. All the parameters of methods A, B, and C showed relatively good correlation between each other. Among them, infarct-size measurement (method A) and autoquantitation software (method C) showed the best correlation (r = 0.87, p < 0.001). When we evaluated the changes of non-viable myocardium on the serial FDG-PET-CT- however, autoquantitation program showed less correlation with the other methods. Visual assessment (method B) and those of infarct size (method A) showed the best correlation (r = 0.54, p = 0.02) for the assessment of interval changes., Conclusions: Commercially available quantitation software could be applied to measure the myocardial viability on small animal cardiac FDG-PET-CT scan. This kind of quantitation showed good correlation with infarct size measurement by histogram-based maximum pixel threshold identification. However, this method showed the weak correlation when applied in the measuring the changes of non-viable myocardium on the serial scans, which means that the caution will be needed to evaluate the changes on the serial monitoring.

Purpose: The aim of this study was to evaluate the feasibility of FP-CIT PET template-based quantitative analysis on F-18 FP-CIT PET in patients with de novo Parkinson's disease (PD), compared with MR-based and manual methods. We also assessed the correlation of quantitative parameters of those methods with clinical severity of the disease., Methods: Forty patients with de novo PD underwent both MRI and F-18 FP-CIT PET. Images were spatially normalized to a standardized PET template. Mean counts of 4 ROIs: putamen, caudate, occipital cortex and cerebellum, were obtained using the quantification program, Korean Statistical Probabilistic Anatomical Map (KSPAM). Putamen-to-caudate ratio (PCR), asymmetry index (ASI), specific-to-nonspecific ratios with two different references: to occipital cortex (SOR) and cerebellum (SCR) were compared. Parameters were also calculated from manually drawn ROI method and MR-coregistrated method., Results: All quantitative parameters showed significant correlations across the three different methods, especially between the PET-based and manual methods. Among them, PET-based SOR and SCR values showed an excellent correlation and concordance with those of manual method. In relationship with clinical severity, only ASI achieved significantly inverse correlations with H&Y stage and UPDRS motor score. There was no significant difference between the quantitative parameters of both occipital cortex and cerebellum in all three methods, which implied that quantitation using PET-based method could be reproducible regardless of the reference region., Conclusions: Quantitative parameters using FP-CIT PET template-based method correlated well with those using laborious manual method with excellent concordance. Moreover, PET-based quantitation was less influenced by the reference region than MR-based method. It suggests that PET-based method can provide objective and quantitative parameters quickly and easily as a feasible analysis in place of conventional method.

Purpose: This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter., Methods: The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP-producing cells and in AFP-nonproducing cells was investigated using (125)I uptake assay and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of (131)I on AdAFPhNIS-infected HCC cells was studied using an in vitro clonogenic assay. In addition, tumor-bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained., Results: The expression of hNIS was efficiently demonstrated by (125)I uptake assay in AFP-producing cells, but not in AFP-nonproducing cells. AFP-producing HCC-targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP-producing cells caused more sensitivity to (131)I than that in AFP-nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging., Conclusions: An AFP-producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP-producing HCC-specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system.

Purpose: Usefulness of FDG PET-CT in monitoring response in locally advanced gastric cancer has been reported. The purpose of this study was to evaluate the related factors to detect measurable diseases in advanced gastric cancer on FDG PET-CT., Methods: We retrospectively reviewed 38 patients diagnosed as having advanced gastric cancer. We defined the measurable diseases when there was visualized tumor of which maximum standardized uptake value (SUVmax) was higher than 1.35*SUVmax of liver + 2*SD of liver SUV. We evaluated what kinds of factors from the clinicopathologic features were related to identifying measurable diseases., Results: Of 38 patients with advanced gastric cancer, 18 (50 %) had measurable tumors on FDG PET-CT. Measurable tumors were significantly more frequent in well or moderately differentiated adenocarcinoma (70.5 % vs 35.3 %, p < 0.05), in the tumors located at antrum or angle (66.7 % vs 29.4 %, p < 0.05) and in the elderly group (age of 55 years old or more, 72.0 % vs 8.3 %, p < 0.001) than the others, respectively. By multivariate analysis, age at diagnosis was the only independent predictor for the measurable disease on FDG PET-CT., Conclusion: We found that age at diagnosis, as well as histologic types and location of tumors, were the affecting factors to detect measurable disease on FDG PET-CT in patients with advanced gastric cancer. Our study suggests that elderly patients of age of 55 years old or more can frequently have T-measurable disease on FDG PET-CT in advanced gastric cancer and FDG PET-CT will be helpful to monitor measurable disease.

Purpose: The aim of this study was to assess the diagnostic efficacy of PET/CT using various parameters for the characterization of adrenal nodules in lung cancer patients., Methods: Sixty-one adrenal nodules in 51 lung cancer patients were evaluated. The final diagnosis was based on histology (n = 2) or imaging follow-up (n = 59, range of follow-up: 7-57 months, median 27 months). Each adrenal nodule was analyzed using four parameters of PET/CT: the maximum standardized uptake value (SUVmax), the adrenal nodule/liver ratio of the SUV (SUV ratio), Hounsfield units (HU) and size. The optimal cutoff of each parameter for the identification of metastatic nodule was determined by ROC analysis and then the diagnostic efficacy was compared among the parameters., Results: Of the 61 adrenal nodules, 45 (73%) were considered metastasis. The optimal cutoff values of the parameters were SUVmax >2.7, SUV ratio >1.3, HU >18 and size >20 mm, respectively. The sensitivity, specificity and accuracy by SUVmax >2.7 were 88.9%, 87.5% and 88.5%, and those by SUV ratio >1.3 were 84.4%, 100% and 88.5%, respectively. The combination of SUV ratio >1.3 and HU >18 had sensitivity of 97.7%, specificity of 81.2% and accuracy of 93.4% to predict adrenal metastasis in patients with lung cancer., Conclusion: SUV ratio from F-18 FDG PET/CT could identify the adrenal metastasis in lung cancer patients. The combination of SUV ratio and HU can improve the accuracy of differentiating benign and metastatic adrenal lesions in lung cancer patients.

Objective: We determined the cytotoxic properties of cytochrome P450 4B1 (CYP4B1) activated 4-ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) in rat glioma to verify the CYP4B1/4-ipo or 2-AA system for prodrug-activating gene therapy., Methods: The cyp4B1 cDNA was cloned into pcDNA3.1/Hygro from rabbit lung total RNA (pcDNA-cyp4B1). Lentiviral vector encoding firefly luciferase (fLuc) was infected into C6 (rat glioma), and the fLuc-expressing cell was selected (C6-L). After transfection with pcDNA-cyp4B1 vector into C6-L, the single clone expressing cyp4B1 gene was selected (C6-CL). Prodrug for various concentrations of 4-ipo or 2-AA was treated for 72 h and 96 h. The cell survival rate of C6-CL was determined using MTT assay and trypan-blue dye exclusion methods., Results: By RT-PCR analysis, fLuc and CYP4B1 expression was detected in C6-CL, but not in C6. MTT assay and trypan-blue dye exclusion showed that IC50 of C6-CL was 0.3 mM and <0.01 mM after 4-ipo or 2-AA treatment at 96 h or 72 h exposure, respectively. Cell survivals of C6-CL were more rapidly reduced after treatment with 4-ipo or 2-AA than those of C6-L cells. The cell survival rate with MTT and trypan-blue dye exclusion assay was well correlated with fLuc activity in C6-CL cells., Conclusion: CYP4B1-based prodrug-activating gene therapy may have the potential to treat glioma and the cytotoxic effects of CYP4B1 enzyme activated 4-ipo or 2-AA in C6, and could be clearly determined by bioluminescent activity in C6-CL.

Purpose: The object of this study was to evaluate the prevalence and characteristics of brown adipose tissue (BAT) in Korean subjects using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)., Methods: Six thousand and five consecutive (18)F-FDG PET/CT scans of 5,115 patients (3,007 females and 2,108 males, mean age 53.5 years) were retrospectively reviewed. We characterized the nature of BAT, such as its location, and we assessed the influence of sex, age, body mass index (BMI), and temperature on BAT., Results: The prevalence of BAT in Koreans in a single (18)F-FDG PET/CT scan in average conditions was 1.07%. The BAT detection rate was higher in females than males (1.32% vs 0.73%), and also with younger age (7.94% vs 0.73%), lower BMI (BMI with BAT, 21.1 vs BMI without BAT, 23.15) and cold outdoor temperature (1.65% vs 0.49%). The most frequent location of BAT was the supraclavicular area (left, 0.91%; right, 0.88%) and ventral neck area (left, 0.62%; right, 0.63%)., Conclusions: The characteristics of BAT in Koreans are not different from those described for Caucasians. However, the low prevalence of BAT in our study might be related to some scan condition like ambient temperature, but further study is needed.

Purpose: The purpose of this study was to compare the uptakes and diagnostic accuracies between 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) and O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) PET in patients with a clinical suspicion of having a recurrence of glioma after multimodality treatment., Methods: Thirty-two patients who underwent FLT and FET PET due to abnormal enhancement on magnetic resonance (MR) images were included. According to surgical confirmation or follow-up results, patients were divided into those with therapy-related benign changes (TRBCs) and those with recurrence. Recurrences were divided again into initial low-grade glioma (LGG) and high-grade glioma (HGG). The uptakes of FLT and FET were compared with the maximum standardized uptake value (SUVmax) and lesion-to-normal ratio (LNR). The diagnostic accuracies were compared via a receiver-operating-characteristic (ROC) curve analysis., Results: The LNRs of FLT in recurrences with initial HGG (8.26 ± 5.02) were significantly higher than those in recurrences with initial LGG (3.43 ± 2.14) and TRBC (1.81 ± 0.60). The LNRs of FET in recurrence with initial HGG (2.70 ± 0.48) and LGG (3.03 ± 1.32) were significantly higher than those in the TRBC (1.60 ± 0.47). The areas under the ROC curve (AUCs) of FLT and FET for initial LGG were 0.768 and 0.893, respectively. The AUCs of FLT and FET for initial HGG were 1.000 and 0.964. However, there were no statistical significances. The results for comparing with SUVmax were the same as those with LNR., Conclusions: Uptakes of FLT were different according to initial grade in patients with recurrent glioma, but those of FET were not. However, there were no statistical significances in the diagnostic accuracies according to initial grade between the two tracers in this study.