Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.

Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging.

Clinical feasibility of deep learning-based synthetic CT images from T2-weighted MR images for cervical cancer patients compared to MRCAT.

This work aims to investigate the clinical feasibility of deep learning-based synthetic CT images for cervix cancer, comparing them to MR for calculating attenuation (MRCAT). Patient cohort with 50 pairs of T2-weighted MR and CT images from cervical cancer patients was split into 40 for training and 10 for testing phases. We conducted deformable image registration and Nyul intensity normalization for MR images to maximize the similarity between MR and CT images as a preprocessing step. The processed images were plugged into a deep learning model, generative adversarial network. To prove clinical feasibility, we assessed the accuracy of synthetic CT images in image similarity using structural similarity (SSIM) and mean-absolute-error (MAE) and dosimetry similarity using gamma passing rate (GPR). Dose calculation was performed on the true and synthetic CT images with a commercial Monte Carlo algorithm. Synthetic CT images generated by deep learning outperformed MRCAT images in image similarity by 1.5% in SSIM, and 18.5 HU in MAE. In dosimetry, the DL-based synthetic CT images achieved 98.71% and 96.39% in the GPR at 1% and 1 mm criterion with 10% and 60% cut-off values of the prescription dose, which were 0.9% and 5.1% greater GPRs over MRCAT images.

Effect of ¹8F-FDG administration on measurements of bone mineral density and body composition by dual-energy X-ray absorptiometry.

The purpose of this study was to determine whether antecedent administration of ¹8F-fluorodeoxyglucose (FDG) used in positron emission tomography (PET) scanning results in corruption of bone mineral density (BMD) and body composition measured by dual-energy X-ray absorptiometry (DXA) system. DXA measurements of BMD and body composition had been performed twice, before and after ¹8F-FDG PET scan in 30 patients. The comparison of pre-values and post-values of all BMD values showed a decrease after the injection. However, only the decrease of whole-body BMD (WB-BMD) was statistically significant (p < 0.05). Whole-body fat mass had increased and whole-body lean body mass had decreased after the injection of ¹8F-FDG, and these were statistically significant (p < 0.05). There is statistically significant correlation between the injected ¹8F-FDG dose and a decrease of WB-BMD (r = -0.405; p < 0.05). The findings of this study suggest that when both ¹8F-FDG PET and DXA measurements for whole-body composition are performed in close-time proximity, ¹8F-FDG PET scans should follow the DXA measurement. Otherwise, BMD measurements of total femur or lumbar spine could be followed by ¹8F-FDG PET in close-time proximity.

The therapeutic effects on U87 and SAS cells using Proton Linac based Boron Neutron Capture Therapy in Korea.

A proton linac based boron neutron capture therapy system (A-BNCT, 10MeV, 4mA) was successfully developed in Korea. We performed in vitro experiments with U87 and SAS cells and revealed the efficacy of a binary therapy BNCT using epithermal neutrons and boronophenylalanine (BPA). The results revealed that BNCT showed cancer cell selectivity and caused cell death. Further in vitro studies can be a valuable method to characterize an A-BNCT system. We expect BNCT to become a treatment option for cancer patients.

Versatile and Finely Tuned Albumin Nanoplatform based on Click Chemistry.

Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and the affecting factors were not well evaluated, which could hamper the clinical translation of albumin-based nanoplatforms. Herein, we developed a finely tuned click-chemistry based albumin nanoplatform (CAN) with a longer circulation half-life and an efficient tumor targeting ability. Methods: CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) by reacting albumin with various molar ratios of ADIBO. The number of attached ADIBO moieties was determined using matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Second, the desired modalities including azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using strain-promoted alkyne-azide cycloaddition reaction (SPAAC reaction). The biodistribution and targeting efficiency of functionalized CANs were demonstrated in mice. Results: The degree of functionalization (DOF) and resulting in vivo biodistribution was controlled precisely using the click chemistry approach. Specifically, the numbers of attached azadibenzocyclooctyne (ADIBO) moieties on albumin, the DOF, were optimized by reacting albumin with varying molar ratios of ADIBO with a high reproducibility. Furthermore, we developed a simple and efficient method to estimate the DOF using UV-visible spectrophotometry (UV-vis), which was further validated by matrix-assisted laser desorption ionization time of flight (MALDI-TOF). The biodistribution of CAN could be controlled by DOF, and CAN with an optimized DOF showed a long circulation half-life (> 18 h). CAN was further functionalized using a simple click chemistry reaction with an azide functionalized chelator, a fluorescence dye, and folate. 64Cu- and folate-labeled CAN (64Cu-CAN-FA) showed effective and specific folate receptor targeting in vivo, with an over two-fold higher uptake than the liver at 24 h post-injection. Conclusions: Our development from the precisely controlled DOF demonstrates that an optimized CAN can be used as a multifunctional nanoplatform to obtain a longer half-life with radioisotopes and ligands, and provides an effective method for the development of albumin-based tumor theranostic agents.

Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication.

A change in tumor size is a well-validated and commonly used value for evaluating response to chemotherapy in cancer. Metabolic changes induced by chemotherapy are related to prognosis in several tumor types. However, the clinical implication of metabolic changes in patients with advanced gastric cancer (AGC) undergoing chemotherapy remains unclear. We aimed to evaluate response of tumor size and metabolism in AGC during chemotherapy and to reveal the relationship between them in view of their impact on patient survival. Methods: We prospectively enrolled patients with AGC before the initiation of first-line palliative chemotherapy. Using baseline and follow-up contrast-enhanced CT and 18F-FDG PET, we assessed the tumor diameter, SUVmax, and total lesion glycolysis in each lesion and their changes during chemotherapy at the same time. We included all lesions with the maximal longest diameters over 1 cm on CT, and each lesion was evaluated by matched 18F-FDG PET. We analyzed the association between changes in tumor metabolism and tumor size and performed outcome analysis on overall survival (OS) and progression-free survival (PFS). Results: Seventy-four patients were enrolled, and the number of all lesions included in this study was 620. Compared with adenocarcinomas, poorly cohesive carcinomas demonstrated lower SUVmax irrespective of tumor size (P < 0.001). Human epidermal growth factor receptor 2 (HER2)-positive tumors showed higher SUVmax than HER2-negative tumors (P = 0.002). The changes in SUVmax due to chemotherapy had a linear correlation with the changes in tumor size of each lesion, and a 30% tumor size reduction was associated with a 50% SUVmax reduction (P < 0.001). Total lesion glycolysis changes also correlated with tumor size changes (P < 0.001). Better OS and PFS were obtained in patients with both tumor size and SUVmax reduction than in patients with either size or SUVmax reduction only (OS, P = 0.003; PFS, P = 0.038). Conclusion: Changes in tumor metabolism induced by chemotherapy correlated with changes in tumor size in AGC. Considering both changes in metabolism and size could help predict a more accurate prognosis for AGC patients undergoing chemotherapy.

Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting.

OBJECTIVE: The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model. METHODS: Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE. RESULTS: The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered. CONCLUSION: Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.

Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.

OBJECTIVE: Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model. METHODS: The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g. RESULTS: A high yield of Tc-99m ECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG-RRL accumulated minimally in inflammatory lesions. CONCLUSIONS: We successfully developed Tc-99m ECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.

Synthesis and Evaluation of (99m)Tc-Labeled Folate-Tripeptide Conjugate as a Folate Receptor-Targeted Imaging Agent in a Tumor-Bearing Mouse Model.

PURPOSE: The folate receptor (FR) is an attractive molecular target since it is overexpressed in a variety of human tumors. The purpose of the present study was to synthesize and evaluate the feasibility of a novel (99m)Tc-ECG-EDA (Glu-Cys-Gly-ethylenediamine)-folate as an FR-positive tumor imaging agent in a mouse tumor model. MATERIALS AND METHODS: ECG-EDA-folate was synthesized using solid phase peptide synthesis (SPPS) and radiolabeled with (99m)Tc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of (99m)Tc-ECG-EDA-folate, serial scintigraphy and micro-SPECT/CT imaging were performed at various time points with and without pre-administration of excess free folate. Mean count densities (MCD) for regions of interest drawn on KB tumors and major normal organs at each time point were measured, and uptake ratios of tumor to normal organs were calculated. RESULTS: ECG-EDA-folate was labeled with (99m)Tc with high radiolabeling efficiency and stability (>96 %). FR-positive tumors were clearly visualized on both scintigraphy and micro-SPECT/CT images and the tumor uptake of (99m)Tc-ECG-EDA-folate was markedly suppressed with faint visualization of tumors by pre-administration of excess free folate on serial planar scintigraphy, indicating FR-specific binding of the agent. Furthermore, semiquantitative analysis of MCD data showed again that both tumor MCD and tumor-to-normal organ ratios decreased considerably by pre-administration of excess free folate, supporting FR-specific tumor uptake. Tumor-to-normal organ ratios approximately increased with time after injection until 4 h. CONCLUSION: The present study demonstrated that (99m)Tc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR-positive tumors in a mouse tumor model.

Os vesalianum pedis detected with bone SPECT/CT.

We present an 18-year-old man with pain at the lateral aspect of his left foot. Radiograph showed abnormal ossicle in the proximal aspect of the left fifth metatarsal tuberosity, which was articulated with the fifth metatarsal and cuboid bones. Bone scintigraphy and SPECT/CT demonstrated increased uptakes at the ossicles in the proximal aspect of both fifth metatarsal bones. CT revealed that the ossicle and the adjacent bones have well-corticated margins. The diagnosis was os vesalianum, a rare accessory bone of the foot. We have reported the SPECT/CT bone scan findings of the os vesalianum.

Synovial hemangioma of Hoffa fat pad demonstrated by RBC SPECT/CT.

Synovial hemangioma of Hoffa fat pad is an extremely rare disease, which occurs in the knee joints. Because synovial hemangioma often shows nonspecific symptoms, such as pain, swelling, limping, or limitation of motion, diagnosis could be delayed in many cases. We present a 7-year-old boy referred to our department for Tc red blood cell (RBC) scan for the confirmation of hemangioma suggested by the MRI. RBC scan demonstrated intense radioactivity accumulation in Hoffa pad of right knee joint, and subsequent excision biopsy revealed the mass as venous hemangioma.

Synthesis and evaluation of Tc-99m DTPA-glutathione as a non-invasive tumor imaging agent in a mouse colon cancer model.

PURPOSE: Glutathione (GSH) plays a critical role in detoxification reactions by reducing the levels of reactive oxygen species in cancer cells. This study aimed to develop technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA)-GSH as a tumor imaging agent, and to evaluate the diagnostic performance of Tc-99m DTPA-GSH in terms of its ability to differentiate tumors from inflammatory lesions. METHODS: DTPA-GSH was synthesized by reaction of GSH with DTPA anhydride under anhydrous conditions in a nitrogen atmosphere. DTPA-GSH was then reacted with Tc-99m sodium pertechnetate in a tin (II) chloride (SnCl2) solution. Gamma camera imaging was performed after intravenous injection of Tc-99m DTPA-GSH into a mouse CT-26 colon cancer model, or a mouse model of inflammation induced by the intramuscular injection of Freund's complete adjuvant. RESULTS: DTPA-GSH was successfully prepared via a straightforward synthetic procedure and radiolabeled with Tc-99m at a high labeling efficiency (>95%). Tc-99m DTPA-GSH was strongly internalized by tumors in colon cancer model mice, with the tumor-to-normal muscle ratio of the complex reaching 4.3±0.9 at 4 h. By contrast, Tc-99m DTPA-GSH showed relatively weak uptake in inflammatory lesions (target-to-non-target ratio=2.0±0.3 at 4 h). A competition study showed that the uptake of Tc-99m DTPA-GSH into tumors was blocked by co-injection with high concentrations of free GSH. CONCLUSIONS: The results of this work indicate that Tc-99m DTPA-GSH is a good candidate for development as a non-invasive tumor imaging agent. Furthermore, Tc-99m DTPA-GSH effectively distinguished between cancerous tissue and inflammatory lesions.

Abdominal aortic aneurysm with bony erosion mimicking recurrent non-Hodgkin lymphoma on FDG PET/CT.

An 80-year-old man with a history of non-Hodgkin lymphoma in complete remission after chemotherapy in 2009 presented with lumbar pain. MRI demonstrated anterior L4 bony erosions. FDG PET/CT revealed the large retroperitoneal mass with central photopenia and a mildly hypermetabolic rim. Ultrasound revealed a dilated aorta with atherosclerotic plaque and eccentric mural thrombus. A newly developed mass-like lesion in a patient with history of lymphoma could be mistaken for lymphoma recurrence on FDG PET/CT.

Novel Tc-99m labeled ELR-containing 6-mer peptides for tumor imaging in epidermoid carcinoma xenografts model: a pilot study.

OBJECTIVE: ELR-containing peptides targeting CXCR2 could be the excellent candidate for targeting ligand of molecular tumor imaging. In this study, we had developed two ELR-containing 6-mer peptides and evaluated the diagnostic performance of Tc-99m labeled 6-mer peptides as a molecular imaging agent in murine models bearing KB epidermoid carcinoma. METHODS: Peptides were synthesized using Fmoc solid phase peptide synthesis. Radiolabeling efficiency with Tc-99m was evaluated using instant thin-layer chromatography. In KB epidermoid cancer-bearing mice, gamma images had acquired and tumor-to-muscle uptake ratio was calculated. Competition and biodistribution studies had performed. RESULTS: Two 6-mer peptides, ELR-ECG and ECG-ELR were successfully synthesized. After radiolabeling procedures with Tc-99m, the complex Tc-99m ELR-ECG and Tc-99m ECG-ELR were prepared in high yield. In the gamma camera imaging of murine model, Tc-99m ELR-ECG was substantially accumulated in the subcutaneously engrafted tumor and tumor uptake had been suppressed by the free ELR co-injection. However, Tc-99m ECG-ELR was minimally accumulated in the tumor. CONCLUSIONS: Two ELR-containing 6-mer peptides, ELR-ECG and ECG-ELR, were developed as a molecular imaging agent to target CXCR2 of epidermoid carcinoma. Tc-99m ELR-ECG had showed significant uptake in tumor and it was good candidate for a tumor imaging.

Direct Determination of Lean Body Mass by CT in F-18 FDG PET/CT Studies: Comparison with Estimates Using Predictive Equations.

PURPOSE: The purpose of this study was to estimate lean body mass (LBM) using CT (LBM CTs) and compare the results with LBM estimates of four different predictive equations (LBM PEs) to assess whether LBM CTs and LBM PEs can be used interchangeably for SUV normalization. METHODS: Whole-body F-18 FDG PET/CT studies were conducted on 392 patients. LBM CT1 is modified adipose tissue-free body mass, and LBM CT2 is adipose tissue-free body mass. Four different PEs were used for comparison (LBM PE1-4). Agreement between the two measurement methods was assessed by Bland-Altman analysis. We calculated the difference between two methods (bias), the percentage of difference, and the limits of agreement, expressed as a percentage. RESULTS: For LBM CTs vs. LBM PEs, except LBM PE3, the ranges of biases and limits of agreement were -3.77 to 3.81 kg and 26.60-35.05 %, respectively, indicating the wide limits of agreement and differing magnitudes of bias. For LBM CTs vs. LBM PE3, LBM PE3 had wider limits of agreement and greater positive bias (44.28-46.19 % and 10.49 to 14.04 kg, respectively), showing unacceptably large discrepancies between LBM CTs and LBM PE3. CONCLUSION: This study demonstrated that there are substantial discrepancies between individual LBM CTs and LBM PEs, and this should be taken into account when LBM CTs and LBM PEs are used interchangeably between patients.

Comparison of SUVs Normalized by Lean Body Mass Determined by CT with Those Normalized by Lean Body Mass Estimated by Predictive Equations in Normal Tissues.

PURPOSE: Standardized uptake values (SUVs) normalized by lean body mass (LBM) determined by CT were compared with those normalized by LBM estimated using predictive equations (PEs) in normal liver, spleen, and aorta using (18)F-FDG PET/CT. METHODS: Fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) was conducted on 453 patients. LBM determined by CT was defined in 3 ways (LBMCT1-3). Five PEs were used for comparison (LBMPE1-5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SULCT1-3, SULPE1-5). Agreement between methods was assessed by Bland-Altman analysis. Percentage difference and percentage error were also calculated. RESULTS: For all liver SULCTs vs. liver SULPEs except liver SULPE3, the range of biases, SDs of percentage difference and percentage errors were -0.17-0.24 SUL, 6.15-10.17 %, and 25.07- 38.91 %, respectively. For liver SULCTs vs. liver SULPE3, the corresponding figures were 0.47-0.69 SUL, 10.90-11.25 %, and 50.85-51.55 %, respectively, showing the largest percentage errors and positive biases. Irrespective of magnitudes of the biases, large percentage errors of 25.07-51.55 % were observed between liver SULCT1-3 and liver SULPE1-5. The results of spleen and aorta SULCTs and SULPEs comparison were almost identical to those for liver. CONCLUSION: The present study demonstrated substantial errors in individual SULPEs compared with SULCTs as a reference value. Normalization of SUV by LBM determined by CT rather than PEs may be a useful approach to reduce errors in individual SULPEs.

Dual-time-point FDG PET/CT: Is It Useful for Lymph Node Staging in Patients with Non-Small-Cell Lung Cancer?

PURPOSE: Dual-time-point (DTP) FDG PET/CT has been shown to be useful for lymph node (LN) staging in patients with non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the LN staging ability of DTP FDG PET/CT in the predominant area of pulmonary tuberculosis. METHODS: Sixty-nine NSCLC patients underwent DTP PET/CT. Regions of interest were placed on each LN of each station, and the maximum SUVs were measured. Three variables were obtained: (1) the SUV on the early scan (SUVearly), (2) the SUV on the delayed scan (SUVdelayed), and (3) the retention index of the SUV (RI). Each patient had one final LN stage and three other LN stages according to the cutoff values of SUVearly, SUVdelayed, and RI. RESULTS: In the LN-based analysis, the area under the ROC curve of SUVdelayed (0.884) was significantly larger (P < 0.01) than those of SUVearly (0.868) and RI (0.717). Among the three variables, SUVdelayed was more accurate (P < 0.01) for detecting the mediastinal LN metastasis than SUVearly and RI. In the patient-based analysis, SUVdelayed had correctly determined LN stages in 55 of 69 patients (sensitivity, specificity, and accuracy = 88.7 %, 50.0 %, and 79.7 %), whereas SUVearly and RI correctly determined LN stages in 53 and 52 patients, respectively. CONCLUSIONS: In this study, comparing the diagnostic efficacy of SUVearly, SUVdelayed, and RI for LN staging in patients with NSCLC, SUVdelayed was the most accurate variable for LN staging. DTP PET/CT could provide improved diagnostic accuracy for the LN staging of NSCLC.

Optimal CT Number Range for Adipose Tissue When Determining Lean Body Mass in Whole-Body F-18 FDG PET/CT Studies.

PURPOSE: The aim of this study was to define an optimal CT number range applicable to adipose tissue (AT) measurement in modern PET/CT systems. METHODS: CT number (in Hounsfield units, HU) was measured in three different pure AT compartments in 53 patients. CT number range for AT was determined in three different ways, including pixel histogram analysis, to take the effect of partial volume averaging into account. The effect of changing the CT number range for AT on the total AT volume was investigated. RESULTS: The lower limits for CT number for pure subcutaneous AT, retroperitoneal AT, and visceral AT were -140, -140, and -130 HU, respectively. The corresponding upper limits were -70, -71, and -52 HU. The CT number range for AT using three methods when considering partial volume averaging was -144 to -141 HU to -30 to -33 HU, showing similar values between the three methods. The optimal CT number range for AT based on these data was -140 to -30 HU. Increases in total AT volume of 7.5 % and 1.8 % were found when the upper or lower limit was extended using 10 HU intervals, respectively, compared with the reference range of -140 to -30 HU. CONCLUSION: This study demonstrated that the optimal CT number range of AT that is applicable to modern PET/CT systems can be defined as -140 to -30 HU. The use of this CT number range of AT allowed lean body mass to be determined in whole-body F-18 FDG PET/CT studies.

Assessment of cerebral hemodynamics to acetazolamide using brain perfusion SPECT in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy caused by mutations in the Notch3 gene located on chromosome 19, leading to 4 cardinal features with aura, cerebrovascular ischemic events, mood disturbances, and dementia. Acetazolamide (ACZ) has been promoted as a drug to determine cerebral hemodynamics, including cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in patients with cerebrovascular disease. In CADASIL patients with small-vessel disease, ACZ may be possible to increase CBF. We present that reduced CBF was dramatically improved after administration of ACZ on Tc-99m ECD brain perfusion SPECT in a CADASIL patient.