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Y90 Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort.
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Y90 Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort.

J Nucl Med. 2017 Dec 07;:

Authors: Abouchaleh N, Gabr A, Ali R, Al Asadi A, Mora RA, Kallini JR, Marshall K, Kulik L, Mouli S, Ladner DP, Abecassis M, Caicedo JC, Riaz A, Lewandoski RJ, Salem R

Abstract
Purpose: To report survival outcomes for advanced stage hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) treated with radioembolization (Y90). Methods: With IRB approval we searched our prospectively acquired database for patients treated with Y90 between 2003 and 2017. Inclusion criteria were patients who had advanced stage HCC with tumor PVT. In order to minimize confounding effect, patients with metastases were excluded. Clinical and laboratory data were collected at baseline and 1 month post-Y90. Long-term survival outcomes were reported stratified by Child-Pugh (CP). Overall survival (OS) was calculated using Kaplan Meier. Multivariate analysis was conducted using Cox-proportion harzards. A subanalysis for patients with high alpha-fetoprotein (AFP) (>100 ng/dl) was conducted. Results: Between 2003 and 2017, 185 patients with PVT related to HCC had Y90. Seventy-four patients (40%) were CP-A, 51 (28%) were CP-B7 and 60 (32%) were ≥CP-B8. Median OS for CP-A patients was 13.3 months (95%CI: 8.7-15.7). CP-B7 patients had a median OS of 6.9 months (95%CI: 5.3-10.1). CP-≥B8 patients had a median OS of 3.9 months (95%CI: 2.9-5.0). On multivariate analysis, baseline bilirubin, ascites, and AFP were more significant prognosticators. Out of 123 patients with high AFP (>100 ng/dl), 12 patients restored normal AFP levels (<13 ng/dl) and exhibited median OS of 23.9 months (CI: 20.1-124.1). Conclusion: Y90 radioembolization can serve as a safe and effective treatment for advanced stage HCC patients with tumor PVT. OS outcomes are affected by baseline liver function, tumor size and AFP level.

PMID: 29217739 [PubMed - as supplied by publisher]




Radiolabeled (4-Fluoro-3-iodobenzyl)guanidine improves imaging and targeted radionuclide therapy of norepinephrine transporter-expressing tumors.
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Radiolabeled (4-Fluoro-3-iodobenzyl)guanidine improves imaging and targeted radionuclide therapy of norepinephrine transporter-expressing tumors.

J Nucl Med. 2017 Dec 07;:

Authors: Yamaguchi A, Hanaoka H, Higuchi T, Tsushima Y

Abstract
Fluorine-18 (18F)/Iodine-131 (131I)-labeled (4-Fluoro-3-iodobenzyl)guanidine (FIBG) have been a promising yet unattainable derivative of radioiodine-labeled meta-iodobenzylguanidine (MIBG), because of the complex radiofluorination method. Here, we proposed a 2-step radiosynthetic method for 18F-FIBG, and evaluated the diagnostic and therapeutic potential of 18F-FIBG and 131I-FIBG in a pheochromocytoma model (PC-12). Methods:18F-FIBG was prepared from a (mesityl)(aryl)iodonium salt precursor in the presence of a copper-catalyst. Biodistribution studies, PET imaging, and therapeutic study were performed on the PC-12 xenograft mice with either 18F- or 131I-FIBG. The association between the therapeutic effect and the tumor uptake of pre-therapy 18F-FIBG-PET was also evaluated. Results: The copper-mediated radiofluorination method readily yielded 18F-FIBG, as well as its regioisomer, 18F-IFBG. The isolated 18F-FIBG showed higher accumulation in the PC-12 xenograft tumor than in any other organ. The high tumor uptake of 18F-FIBG allowed clear tumor visualization in the PET image as early as 1 h after injection, with an excellent tumor-to-background ratio. A biodistribution study with 131I-FIBG revealed its higher and prolonged retention in the tumor in comparison with MIBG. As a result, a therapeutic dose of 131I-FIBG delayed tumor growth significantly more than 131I-MIBG. The tumor uptake of 18F-FIBG was proportional to the therapeutic effect of 131I-FIBG. Conclusion: These results suggest the potential usefulness of FIBG as a diagnostic and therapeutic agent for the management of NET-expressing tumors.

PMID: 29217738 [PubMed - as supplied by publisher]




Is Exercise Treadmill Time or Reduction in Myocardial Ischemia the Appropriate Primary Endpoint to Assess Success of Percutaneous Coronary Intervention in Stable Angina (ORBITA)?
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Is Exercise Treadmill Time or Reduction in Myocardial Ischemia the Appropriate Primary Endpoint to Assess Success of Percutaneous Coronary Intervention in Stable Angina (ORBITA)?

J Nucl Med. 2017 Dec 07;:

Authors: Dilsizian V, Erario M

PMID: 29217737 [PubMed - as supplied by publisher]




Generation of structural MR images from amyloid PET: Application to MR-less quantification.
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Generation of structural MR images from amyloid PET: Application to MR-less quantification.

J Nucl Med. 2017 Dec 07;:

Authors: Choi H, Lee DS

Abstract
Structural magnetic resonance (MR) images concomitantly acquired with PET images can provide crucial anatomical information for precise quantitative analysis. However, in the clinical setting, not all the subjects have corresponding MR. Here, we developed a model to generate structural MR images from amyloid PET using deep generative networks. We applied our model to quantification of cortical amyloid load without structural MR. Methods: We used florbetapir PET and structural MR data of Alzheimer's Disease Neuroimaging Initiative database. The generative network was trained to generate realistic structural MR images from florbetapir PET images. After the training, the model was applied to the quantification of cortical amyloid load. PET images were spatially normalized to the template space using the generated MR and then standardized uptake value ratio (SUVR) of the target regions was measured by predefined regions-of-interests. A real MR-based quantification was used as the gold standard to measure the accuracy of our approach. Other MR-less methods, a normal PET template-based, multi-atlas PET template-based and PET segmentation-based normalization/quantification methods, were also tested. We compared performance of quantification methods using generated MR with that of MR-based and MR-less quantification methods. Results: Generated MR images from florbetapir PET showed visually similar signal patterns to the real MR. The structural similarity index between real and generated MR was 0.91 ± 0.04. Mean absolute error of SUVR of cortical composite regions estimated by the generated MR-based method was 0.04±0.03, which was significantly smaller than other MR-less methods (0.29±0.12 for the normal PET-template, 0.12±0.07 for multiatlas PET-template and 0.08±0.06 for PET segmentation-based methods). Bland-Altman plots revealed that the generated MR-based SUVR quantification was the closest to the SUVR values estimated by the real MR-based method. Conclusion: Structural MR images were successfully generated from amyloid PET images using deep generative networks. Generated MR images could be used as template for accurate and precise amyloid quantification. This generative method might be used to generate multimodal images of various organs for further quantitative analyses.

PMID: 29217736 [PubMed - as supplied by publisher]




ImmunoPET in pontine glioma : more than meets the eye ?
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ImmunoPET in pontine glioma : more than meets the eye ?

J Nucl Med. 2017 Dec 07;:

Authors: Oyen WJG, Jones C

PMID: 29217735 [PubMed - as supplied by publisher]




In vivo imaging of pro- and anti-tumoral cellular components of the tumor microenvironment.
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In vivo imaging of pro- and anti-tumoral cellular components of the tumor microenvironment.

J Nucl Med. 2017 Dec 07;:

Authors: Helfen A, Roth J, Ng T, Eisenblaetter M

Abstract
Tumor development and growth as well as metastatic spread are strongly influenced by various, mostly innate, immune cells, which are recruited to the tumor site and driven to establish a specific tumor-supportive microenvironment. The contents of this microenvironment such as myeloid cells are a major factor for the overall prognosis of malignant disease, addressed by a constantly growing armament of therapeutic interventions, targeting tumor-supportive immune cells. Current clinical imaging has long ignored the growing need for diagnostic approaches addressing these microenvironmental contents, enabling a sensitive and specific classification of tumor immune crosstalk and resulting tumor-associated immune cell activity. In this focus article, we review the present status and promising developments of in vivo molecular imaging approaches of tumor immune components, designed to allow for inference on the cross-talk between tumor cells and the immune system. Based on the infiltrating cell types current imaging modalities are briefly discussed.

PMID: 29217734 [PubMed - as supplied by publisher]




Sex as a Biological Variable in Preclinical Imaging Research: Initial Observations with 18F-Fluorothymidine.
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Sex as a Biological Variable in Preclinical Imaging Research: Initial Observations with 18F-Fluorothymidine.

J Nucl Med. 2017 Dec 07;:

Authors: Chan SR, Salem K, Jeffery J, Powers GL, Yan Y, Shoghi KI, Mahajan AM, Fowler AM

Abstract
The study objective was to investigate whether sex influences 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) uptake and tissue distribution in mouse models of cancer. Methods:18F-FLT biodistribution was measured in three strains of male and female mice (129S6/SvEv, athymic nude, and BALB/c). 18F-Fluoro-2-deoxy-2-D-glucose (18F-FDG) biodistribution was performed for comparison. 18F-FLT uptake was also measured in female 129S6/SvEv mice bearing estrogen-dependent SSM3 mouse mammary tumors, male athymic nude mice bearing androgen-dependent CWR22 prostate cancer xenografts, and male and female athymic nude mice bearing estrogen-independent MDA-MB-231 human breast cancer xenografts. Ki67 expression was assayed by immunohistochemistry. Positron emission tomography/computed tomography (PET/CT) imaging was performed to visualize 18F-FLT biodistribution and for pharmacokinetics. Results: Greater 18F-FLT activity was observed in blood, liver, muscle, heart, kidney, and bone in female mice compared to males. Pharmacokinetic analysis demonstrated early increased renal 18F-FLT activity and greater accumulation of 18F-FLT in the urinary bladder in male mice compared with females. The differential pattern of 18F-FLT biodistribution between the sexes seen with 18F-FLT was not observed with 18F-FDG. Increased tumoral 18F-FLT uptake compared with muscle was observed in both the SSM3 mammary tumors (2.4±0.17 vs 1.6±0.14%ID/g at 2 h post-injection, P = 0.006) and CWR22 prostate cancer xenografts (0.34±0.08 vs 0.098±0.033%ID/g at 2 h post-injection, P = 0.03). However, due to higher nonspecific muscle uptake in female mice, tumor-to-muscle (T:M) uptake ratios were greater for CWR22 tumors compared with SSM3 tumors (4.2±0.78 vs 1.5±0.049 at 2 h post-injection, P = 0.008). Sex-dependent differences in 18F-FLT uptake was also observed for MDA-MB-231 xenografts (T:M ratios 7.2±0.9 female vs 16.9±8.6 male; P = 0.039) . Conversely, greater tumoral Ki67 staining was observed in female mice (71±3% female vs 54±2% male; P = 0.009) which more closely matched the relative differences in absolute 18F-FLT tumor uptake values (4.5±0.99%ID/g female vs 1.9±0.30%ID/g male; P = 0.03). Conclusion: Depending on whether female or male mice are used, differences in biodistribution and nonspecific tissue uptake can adversely impact quantitative measures of 18F-FLT uptake. Thus, sex is a potential variable to consider in defining quantitative imaging metrics using 18F-FLT to assess tumor proliferation.

PMID: 29217733 [PubMed - as supplied by publisher]