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Research, Research, otherwise we are lost!
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Research, Research, otherwise we are lost!

J Nucl Med. 2018 Jan 11;:

Authors: Ekmekcioglu O

PMID: 29326363 [PubMed - as supplied by publisher]




[18F]PBR111 PET Imaging in Healthy Controls and Schizophrenia: Test - Retest Reproducibility and Quantification of Neuroinflammation.
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[18F]PBR111 PET Imaging in Healthy Controls and Schizophrenia: Test - Retest Reproducibility and Quantification of Neuroinflammation.

J Nucl Med. 2018 Jan 11;:

Authors: Ottoy J, De Picker L, Verhaeghe J, Deleye S, Wyffels L, Kosten L, Sabbe B, Coppens V, Timmers M, Van Nueten L, Ceyssens S, Stroobants S, Morrens M, Staelens S

Abstract
Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation positron emission tomography (PET) ligand that specifically binds the TSPO, allowing in-vivo visualization and quantification of neuroinflammation. The aim of this study is to evaluate if the test-retest variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F-PBR111 scans were obtained in 17 healthy male controls (HC) and 11 male schizophrenia patients during a psychotic episode (SP). Prior genotyping for the rs6917 polymorphism distinguished high- (HAB) and mixed-affinity binders (MAB). Total volume of distribution (VT) was determined from two-tissue compartment modeling with vascular trapping and a metabolite-corrected plasma input function. A subgroup of HCs (n = 12; 4 HAB and 8 MAB) was scanned twice to assess absolute test-retest variability and intraclass correlation coefficients (ICC) of the regional VT values. Differences in TSPO binding between HC and SP were assessed using mixed model analysis adjusting for age, genotype and age*cohort. The effect of using different scan durations (VT-60min versus VT-90min) was determined based on Pearson's r. Data was presented as mean ± SD. Results: Mean absolute variability in VT ranged from 16 ± 14% (19 ± 20% HAB; 15 ± 11% MAB) in the cortical gray matter to 22 ± 15% (23 ± 15% HAB; 22 ± 16% MAB) in the hippocampus. ICCs were consistently between 0.64 - 0.82 for all tested regions. TSPO binding in SP compared to HC depended on age (cohort*age: P < 0.05) and was increased by +14 ± 4% over the regions. There was a significant effect of genotype on TSPO binding, and VT of HABs was 30 ± 8% (HC: 17 ± 5%, SP: 55 ± 13%) higher than MABs. Across all clinical groups, VT-60min and VT-90min were strongly correlated (r > 0.7, P < 0.0001). Conclusion:18F-PBR111 can be used for monitoring of TSPO binding, as shown by medium test-retest variability and reliability of VT in HCs. Microglial activation is present in SPs depending on age and needs to be adjusted for genotype.

PMID: 29326362 [PubMed - as supplied by publisher]




Molecular Imaging of Bacteria in Patients is an Attractive Fata Morgana, Not a Realistic Option.
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Molecular Imaging of Bacteria in Patients is an Attractive Fata Morgana, Not a Realistic Option.

J Nucl Med. 2018 Jan 11;:

Authors: Hess S, Alavi A, Werner T, Høilund-Carlsen PF

PMID: 29326361 [PubMed - as supplied by publisher]




ImmunoPET in inflammatory bowel disease: Imaging CD4+ T cells in a murine model of colitis.
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ImmunoPET in inflammatory bowel disease: Imaging CD4+ T cells in a murine model of colitis.

J Nucl Med. 2018 Jan 11;:

Authors: Freise AC, Zettlitz KA, Salazar FB, Tavaré R, Tsai WK, Hadjioannou A, Rozengurt N, Braun J, Wu AM

Abstract
Inflammatory bowel diseases (IBD) in humans are characterized in part by aberrant CD4+ T cell responses. Currently, identification of foci of inflammation within the gut requires invasive procedures such as colonoscopy and biopsy. Molecular imaging with antibody fragment probes could be used to noninvasively monitor cell subsets causing intestinal inflammation. Here, GK1.5 cys-diabody (cDb), an anti-mouse CD4 antibody fragment derived from the GK1.5 hybridoma, was used as a positron emission tomography (PET) probe for CD4+ T cells in the dextran sulfate sodium (DSS) mouse model of IBD. METHODS: The DSS mouse model of IBD was validated by assessing changes in CD4+ T cells in the spleen and mesenteric lymph nodes (MLN) using flow cytometry. Furthermore, CD4+ T cell infiltration in the colons of colitic mice was evaluated using immunohistochemistry. 89Zr-labelled GK1.5 cDb was used to image distribution of CD4+ T cells in the abdominal region and lymphoid organs of mice with DSS-induced colitis. Region of interest (ROI) analysis was performed on specific regions of the gut to quantify probe uptake. Colons, ceca, and MLN were removed and imaged ex vivo by PET. Imaging results were confirmed by ex vivo biodistribution analysis. RESULTS: Increased number of CD4+ T cells in colons of colitic mice was confirmed by anti-CD4 immunohistochemistry. Increased uptake of 89Zr-malDFO-GK1.5 cDb in the distal colon of colitic mice was visible in vivo in PET scans, and ROI analysis of the distal colon confirmed increased activity in DSS mice. MLN from colitic mice were enlarged and visible in PET images. Ex vivo scans and biodistribution confirmed higher uptake in DSS-treated colons (DSS: 1.8±0.40, control: 0.45±0.12 % injected dose (ID)/organ respectively), ceca (DSS: 1.1±0.38, control: 0.35±0.09 % ID/organ), and MLN (DSS: 1.1±0.58, control: 0.37±0.25 % ID/organ). CONCLUSION:89Zr-malDFO-GK1.5 cDb detected CD4+ T cells in the colons, ceca, and MLN of colitic mice, and could prove useful for further investigations of CD4+ T cells in preclinical models of IBD, with potential to guide development of antibody-based imaging in human IBD.

PMID: 29326360 [PubMed - as supplied by publisher]




Doxorubicin Effect on Myocardial Metabolism as a Prerequisite for Subsequent Development of Cardiac Toxicity: are there unsuspecting confounders?
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Doxorubicin Effect on Myocardial Metabolism as a Prerequisite for Subsequent Development of Cardiac Toxicity: are there unsuspecting confounders?

J Nucl Med. 2018 Jan 11;:

Authors: Finessi M, Nicolotti DG, Bisi G, Deandreis D

PMID: 29326359 [PubMed - as supplied by publisher]




Targeted Alpha Therapy of mCRPC with 225Actinium-PSMA-617: Swimmer-Plot analysis suggests efficacy regarding duration of tumor-control.
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Targeted Alpha Therapy of mCRPC with 225Actinium-PSMA-617: Swimmer-Plot analysis suggests efficacy regarding duration of tumor-control.

J Nucl Med. 2018 Jan 11;:

Authors: Kratochwil C, Bruchertseifer F, Rathke H, Hohenfellner M, Giesel FL, Haberkorn U, Morgenstern A

Abstract
The aim of this evaluation is to identify first indicators regarding the efficacy of 225Ac-PSMA-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with 3 cycles of 100 kBq/kgBW 225Ac-PSMA-617 in 2 months intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Prostate-specific membrane antigen (PSMA)-PET/CT or PSMA-SPECT/CT were used for baseline staging and imaging follow-up at month six. Follow-up included duration of PSA-response and radiological progression free survival at month six. Patient histories were reviewed for the duration of previous treatment lines and a Swimmer-Plot was used to intra-individually compare the duration of tumor control by PSMA-therapy vs. prior treatment modalities. Results: 31 of 40 patients were treated per protocol. 5 patients discontinued due to non-response, 4 patients due to xerostomia. In patients surviving at least eight weeks, a PSA decline >50% was observed in 24/38 (63%) and any PSA response in 33/38 (87%) of patients. Median duration of tumor-control under 225Ac-PSMA-617 last-line therapy was 9.0 months; 5 patients presented with enduring responses of > 2 years. As all patients had very advanced disease this compares favorably with the tumor-control rates associated with earlier phase disease; the most common preceding 1st, 2nd, 3rd and 4th line therapies were abiraterone (median duration 10.0 months), docetaxel (6.5 months), enzalutamide (6.5 months) and cabazitaxel (6.0 months). Conclusion: Positive response of surrogate parameters demonstrates remarkable anti-tumor activity of 225Actinium-PSMA-617. Swimmer-plot analysis indicates promising duration of tumor-control, especially taking into account the unfavorable prognostic profile of the selected advanced-stage patients. Xerostomia was the main reason to discontinue therapy or to refuse additional administrations and was in the same dimension as non-response; this indicates that further modifications of the treatment regimen with regard to side effects might be necessary to further enhance the therapeutic range.

PMID: 29326358 [PubMed - as supplied by publisher]




Gauging cardiac repair and regeneration with new molecular probes.
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Gauging cardiac repair and regeneration with new molecular probes.

J Nucl Med. 2018 Jan 11;:

Authors: Thackeray JT, Bengel FM

PMID: 29326357 [PubMed - as supplied by publisher]




Cerebrospinal Fluid, Hyposmia and Dementia in Alzheimer Disease: Insights from Dynamic PET and a Hypothesis.
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Cerebrospinal Fluid, Hyposmia and Dementia in Alzheimer Disease: Insights from Dynamic PET and a Hypothesis.

J Nucl Med. 2018 Jan 11;:

Authors: Kumaria A

PMID: 29326356 [PubMed - as supplied by publisher]




18F-FEDAC as a targeting agent for activated macrophages in DBA/1 mice with collagen-induced arthritis: Comparison with 18F-FDG.
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18F-FEDAC as a targeting agent for activated macrophages in DBA/1 mice with collagen-induced arthritis: Comparison with 18F-FDG.

J Nucl Med. 2018 Jan 11;:

Authors: Chung SJ, Yoon HJ, Cheon GJ, Youn H, Kim MJ, Xie L, Lee YS, Jeong JM, Chung JK, Kang KW, Zhang MR

Abstract
Activated macrophages have been known to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). 18F-FEDAC is a radiolabeled ligand for the translocator protein (TSPO), which is abundant in activated macrophages. We evaluated the feasibility of 18F-FEDAC in a murine RA model. Methods: RAW 264.7 mouse macrophages were activated by lipopolysaccharide. TSPO expression levels in activated and inactivated macrophages were measured by quantitative polymerase chain reaction (qPCR) and western blotting. The cellular uptake and specific binding of 18F-FEDAC were measured using a gamma counter. For the in vivo study, collagen-induced arthritis (CIA) was developed in DBA/1 mice and the clinical score for arthritis was measured regularly. 18F-FEDAC and 18F-FDG positron emission tomography (PET) images were acquired on days 23 and 37 after first immunization. Histological examinations were performed to evaluate macrophages and TSPO expression. Results: We found increased TSPO mRNA and protein expression in activated macrophages. Uptake of 18F-FEDAC in activated macrophages was higher than that in non-activated cells, and was successfully blocked by the competitor PK11195. In CIA mice, joint swelling was apparent on day 26 after the first immunization and the condition worsened by day 37. 18F-FEDAC uptake by arthritic joints increased early on (day 23), whereas 18F-FDG uptake did not. However, 18F-FDG uptake by arthritic joints markedly increased at later stages (day 37) to a higher level than 18F-FEDAC uptake. The 18F-FEDAC uptake was weakly correlated with summed clinical severity score (P = 0.019, r=0.313), whereas the 18F-FDG uptake was strongly correlated with summed severity score (p<0.001, r=0.897). Histologic sections of arthritic joints demonstrated an influx of macrophages compared to that in normal joints. Conclusion:18F-FEDAC enabled the visualization of active inflammation sites in arthritic joints in a CIA model by targeting TSPO expression in activated macrophages. The results suggest the potential usefulness of 18F-FEDAC imaging in early phase of RA.

PMID: 29326355 [PubMed - as supplied by publisher]




ACCURACY OF DOSE CALIBRATORS FOR GALLIUM-68 PET IMAGING: UNEXPECTED FINDINGS IN A MULTI-CENTRE CLINICAL PRE-TRIAL ASSESSMENT.
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ACCURACY OF DOSE CALIBRATORS FOR GALLIUM-68 PET IMAGING: UNEXPECTED FINDINGS IN A MULTI-CENTRE CLINICAL PRE-TRIAL ASSESSMENT.

J Nucl Med. 2018 Jan 11;:

Authors: Bailey DL, Hofman MS, Forwood NJ, O'Keefe GJ, Scott AM, van Wyngaardt WM, Howe B, Kovacev O, Francis RJ

Abstract
AIMS: We report the discovery of a systematic miscalibration during the work-up process for site validation of a multi-centre clinical PET imaging trial using 68Ga, which manifested as a consistent and reproducible underestimation in the quantitative accuracy (assessed by SUV) of a range of PET cameras from different manufacturers at a number of different facilities around Australia. METHODS: Sites were asked to follow a strict preparation protocol to create a radioactive phantom with 68Ga to be imaged using a standard clinical protocol prior to commencing imaging in the trial. All sites had routinely used 68Ga for clinical PET imaging for many years. The reconstructed image data were transferred to an imaging core laboratory for analysis, along with information about ancillary equipment such as the radionuclide dose calibrator. Fourteen PET systems were assessed from ten nuclear medicine facilities in Australia with the aim for each PET camera being to produce images within ±5% of the true SUV value. RESULTS: At initial testing, 10 of the 14 PET systems underestimated the SUV by 15% on average (range -13% - -23%). Multiple PET cameras at one site, from two different manufacturers, were all similarly affected, suggesting a common cause. We eventually identified an incorrect factory-shipped dose calibrator setting from a single manufacturer as being the cause. The calibrator setting for 68Ga was subsequently adjusted by the users so that the reconstructed images produced accurate values. CONCLUSION: PET imaging involves a chain of measurements and calibrations to produce accurate quantitative performance. Testing of the entire chain can, however, be simply performed and should form part of any quality assurance (QA) programme or pre-qualifying site assessment prior to commencing a quantitative imaging trial or clinical imaging.

PMID: 29326354 [PubMed - as supplied by publisher]