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      1. Author :
        Van Elssen, Catharina H. M. J.; Rashidian, Mohammad; Vrbanac, Vladimir; Wucherpfennig, Kai W.; El Habre, Zeina; Sticht, Jana; Freund, Christian; Jacobsen, Johanne; Cragnolini, Juanjo; Ingram, Jessica; Plaisier, Loes; Spierings, Eric; Tager, Andrew M.; Ploegh, Hidde
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animal Imaging; G8 PET; GvHD; Hematology; humanized Mice; ImmunoPET; Pet/Ct; Single domain antibodies
      12. Abstract :
        The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer or auto-immunity. Immuno-PET is a non-invasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets. We aimed to develop a method to noninvasively image human immune responses in a relevant humanized mouse model. We developed a camelid-derived single domain antibody (VHH) specific for human class II MHC products and used it to non-invasively image human immune cell reconstitution in NSG (NOD-scid gamma) mice reconstituted with human fetal thymus, liver and liver-derived hematopoitic stem cells (BLT mice). We show imaging of infiltrating immunocytes in BLT mice that spontaneously develop a graft versus host (GvHD)-like condition, characterized by alopecia, blepharitis and target organ infiltration by activated human T cells. In diseased animals, we show an increased PET signal in the liver, attributable to infiltration of activated Class II MHC-positive T cells. Non-invasive imaging of immune infiltration and activation could thus be of importance for diagnosis and evaluation of treatment of GvHD and holds promise for other diseases characterized by inflammation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/28209904
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        11896
      1. Author :
        Fuchs, Kerstin; Kuehn, Anna; Mahling, Moritz; Guenthoer, Philipp; Hector, Andreas; Hartl, Dominik; Laufer, Stefan; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Reischl, Gerald; Röcken, Martin; Pichler, Bernd J.; Kneilling, Manfred
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; PET; mice
      12. Abstract :
        Hypoxia is essential for the development of autoimmune diseases such as rheumatoid arthritis (RA) and is associated with the expression of reactive oxygen species (ROS), due to enhanced infiltration of immune cells. The aim of this study was to demonstrate the feasibility of measuring hypoxia non-invasively in vivo in arthritic ankles with positron emission tomography (PET)/magnetic resonance imaging (MRI) using the hypoxia tracers 18F-fluoromisonidazole (FMISO) and 18F-fluoroazomycinarabinoside (FAZA). Additionally, we quantified temporal dynamics of hypoxia and ROS stress using L-012, a ROS-sensitive chemiluminescence optical imaging (OI) probe, and analyzed the activation of hypoxia inducible factors (HIFs). Methods: Mice underwent non-invasive in vivo PET/MRI to measure hypoxia or OI to analyze ROS expression. Additionally, we performed ex vivo pimonidazole-/HIF-1α-immunohistochemistry and HIF-1α/2α-western blot/mRNA-analysis of inflamed and healthy ankles to confirm our in vivo results. Results: Mice diseased from experimental RA exhibited a 3-fold enhancement in hypoxia tracer uptake, even in the very early disease stages, and a 45-fold elevation in ROS-expression in inflamed ankles compared with the ankles of healthy controls. We further found strong correlations of our non-invasive in vivo hypoxia PET data with pimonidazole and expression of HIF-1α in arthritic ankles. The strongest hypoxia tracer uptake was observed as soon as day 3, whereas the most pronounced ROS stress was evident on day 6 after the onset of experimental RA, indicating that tissue hypoxia can precede ROS stress in RA. Conclusion: Collectively, for the first time, we have demonstrated that non-invasive measurement of hypoxia in inflammation using 18F-FAZA/18F-FMISO-PET imaging represent a promising new tool for uncovering and monitoring rheumatic inflammation in vivo. Further, as hypoxic inflamed tissues are associated with overexpression of HIFs, specific inhibition of HIFs might represent a new powerful treatment strategy.
      13. URL :
        http://jnm.snmjournals.org/content/early/2017/02/08/jnumed.116.185934.abstract http://jnm.snmjournals.org/content/58/5/853
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13336
      15. Serial :
        14090
      1. Author :
        Hekman, Marlène C.H.; Rijpkema, Mark; Bos, Desirée; Oosterwijk, Egbert; Goldenberg, David M; Mulders, Peter F.A.; Boerman, Otto C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        molecular imaging;; colorectal cancer;; CEA;; labetuzumab;; fluorescence-guided surgery; IVIS; IVIS FLI ex vivo
      12. Abstract :
        Background: Intraoperative dual-modality imaging can help the surgeon distinguish tumor from normal tissue. This technique may prove particularly valuable if small tumors need to be removed that are difficult to detect with the naked eye. The humanized anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody, labetuzumab (hMN-14), can be used as a tumor targeting agent in colorectal cancer (CRC), since CEA is overexpressed in approximately 95% of CRC. Dual-labeled labetuzumab, labeled with both a near-infrared fluorescent dye (IRDye800CW) and a radioactive label (Indium-111), can be used as a tracer for dual-modality imaging. This study aimed to assess whether dual-modality imaging using Indium-111-DTPA-labetuzumab-IRDye800CW can detect pulmonary micrometastases in a mouse model. Methods: Pulmonary GW-39 human colonic carcinoma microcolonies were induced in athymic BALB/c mice by intravenous injection of 100 µL of a GW-39 cell suspension. After 1, 2, 3, and 4 weeks of tumor growth dual-modality imaging was performed 3 days after i.v. injection of Indium-111-DTPA-labetuzumab-IRDye800CW (10 µg, 25 MBq). MicroSPECT/CT images and optical images were acquired and image-guided surgery was performed. Finally, the biodistribution of the dual-labeled tracer was determined. Formalin-fixed sections of the lungs were analyzed using fluorescence imaging, autoradiography and immunohistochemistry. Results: Sub-millimeter pulmonary tumor colonies could be visualized with both microSPECT and fluorescence imaging from the first week of tumor growth, before they became visible with the naked eye. Furthermore, dual-modality imaging could be used to guide resection of tumor lesions. Mean uptake of the dual-labeled tracer in tumor lesions was 17.2 ± 5.4 %ID/g and 16.5 ± 4.4 %ID/g in weeks 3 and 4, respectively. Immunohistochemical analysis of the tumorous lungs showed that the distribution of the radioactive and fluorescent signal co-localized with CEA-expressing tumor lesions. Conclusion: Dual-modality imaging after injection of Indium-111-labetuzumab-IRDye800CW can be used to detect sub-millimeter CEA-expressing pulmonary colonies, before they become visible with the naked eye, supporting the added value of this technique to the resection of small tumor lesions.
      13. URL :
        http://jnm.snmjournals.org/content/early/2017/01/25/jnumed.116.185470.abstract http://jnm.snmjournals.org/content/58/5/706.full.pdf
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13263
      15. Serial :
        14051
      1. Author :
        Wang, Jiahu; Arulanandam, Rozanne; Wassenaar, Richard; Falls, Theresa; Petryk, Julia; Paget, Judith; Garson, Kenneth; Cemeus, Catia; Vanderhyden, Barbara; Wells, Glenn; Bell, john; Le Boeuf, Fabrice
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animal Imaging; Oncology: GI; SPECT/CT; Animal Imaging; Cancer Imaging; Oncolytic Viruses; SPECT/CT; hNIS; hSSR2; IVIS; IVIS BLI in vivo
      12. Abstract :
        Purpose: Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biological agent, oncolytic virus has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in pre-clinical models and in clinical trials. In order to give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral based platforms with two specific gene reporters. Methods: We have incorporated the human sodium iodide symporter (hNIS) and the human somatostatin receptor 2 (hSR) in the vaccinia-based OV and tested viral constructs for their abilities to track and treat tumor development in vivo. Results: Early and high level expression of hNIS is detrimental to the recombinant virus, leading to the aggregation of hNIS protein and early cell death. Putting hNIS under a late synthetic promoter allows a higher functional expression of the protein and much stronger 123I or 99Tc uptake. In vivo, the hNIS-containing virus infects and amplifies in the tumor site, showing a better efficacy than the parental virus. The hNIS expression at the tumor site allows for the imaging of viral infection and tumor regression. Similarly, hSR-containing OV vaccinia infects and lyses cancer cells. Conclusion: When tumor-bearing mice were given hNIS- and hSR-containing OV, radio-isotopes of 99Tc and 111In signals coalesce at the tumor, highlighting the power of using these viruses for tumor diagnosis and treatment.
      13. URL :
        http://jnm.snmjournals.org/content/early/2016/09/13/jnumed.116.180463.abstract
      14. Call Number :
        PKI @ user @ 12500
      15. Serial :
        19409
      1. Author :
        Mellhammar, Emma Matilda; Dahlbom, Magnus; Axelsson, Johan; Strand, Sven-Erik
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Dead time; G4 Pet; Image distortion; Instrumentation; Pet; Pile up; Radionuclide Therapy; X-Ray
      12. Abstract :
        Positron emission tomography (PET) may provide important information on the therapeutic response of radiopharmaceutical therapy (RPT) during therapy. The radiation emission from the RPT radionuclide may disturb the coincidence detection and impair the image resolution. In this study we tested the feasibility to perform intratherapeutic PET on three preclinical PET systems. Methods: Using 22Na point sources and phantoms filled with 18F, and a phantom filled with either 99mTc or 177Lu, the coincidence count rate and the spatial resolution when both a PET and a therapeutic radionuclide were present in the PET camera, were evaluated. 99mTc was used as a substitute for a generic therapeutic radioisotope, since it has a suitable half-life and is easy obtainable. Results: High activities of 99mTc deteriorated the coincidence count rate from the 18F-filled phantom with a 22Na point source on all three systems evaluated. One of the systems could to a high degree correct the count rate with its dead time correction. The spatial resolution was degraded at high activities of 99mTc for all systems. On one of the systems 177Lu increased the coincidence count rate and slightly affected the spatial resolution. The results for high activities of 177Lu were similar to those for 99mTc. Conclusion: Intratherapeutic imaging might be a feasible method to study RPT treatment response. However, some sensitive preclinical PET systems, unable to handle high count rates, suffer count losses and may also introduce image artifacts.
      13. URL :
        http://jnm.snmjournals.org/content/early/2016/07/27/jnumed.116.175539
      14. Call Number :
        PKI @ user @
      15. Serial :
        11764
      1. Author :
        Zhou, Min; Melancon, Marites; Stafford, R. Jason; Li, Junjie; Nick, Alpa M.; Tian, Mei; Sood, Anil K.; Li, Chun
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        57
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS FLI in vivo; PET
      12. Abstract :
        Imaging-based techniques have enabled the direct integration of noninvasive imaging with minimally invasive interventions such as photothermal therapy (PTT) to improve the precision of treatment. Methods: We investigated the feasibility of PTT for ovarian cancer under the guidance of PET and MR temperature imaging using copper sulfide nanoparticles (CuS NPs). The tumor distribution of the CuS NPs after systemic administration was assessed using highly sensitive, quantifiable PET imaging. Two wavelengths of near-infrared (NIR) lasers—808 and 980 nm—were tested for PTT using noninvasive MR temperature imaging real-time monitoring. Results: The in vivo studies revealed that the 980-nm NIR laser had better photothermal effects than the 808-nm NIR laser. These results were in accord with the histologic findings. In vivo PTT using CuS NPs combined with 980-nm laser irradiation achieved significant tumor ablation compared with no treatment control in both subcutaneous (P = 0.007) and orthotopic (P < 0.001) models of ovarian cancer with regard to the percentage of necrotic damage. Conclusion: Our results indicate that real-time monitoring of the accuracy of PTT is a promising approach for future clinical translation of this emerging thermal ablation technique.
      13. URL :
        http://jnm.snmjournals.org/content/57/11/1778.abstract http://jnm.snmjournals.org/content/57/11/1778.long
      14. Call Number :
        PKI @ user @ 12646
      15. Serial :
        19267
      1. Author :
        Witney, Timothy H.; Pisaneschi, Federica; Alam, Israt S.; Trousil, Sebastian; Kaliszczak, Maciej; Twyman, Frazer; Brickute, Diana; Nguyen, Quang-Dé; Schug, Zachary; Gottlieb, Eyal; Aboagye, Eric O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
      6. Products :
      7. Volume :
        55
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Cell Line, Tumor; Fdg; Fluorine Radioisotopes; Fpia; G4 Pet; Humans; Lipid Metabolism; Mice; Neoplasms, Experimental; Pentanoic Acids; Pet; Positron-Emission Tomography; Radiopharmaceuticals; tumor detection; X-Ray
      12. Abstract :
        Deregulated cellular metabolism is a hallmark of many cancers. In addition to increased glycolytic flux, exploited for cancer imaging with (18)F-FDG, tumor cells display aberrant lipid metabolism. Pivalic acid is a short-chain, branched carboxylic acid used to increase oral bioavailability of prodrugs. After prodrug hydrolysis, pivalic acid undergoes intracellular metabolism via the fatty acid oxidation pathway. We have designed a new probe, 3-(18)F-fluoro-2,2-dimethylpropionic acid, also called (18)F-fluoro-pivalic acid ((18)F-FPIA), for the imaging of aberrant lipid metabolism and cancer detection.
        METHODS: Cell intrinsic uptake of (18)F-FPIA was measured in murine EMT6 breast adenocarcinoma cells. In vivo dynamic imaging, time course biodistribution, and radiotracer stability testing were performed. (18)F-FPIA tumor retention was further compared in vivo to (18)F-FDG uptake in several xenograft models and inflammatory tissue.
        RESULTS: (18)F-FPIA rapidly accumulated in EMT6 breast cancer cells, with retention of intracellular radioactivity predicted to occur via a putative (18)F-FPIA carnitine-ester. The radiotracer was metabolically stable to degradation in mice. In vivo imaging of implanted EMT6 murine and BT474 human breast adenocarcinoma cells by (18)F-FPIA PET showed rapid and extensive tumor localization, reaching 9.1% ± 0.5% and 7.6% ± 1.2% injected dose/g, respectively, at 60 min after injection. Substantial uptake in the cortex of the kidney was seen, with clearance primarily via urinary excretion. Regarding diagnostic utility, uptake of (18)F-FPIA was comparable to that of (18)F-FDG in EMT6 tumors but superior in the DU145 human prostate cancer model (54% higher uptake; P = 0.002). Furthermore, compared with (18)F-FDG, (18)F-FPIA had lower normal-brain uptake resulting in a superior tumor-to-brain ratio (2.5 vs. 1.3 in subcutaneously implanted U87 human glioma tumors; P = 0.001), predicting higher contrast for brain cancer imaging. Both radiotracers showed increased localization in inflammatory tissue.
        CONCLUSION: (18)F-FPIA shows promise as an imaging agent for cancer detection and warrants further investigation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/25012458
      14. Call Number :
        PKI @ user @
      15. Serial :
        11783
      1. Author :
        Herrmann, Ken; Dahlbom, Magnus; Nathanson, David; Wei, Liu; Radu, Caius; Chatziioannou, Arion; Czernin, Johannes
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
      6. Products :
      7. Volume :
        54
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        18f-Fdg; Animals; Cell Line, Tumor; Equipment Design; Equipment Failure Analysis; G4 Pet; Mice; Mice, SCID; Miniaturization; Neoplasms, Experimental; Positron-Emission Tomography; preclinical PET; Reproducibility of Results; scanner performance; Sensitivity and Specificity; tumor models; X-Ray
      12. Abstract :
        The Genisys4 is a small bench-top preclinical PET scanner designed to enable imaging in biology, biochemistry, and pharmacology laboratories and imaging centers. Here, we compare its performance with that of a well-established preclinical PET scanner.
        METHODS: Subcutaneous and lung tumor xenografts were used to compare lesion detectability and treatment responses to chemotherapy (gemcitabine) using (18)F-FDG PET. The size of subcutaneous xenografts (L1210 and L1210-10K leukemia cells) and lung metastases (B-16 melanoma cells) was measured on small-animal CT images. Tumor (18)F-FDG uptake was expressed as percentage injected dose per gram. Using list-mode data, serial images of the left ventricular blood pool were used to generate time-activity curves.
        RESULTS: Subcutaneous xenografts (range, 4-12 mm; mean ± SD, 6.1 ± 1.7 mm) and lung metastases (range, 1-5 mm; mean, 2.1 ± 1.2 mm) were detected equally well with both scanners. Tumor (18)F-FDG uptake measured with both scanners was highly correlated for subcutaneous xenografts (r(2) = 0.93) and lung metastases (r(2) = 0.83). The new Genisys4 scanner and the established scanner provided comparable treatment response information (r(2) = 0.93). Dynamic imaging sequences permitted the generation of left ventricular blood-pool time-activity curves with both scanners.
        CONCLUSION: Using subcutaneous and lung xenografts, a novel and an established preclinical PET scanner provided equivalent information with regard to lesion detection, tumor (18)F-FDG uptake, tumor response to treatment, and generation of time-activity curves. Thus, the Genisys4 provides a small, efficient bench-top preclinical PET alternative for quantitatively studying murine tumor models in biology, biochemistry, and pharmacology laboratories and preclinical imaging centers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23628700
      14. Call Number :
        PKI @ user @
      15. Serial :
        11785
      1. Author :
        Robertson, R.; Germanos, M. S.; Manfredi, M. G.; Smith, P. G.; Silva, M. D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Journal of nuclear medicine : official publication, Society of Nuclear Medicine
      6. Products :
      7. Volume :
        52
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents/pharmacology/therapeutic use; Cell Line, Tumor; *Cell Transformation, Neoplastic; Cyclopentanes/*pharmacology/therapeutic use; Female; Fluorodeoxyglucose F18/*diagnostic use; Humans; Luminescent Measurements/*methods; Lymphoma/drug therapy/*pathology/radionuclide imaging; Mice; Molecular Imaging/*methods; Positron-Emission Tomography/*methods; Pyrimidines/*pharmacology/therapeutic use
      12. Abstract :
        Cerenkov luminescence imaging (CLI) is an emerging imaging technique that combines aspects of both optical and nuclear imaging fields. The ability to fully evaluate the correlation and sensitivity of CLI to PET is critical to progress this technique further for use in high-throughput screening of pharmaceutical compounds. To achieve this milestone, it must first be established that CLI data correlate to PET data in an in vivo preclinical antitumor study. We used MLN4924, a phase 2 oncology therapeutic, which targets and inhibits the NEDD8-activating enzyme pathway involved in the ubiquitin-proteasome system. We compared the efficacious effects of MLN4924 using PET and Cerenkov luminescence image values in the same animals. METHODS: Imaging of (18)F-FDG uptake was performed at 5 time points after drug treatment in the subcutaneously implanted diffuse large B-cell lymphoma tumor line OCI-Ly10. Data were acquired with both modalities on the same day, with a 15-min delay between CLI and PET. PET data analysis was performed using percentage injected dose per cubic centimeter of tissue (%ID/cm(3)), average standardized uptake values, and total glycolytic volume. CLI measurements were radiance, radiance per injected dose (radiance/ID), and total radiant volume. RESULTS: A strong correlation was found between PET total glycolytic volume and CLI total radiant volume (r(2) = 0.99) and various PET and CLI analysis methods, with strong correlations found between PET %ID/cm(3) and CLI radiance (r(2) = 0.83) and CLI radiance/ID (r(2) = 0.82). MLN4924 demonstrated a significant reduction in tumor volume after treatment (volume ratio of treated vs. control, 0.114 at day 29). CONCLUSION: The PET and CLI data presented confirm the correlation and dynamic sensitivity of this new imaging modality. CLI provides a preclinical alternative to expensive PET instrumentation. Future high-throughput studies should provide for quicker turnaround and higher cost-to-return benefits in the drug discovery process.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21994410
      14. Call Number :
        PKI @ catherine.lautenschlager @ 6365
      15. Serial :
        8880
      1. Author :
        Lazari, Mark; Collins, Jeffrey; Shen, Bin; Farhoud, Mohammed; Yeh, Daniel; Maraglia, Brandon; Chin, Frederick T.; Nathanson, David A.; Moore, Melissa; van Dam, R. Michael
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        Journal of Nuclear Medicine Technology
      6. Products :
      7. Volume :
        42
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        18f-Fac; 18f-Feau; 18f-Fmau; Animals; automated radiosynthesis; Chemistry Techniques, Synthetic; Chromatography, High Pressure Liquid; Elixys; Female; Fluorodeoxyglucose F18; Mice; Mice, Inbred BALB C; Positron-Emission Tomography; Quality Control; radiochemistry kits; Radiopharmaceuticals; Software; Whole Body Imaging
      12. Abstract :
        Fully automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of PET tracers made under current good manufacturing practice guidelines. There is a current trend toward supporting kitlike disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers because of pressure, temperature, and chemical compatibility considerations. This study demonstrated the versatile use of the ELIXYS fully automated radiosynthesizer to adapt and produce 8 different (18)F-labeled PET tracers of varying complexity.
        METHODS: Three-reactor syntheses of 2-deoxy-2-(18)F-fluoro-β-d-arabinofuranosylcytosine (d-(18)F-FAC), 2-deoxy-2-(18)F-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-(18)F-FMAU), and 2-deoxy-2-(18)F-fluoro-5-ethyl-β-d-arabinofuranosyluracil (d-(18)F-FEAU) along with the 1-reactor syntheses of d-(18)F-FEAU, (18)F-FDG, 3-deoxy-3-(18)F-fluoro-l-thymidine ((18)F-FLT), (18)F-fallypride, 9-(4-(18)F-fluoro-3-hydroxymethylbutyl)-guanine ((18)F-FHBG), and N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB), were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted and slightly modified from those in the literature but were not fully optimized. Furthermore, (18)F-FLT, (18)F-FDG, and (18)F-fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing severe combined immunodeficient mice and wild-type BALB/c mice. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests.
        RESULTS: All tracers were produced with radiochemical yields comparable to those in the literature. (18)F-FLT, (18)F-FDG, and (18)F-fallypride were successfully used to image the mice, with results consistent with those reported in the literature. All tracers that were subjected to clinical quality control tests passed.
        CONCLUSION: The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple (18)F-labeled PET tracers suitable for clinical applications using the same hardware setup.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/25033883
      14. Call Number :
        PKI @ user @
      15. Serial :
        11780
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