UNLABELLED: The lymphatic system plays a critical role in the maintenance of healthy tissues. Its function is an important indicator of the presence and extent of disease. In oncology, metastatic spread to local lymph nodes (LNs) is a strong predictor of poor outcome. Clinical methods for the visualization of LNs involve regional injection and tracking of (99m)Tc-sulfur colloid ((99m)Tc-SC) along with absorbent dyes. Intraoperatively, these techniques suffer from the requirement of administration of multiple contrast media ((99m)Tc-SC and isosulfan blue), unwieldy γ-probes, and a short effective surgical window for dyes. Preclinically, imaging of transport through the lymphatics is further hindered by the resolution of lymphoscintigraphy and SPECT. We investigated multimodal imaging in animal models using intradermal administration of (18)F-FDG for combined diagnostic and intraoperative use. PET visualizes LNs with high sensitivity and resolution and low background. Cerenkov radiation (CR) from (18)F-FDG was evaluated to optically guide surgical resection of LNs. METHODS: Imaging of (18)F-FDG uptake used PET and sensitive luminescent imaging equipment (for CR). Dynamic PET was performed in both sexes and multiple strains (NCr Nude, C57BL/6, and Nu/Nu) of mice. Biodistribution confirmed the uptake of (18)F-FDG and was compared with that of (99m)Tc-SC. Verification of uptake and the ability to use (18)F-FDG CR to guide nodal removal were confirmed histologically. RESULTS: Intradermal injection of (18)F-FDG clearly revealed lymphatic vessels and LNs by PET. Dynamic imaging revealed rapid and sustained labeling of these structures. Biodistribution of the radiotracer confirmed the active transport of radioglucose in the lymphatics to the local LNs and over time into the general circulation. (18)F-FDG also enabled visualization of LNs through CR, even before surgically revealing the site, and guided LN resection. CONCLUSION: Intradermal (18)F-FDG can enhance the preclinical investigation of the lymphatics through dynamic, high-resolution, and quantitative tomographic imaging. Clinically, combined PET/Cerenkov imaging has significant potential as a single-dose, dual-modality tracer for diagnostics (PET/CT) and guided resection of LNs (Cerenkov optical).
UNLABELLED: The lymphatic system plays a critical role in the maintenance of healthy tissues. Its function is an important indicator of the presence and extent of disease. In oncology, metastatic spread to local lymph nodes (LNs) is a strong predictor of poor outcome. Clinical methods for the visualization of LNs involve regional injection and tracking of (99m)Tc-sulfur colloid ((99m)Tc-SC) along with absorbent dyes. Intraoperatively, these techniques suffer from the requirement of administration of multiple contrast media ((99m)Tc-SC and isosulfan blue), unwieldy γ-probes, and a short effective surgical window for dyes. Preclinically, imaging of transport through the lymphatics is further hindered by the resolution of lymphoscintigraphy and SPECT. We investigated multimodal imaging in animal models using intradermal administration of (18)F-FDG for combined diagnostic and intraoperative use. PET visualizes LNs with high sensitivity and resolution and low background. Cerenkov radiation (CR) from (18)F-FDG was evaluated to optically guide surgical resection of LNs. METHODS: Imaging of (18)F-FDG uptake used PET and sensitive luminescent imaging equipment (for CR). Dynamic PET was performed in both sexes and multiple strains (NCr Nude, C57BL/6, and Nu/Nu) of mice. Biodistribution confirmed the uptake of (18)F-FDG and was compared with that of (99m)Tc-SC. Verification of uptake and the ability to use (18)F-FDG CR to guide nodal removal were confirmed histologically. RESULTS: Intradermal injection of (18)F-FDG clearly revealed lymphatic vessels and LNs by PET. Dynamic imaging revealed rapid and sustained labeling of these structures. Biodistribution of the radiotracer confirmed the active transport of radioglucose in the lymphatics to the local LNs and over time into the general circulation. (18)F-FDG also enabled visualization of LNs through CR, even before surgically revealing the site, and guided LN resection. CONCLUSION: Intradermal (18)F-FDG can enhance the preclinical investigation of the lymphatics through dynamic, high-resolution, and quantitative tomographic imaging. Clinically, combined PET/Cerenkov imaging has significant potential as a single-dose, dual-modality tracer for diagnostics (PET/CT) and guided resection of LNs (Cerenkov optical).
Authors: D Albo; J D Wayne; K K Hunt; T F Rahlfs; S E Singletary; F C Ames; B W Feig; M I Ross; H M Kuerer Journal: Am J Surg Date: 2001-10 Impact factor: 2.565
Authors: C M Balch; A C Buzaid; S J Soong; M B Atkins; N Cascinelli; D G Coit; I D Fleming; J E Gershenwald; A Houghton; J M Kirkwood; K M McMasters; M F Mihm; D L Morton; D S Reintgen; M I Ross; A Sober; J A Thompson; J F Thompson Journal: J Clin Oncol Date: 2001-08-15 Impact factor: 44.544
Authors: Mukesh G Harisinghani; Jelle Barentsz; Peter F Hahn; Willem M Deserno; Shahin Tabatabaei; Christine Hulsbergen van de Kaa; Jean de la Rosette; Ralph Weissleder Journal: N Engl J Med Date: 2003-06-19 Impact factor: 91.245
Authors: Bradley J Beattie; Daniel L J Thorek; Charles R Schmidtlein; Keith S Pentlow; John L Humm; Andreas H Hielscher Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240
Authors: E Kriehuber; S Breiteneder-Geleff; M Groeger; A Soleiman; S F Schoppmann; G Stingl; D Kerjaschki; D Maurer Journal: J Exp Med Date: 2001-09-17 Impact factor: 14.307
Authors: Adam K Glaser; Rongxiao Zhang; Jacqueline M Andreozzi; David J Gladstone; Brian W Pogue Journal: Phys Med Biol Date: 2015-08-13 Impact factor: 3.609
Authors: Jennifer J Mueller; Lawrence T Dauer; Rajmohan Murali; Alexia Iasonos; Neeta Pandit-Taskar; Nadeem R Abu-Rustum; Jan Grimm Journal: J Nucl Med Date: 2020-01-10 Impact factor: 10.057
Authors: Gabriel E Büchel; Brandon Carney; Travis M Shaffer; Jun Tang; Christine Austin; Manish Arora; Brian M Zeglis; Jan Grimm; Jörg Eppinger; Thomas Reiner Journal: ChemMedChem Date: 2016-07-29 Impact factor: 3.466
Authors: Gabriel E Büchel; Brandon Carney; Jun Tang; Brian M Zeglis; Jörg Eppinger; Thomas Reiner Journal: J Vis Exp Date: 2017-03-09 Impact factor: 1.355
Authors: Eric W Price; Brian M Zeglis; Jacqueline F Cawthray; Caterina F Ramogida; Nicholas Ramos; Jason S Lewis; Michael J Adam; Chris Orvig Journal: J Am Chem Soc Date: 2013-08-15 Impact factor: 15.419
Authors: Robert W Holloway; Nadeem R Abu-Rustum; Floor J Backes; John F Boggess; Walter H Gotlieb; W Jeffrey Lowery; Emma C Rossi; Edward J Tanner; Rebecca J Wolsky Journal: Gynecol Oncol Date: 2017-05-28 Impact factor: 5.482