title: Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage.
abstract: Lung deep lymphatic drainage (LDLD) plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry. Lung deep lymphatic chains (LDLC) constitute one of the first sites of lung tumours' dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies. Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC. Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes.
  
  
  CONCLUSIONS
  the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes.
authors.affiliation: Instituto de Biofísica e Biomatemática, Faculdade de Medicina, Universidade de Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal. filomena@ibili.uc.pt
authors.forename: Maria Filomena
authors.initials: MF
authors.lastname: Rabaça Roque Botelho
authors.forename: Maria Alcide
authors.initials: MA
authors.lastname: Tavares Marques
authors.forename: Célia Maria
authors.initials: CM
authors.lastname: Freitas Gomes
authors.forename: Augusto
authors.initials: A
authors.lastname: Marques Ferreira da Silva
authors.forename: Vasco António
authors.initials: VA
authors.lastname: Andrade Figueiredo Bairos
authors.forename: Manuel Amaro
authors.initials: MA
authors.lastname: de Matos Santos Rosa
authors.forename: Antero
authors.initials: A
authors.lastname: Pena Abrunhosa
authors.forename: João José
authors.initials: JJ
authors.lastname: Pedroso de Lima
mesh_terms: D000818:Animals; D008081:Liposomes; D008168:Lung; D008196:Lymph / Q000000981:diagnostic imaging*; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000502:physiology*; D008297:Male; D036103:Nanotechnology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D019690:Technetium Tc 99m Exametazime
chemical_list: D008081:Liposomes; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime