Chair's Summary (2009)

Imaging of molecular signatures of speciﬁc structures, functions,and pathological alterations in the lung tissue represents animportant and challenging goal. This summary outlines generalthemes of the 24th annual Transatlantic Airway Conferencethat took place in Lucerne in January 2009 focused on thissubject. The following papers presented by the speakers outlinespeciﬁc subjects discussed at the meeting, including identiﬁca-tion of candidate molecular signatures, design of imagingprobes, and application of speciﬁc imaging modalities forvisualization of pulmonary molecular signatures.Noninvasive, real-time visualizationof speciﬁc signs (markers)of physiologic and pathologic processes in the chest immenselyenhances our ability to study, diagnose, and treat lung diseases.Pulmonary imaging, ﬁrst established using Roentgen’s X-rays,has diversiﬁed over the course of the last century to include anarsenal of imaging modalities such as X-ray computed tomog-raphy (CT), nuclear medicine positron emission tomography(PET) and single photon emission computed tomography(SPECT), optical imaging, and magnetic resonance imaging(MRI). One can now visualize structural information about thechest and lungs in addition to functional and molecular changesof diverse parameters. These include perfusion, ventilation,metabolism, tissue density, cell surface expression markers, andenzyme activity. Undoubtedly, the visual information providedat the structural, functional, and molecular levels by thesemodalities provides invaluable tools for evaluating the statusof normal and diseased lungs in both experimental and clinicalsettings.The extraordinary achievements in pulmonary imaging onlyreinforce the need for a discussion on the visualization of targetmolecular signatures in the lungs. ‘‘Target molecular signa-tures’’ are molecules that may serve as speciﬁc markers ofselected elements of tissue structures, and of physiologic orpathologic processes. Figure 1 provides selected examples ofsuch structures (cells and their compartments, components ofextracellular milieu, blood components), functions (cell pertur-bations, enzymatic activity, ventilation, and perfusion), andabnormalities (metabolic changes, neo-antigens and neo-epitopes,activation and translocation of nuclear factors, and nucleic acidchanges).The imaging of molecular signatures will enhance the pre-cision of differential diagnoses of pathologies that are otherwiseindistinguishable by current diagnostic tests, and improveprognoses by stratifying the disease stage and the responsive-ness to treatment. With imaging technologies we can ultimatelyimprove the management of lung diseases and usher in a newtype of ‘‘individualized medicine.’’ Imaging molecular signa-tures in small animal models assists in studying the mecha-nisms of pulmonary physiology and pathology. Furthermore,small animal imaging can guide the translational aspects of basicbench research by validating new therapeutics, diagnostics, oranimal models of human disease. It is thus appropriate andtimely that the organizers of the conference deﬁned its topicas ‘‘Imaging Pulmonary Pathology and Target Molecular Signa-tures.’’Identiﬁcation and visualization of target molecular signa-tures requires efforts in diverse biomedical areas using numer-ous strategies (Figure 2). This subject transcends boundaries ofmany disciplines in biomedical, engineering, chemical, bio-engineering, computer, and physical sciences. The conferencebrought together experts from many of these areas, bothclinicians and basic researchers, to educate each other, redeﬁnethe current status of the subject, and establish new interdisci-plinary collaborations. The meeting focused on three topics:(1) identiﬁcation of the pulmonary target molecular signatures,(2) design of imaging probes and their delivery to the targets,and (3) imaging modalities for visualization of pulmonarytarget molecular signatures. However, for the sake of focus(or ‘‘in the interest of time’’), some aspects of the challenges ofthe ﬁeld (i.e., probe design, chemistry of isotope/emitterintroduction onto probe, development of instrumentation forimaging, and image analysis) were rather tangentially discussedat the meeting.IDENTIFICATION OF MOLECULAR SIGNATURES ANDEXPERIMENTAL APPROACHES FOR THEIR IMAGINGIn his introductory lecture, Dr. Piwnica-Worms provided anoverview of optical and radioisotope imaging of molecules andtheir interactions in living cells and laboratory animals, andgave examples of their applications in the pulmonary imaging(see article by Dothager and Piwnica-Worms, pages 403–410,this issue). Many speakers throughout the conference providedparticular examples of prospective pulmonary target molecularsignatures. Both intracellular (e.g., nucleic acids, enzymes, andtheir substrates) and extracellular (e.g., components of thecellular milieu as well as membrane proteins, sugars, andphospholipids) molecules may serve as molecular targets andsignatures for imaging (1, 2). Drugs, drug carriers, and othernanometer- and micron-scale objects (e.g., environmental pol-lutants and particles) delivered to the lungs via airway orvascular routes, and the physiologic effects caused by theseinterventions, also represent important targets for visualization(3–5) (see also articles by Dolovich, pages 477–485, and Zhangand colleagues, pages 450–457, this issue).Speciﬁc probes recognizing molecular targets or their speciﬁcmicroenvironment include nucleic acids, peptides, enzyme sub-strates, aptamers, sugars, metabolic probes, and a variety ofafﬁnity ligands including antibodies and their fragments. Probescan be labeled with speciﬁc agents that permit optical (lumi-nescence, ﬂuorescence, or near infrared), nuclear medicine(SPECT or PET isotopes), or MRI (e.g., gadolinium) imaging(foroverviews, see articles by Ntziachristos,pages 416–418,Divgi,pages 464–468, Blankenberg, pages 469–476, and Kauczor andcolleagues, pages 458–463, this issue). In an optimal scenario,these probes are activated locally as a result of interaction withthe target or accessory molecules. Speciﬁc protease cleavage of