title: Molecular imaging agents specific for the annulus fibrosus of the intervertebral disk.
abstract: Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM) fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Summer L
authors.initials: SL
authors.lastname: Gibbs-Strauss
authors.forename: Carrie
authors.initials: C
authors.lastname: Vooght
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Fish
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Nasr
authors.forename: Tiberiu M
authors.initials: TM
authors.lastname: Siclovan
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Barnhardt
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Tan Hehir
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology*; D017116:Low Back Pain / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000473:pathology; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes