title: Feasibility study of the optical imaging of a breast cancer lesion labeled with upconversion nanoparticle biocomplexes.
abstract: Innovative luminescent nanomaterials, termed upconversion nanoparticles (UCNPs), have demonstrated considerable promise as molecular probes for high-contrast optical imaging in cells and small animals. The feasibility study of optical diagnostics in humans is reported here based on experimental and theoretical modeling of optical imaging of an UCNP-labeled breast cancer lesion. UCNPs synthesized in-house were surface-capped with an amphiphilic polymer to achieve good colloidal stability in aqueous buffer solutions. The scFv4D5 mini-antibodies were grafted onto the UCNPs via a high-affinity molecular linker barstar:barnase (Bs:Bn) to allow their specific binding to the human epidermal growth factor receptor HER2/neu, which is overexpressed in human breast adenocarcinoma cells SK-BR-3. UCNP-Bs:Bn-scFv4D5 biocomplexes exhibited high-specific immobilization on the SK-BR-3 cells with the optical contrast as high as 10:1 benchmarked against a negative control cell line. Breast cancer optical diagnostics was experimentally modeled by means of epi-luminescence imaging of a monolayer of the UCNP-labeled SK-BR-3 cells buried under a breast tissue mimicking optical phantom. The experimental results were analyzed theoretically and projected to in vivo detection of early-stage breast cancer. The model predicts that the UCNP-assisted cancer detection is feasible up to 4 mm in tissue depth, showing considerable potential for diagnostic and image-guided surgery applications.
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Grebenik
authors.forename: Annemarie
authors.initials: A
authors.lastname: Nadort
authors.forename: Alla N
authors.initials: AN
authors.lastname: Generalova
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Nechaev
authors.forename: Varun K A
authors.initials: VK
authors.lastname: Sreenivasan
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Khaydukov
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Semchishen
authors.forename: Alexey P
authors.initials: AP
authors.lastname: Popov
authors.forename: Viktor I
authors.initials: VI
authors.lastname: Sokolov
authors.forename: Aleksandr S
authors.initials: AS
authors.lastname: Akhmanov
authors.forename: Vitali P
authors.initials: VP
authors.lastname: Zubov
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Klinov
authors.forename: Vladislav Y
authors.initials: VY
authors.lastname: Panchenko
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Deyev
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Zvyagin
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D049408:Luminescent Agents / Q000737:chemistry; D008954:Models, Biological; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D019047:Phantoms, Imaging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D007136:Immunoglobulins; D049408:Luminescent Agents; D015335:Molecular Probes; D018719:Erb-b2 Receptor Tyrosine Kinases; C081296:Minibody (WT); C508053:ERBB2 protein, human