Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

Deep Hathi, Haiying Zhou, Alex Bollerman-Nowlis, Monica Shokeen, Walter J. Akers

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

Original languageEnglish
Title of host publicationReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VIII
EditorsRamesh Raghavachari, Samuel Achilefu
PublisherSPIE
ISBN (Electronic)9781628419573
DOIs
StatePublished - Jan 1 2016
EventReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VIII - San Francisco, United States
Duration: Feb 15 2016Feb 16 2016

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume9723
ISSN (Print)1605-7422

Conference

ConferenceReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VIII
CountryUnited States
CitySan Francisco
Period02/15/1602/16/16

Keywords

  • FACS
  • bone marrow
  • cd49a
  • integrin receptor
  • multiple myeloma

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  • Cite this

    Hathi, D., Zhou, H., Bollerman-Nowlis, A., Shokeen, M., & Akers, W. J. (2016). Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe. In R. Raghavachari, & S. Achilefu (Eds.), Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VIII [972304] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 9723). SPIE. https://doi.org/10.1117/12.2209662