Optical Imaging of Mammary and Prostate Tumors in Living Animals using a Synthetic Near Infrared Zinc(II)-Dipicolylamine Probe for Anionic Cell Surfaces

Department of Chemistry and Biochemistry, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 12/2009; 132(1):67-9. DOI: 10.1021/ja908467y
Source: PubMed

ABSTRACT In vivo optical imaging shows that a fluorescent imaging probe, comprised of a near-infrared fluorophore attached to an affinity group containing two zinc(II)-dipicolylamine (Zn-DPA) units, targets prostate and mammary tumors in two different xenograft animal models. The tumor selectivity is absent with control fluorophores whose structures do not have appended Zn-DPA targeting ligands. Ex vivo biodistribution and histological analyses indicate that the probe is targeting the necrotic regions of the tumors, which is consistent with in vitro microscopy showing selective targeting of the anionic membrane surfaces of dead and dying cells.

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Available from: Walter J Akers, Sep 28, 2015
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    • "Others have used the C2A domain of radiolabeled synaptotagmin I for PET and SPECT imaging of lung carcinomas in animals treated with paclitaxel [18,19]. Low molecular weight PS imaging probes, such as dipicolylamine-Zn2+ complexes [20], are also in development. While these probes have demonstrated diagnostic value, they all display unfavorable biodistributions with high abdominal background signal due to probe accumulation in the liver and kidneys. "
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    ABSTRACT: Phosphatidylserine (PS) is an attractive target for imaging agents that identify tumors and assess their response to therapy. PS is absent from the surface of most cell types, but becomes exposed on tumor cells and tumor vasculature in response to oxidative stresses in the tumor microenvironment and increases in response to therapy. To image exposed PS, we used a fully human PS-targeting antibody fragment, PGN635 F(ab')2, that binds to complexes of PS and β2-glycoprotein I. PGN635 F(ab')2 was labeled with the positron-emitting isotope iodine-124 ((124)I) and the resulting probe was injected into nude mice bearing subcutaneous or orthotopic human PC3 prostate tumors. Biodistribution studies showed that (124)I-PGN635 F(ab')2 localized with remarkable specificity to the tumors with little uptake in other organs, including the liver and kidneys. Clear delineation of the tumors was achieved by PET 48 hours after injection. Radiation of the tumors with 15 Gy or systemic treatment of the mice with 10 mg/kg docetaxel increased localization in the tumors. Tumor-to-normal (T/N) ratios were inversely correlated with tumor growth measured over 28 days. These data indicate that (124)I-PGN635 F(ab')2 is a promising new imaging agent for predicting tumor response to therapy.
    PLoS ONE 12/2013; 8(12):e84864. DOI:10.1371/journal.pone.0084864 · 3.23 Impact Factor
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    • "Previous studies have shown that the fluorescent PS-targeting probe, PSS-794, can be used to optically image apoptotic/necrotic tissues often found inside tumors [22]. Here, it is demonstrated for the first time that PSS-794 also allows imaging of 4T1 tumor allografts without an actual infiltration of the probe into the tumor mass. "
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    ABSTRACT: Tumor targeting is of high clinical and biological relevance, and major efforts have been made to develop molecular imaging technologies for visualization of the disease markers in tissue. Of particular interest is apoptosis which has a profound role within tumor development and has significant effect on cancer malignancy. Herein, we report on targeting of phosphatidylserine-exposing cells within live tumor allograft models using a synthetic near infrared zinc(II)-dipicolylamine probe. Visualization of the probe biodistribution is performed with whole body multispectral optoacoustic tomography (MSOT) system and subsequently compared to results attained by planar and tomographic fluorescence imaging systems. Compared to whole body optical visualization methods, MSOT attains remarkably better imaging capacity by delivering high-resolution scans of both disease morphology and molecular function in real time. Enhanced resolution of MSOT clearly showed that the probe mainly localizes in the vessels surrounding the tumor, suggesting that its tumor selectivity is gained by targeting the phosphatidylserine exposed on the surface of tumor vessels. The current study demonstrates the high potential of MSOT to broadly impact the fields of tumor diagnostics and preclinical drug development.
    EJNMMI Research 04/2012; 2(1):14. DOI:10.1186/2191-219X-2-14
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    Journal of Physical Chemistry Letters 09/2010; 1(17):2524-2529. DOI:10.1021/jz100817z · 7.46 Impact Factor
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