Dr. Iven Jose Profile

Dr. Iven Jose

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Publications (3)

Proceedings Article | 17 February 2011 Paper

Early detection of breast cancer: a molecular optical imaging approach using novel estrogen conjugate fluorescent dye

Shubhadeep Bhattacharjee, Iven Jose

Proceedings Volume 7896, 78961F (2011) https://doi.org/10.1117/12.873387

KEYWORDS: Luminescence, Breast, Breast cancer, 3D modeling, Tumors, Optical imaging, In vitro testing, Receptors, Absorption, Tissues

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Proceedings Article | 26 February 2010 Paper

Estrogen receptor-targeted optical imaging of breast cancer cells with near-infrared fluorescent dye

Iven Jose, Kodand Deodhar, Shuba Chiplunkar, Meena Patkar

Proceedings Volume 7568, 75680J (2010) https://doi.org/10.1117/12.843158

KEYWORDS: Tumors, Luminescence, Receptors, Breast cancer, Optical imaging, Tissues, Molecules, Near infrared, Sodium, Oncology

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Molecular imaging provides the in vivo characterization of cellular molecular events involved in normal and pathologic processes. With the advent of optical molecular imaging, specific molecules, proteins and genes may be tagged with a luminescent reporter and visualized in small animals. This powerful new tool has pushed in vivo optical imaging to the forefront as it allows for direct determination of drug bio-distribution and uptake kinetics as well as an indicator of biochemical activity and drug efficacy. Although optical imaging encompasses diverse techniques and makes use of various wavelengths of light, a great deal of excitement in molecular research lies in the use of tomographic and fluorescence techniques to image living tissues with near-infrared (NIR) light. Nonionizing, noninvasive near-infrared optical imaging has great potential to become promising alternative for breast cancer detection. Fluorescence spectroscopy studies of human tissue suggest that a variety of lesions show distinct fluorescence spectra compared to those of normal tissue. It has also been shown that exogenous dyes exhibit selective uptake in neoplastic lesions and may offer the best contrast for optical imaging. Use of exogenous agents would provide fluorescent markers, which could serve to detect embedded tumors in the breast. In particular, the ability to monitor the fluorescent yield and lifetime may also enable biochemical specificity if the fluorophore is sensitive to a specific metabolite, such as oxygen. As a first step, we have synthesized and characterized one such NIR fluorescent dye conjugate, which could potentially be used to detect estrogen receptors (ER)[2] . The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of indocyanine green (ICG) cyanine dye, bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5- carboxylic acid, sodium salt. The ester formed was found to have an extra binding ability with the receptor cites as compared to ICG, which was established by the partition coefficient studies. The replacement of the sodium ion in the ester by a larger glucosammonium ion was found to enhance the hydrophilicity and reduce the toxic effect on the cell lines. The excitation and emission peaks for the conjugate were recorded in the NIR region as 750nm and 788nm respectively. The ester was found nontoxic on adenocarcinoma breast cancer cell lines MCF-7/MDA-MB-231. Specific binding and endocytosis of the estrogen-labeled conjugate was studied on the MCF-7 (ER positive) and MDA-MB-231 (ER negative). Conjugate staining of MCF-7 cells showed ~ 4-fold increase in signal intensity compared to MDA-MB- 231. Further, estrogen molecules were found to be specifically localized to the nuclear region of MCF-7 cells, whereas MDA-MB-231 showed plasma membrane staining. This technique offers the potential of noninvasive detection of hormone receptor status in breast cancer cells and would help in decreasing the load of unnecessary biopsies. Here, we have reported the progress made in the development of a novel NIR external contrast agent and the work is in progress to use this conjugate for the molecular based, diagnostic imaging of breast cancer.

Proceedings Article | 28 April 2005 Paper

Non-invasive imaging of breast cancer: synthesis and study of novel near-infrared fluorescent estrogen conjugate

Iven Jose, Gargi Vishnoi, Kodand Deodhar, Uday Desai

Proceedings Volume 5693, (2005) https://doi.org/10.1117/12.589571

KEYWORDS: Breast cancer, Near infrared, Receptors, Quantum efficiency, Luminescence, Sodium, Absorption, Tissue optics, Ions, Mammography

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The use of near-infrared (NIR) spectroscopy to interrogate deeper tissue volume has shown enormous potential for molecular-based non-invasive imaging when coupled with appropriate excitable dyes. As most of the breast cancers are hormone dependent hence determination of the hormonal receptor status gains paramount importance when deciding the treatment regime for the patient. Since proliferations of the breast cancer cells are often driven by estrogen, we focus on to developing a technique to detect estrogen receptor status. As a first step, the objective of this work was to synthesize and characterize one such novel NIR fluorescent (NIRF) conjugate, which could potentially be used to detect estrogen receptors. The conjugate was synthesized by ester formation between 17-b estradiol and a cyanine dye namely: bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. The cyanine dye is a hydrophilic derivative of indocyanine green (ICG). The ester formed was found to have an extra binding ability with the receptor cites as compared to ICG, which was established by the partition coefficient studies. This cyanine dye has a partition coefficient less than 0.005 as compared to that of ICG (>200)[1]. In addition the ester showed enhanced fluorescent quantum yield than ICG. The replacement of the sodium ion in the ester by a larger glucosammonium ion was found to enhance the hydrophilicity and reduce the toxic effect on the cell lines. The excitation and emission peaks for the conjugate were recorded in the NIR region as 750nm and 788nm respectively. The ester developed was tested on the breast cancer cell lines MCF-7 and found non-toxic. The tagging characteristics were pivotal determinants underlying the ability of the fluorescent conjugate in binding the estrogen receptor of the breast cancer cells. This technique offers the potential of non-invasive detection of hormone receptor status in vivo and may help in decreasing the load of unnecessary biopsies. Here, we have reported the progress made in the development of a novel NIR external contrast agent and the work is in progress to use this conjugate for the molecular-based, diagnostic imaging of breast cancer.

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