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Internal image antibodies for optical imaging and therapy

an optical imaging and antibody technology, applied in the field of bioconjugates containing internal image antibodies, can solve the problems of lack of stability of many biological receptors, inability to perform ultrasonic/sonic/infrasonic diagnostics, etc., and achieve the effect of sufficient power and fluency

Inactive Publication Date: 2009-01-15
RAGAJOPALAN RAGHAVEN +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This observation, however, is not general and it is not possible at this time to predict a priori the binding properties of small molecule bioconjugates with a high degree of confidence.
This is often not possible for various reasons, including the lack of stability of many biological receptors.
Thus, most receptor targeting with anti-receptor antibodies have been elusive.

Method used

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  • Internal image antibodies for optical imaging and therapy
  • Internal image antibodies for optical imaging and therapy
  • Internal image antibodies for optical imaging and therapy

Examples

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example 1

Preparation of Digoxin Internal Image Antibody Fab′ Fragments and Conjugation to an Optical Diagnostic Agent

[0052](a) Fusion of Mouse Myeloma Cells with the Spleen Cells of AJ Mice Immunized with Balb-C Mouse Anti-Digoxin Antibody.

[0053]Monoclonal antibodies were produced using standard hybridoma technology, as is known to one of ordinary skill in the art. Briefly, two AJ mice were immunized with murine (Balb-C) monoclonal anti-digoxin antibody (Medex Laboratories). A booster injection was given three weeks after the primary immunization and the spleens were removed after three days. Mouse myeloma and spleen cells were washed three times with Dulbecco's Modified Eagle Medium (DME) and suspended in DME (10 ml). A 5 mL portion of each of these cell suspensions was mixed and centrifuged. The supernatant was discarded and the pellet was treated with 1 mL polyethylene glycol (added over a 45 second period), 3 mL DME (added over a 30 second period), and an additional 9 mL of DME was added...

example 2

Preparation of Digoxin Internal Image Antibody Fab′ Fragments and Conjugation to a Phototherapeutic Agent

[0064]The Fab′ fragments (2) obtained in Example 1, step (c) are used for conjugation to a phototherapeutic agent. The conjugation procedure is carried out in a manner similar to the one published previously for human serum albumin (Achilefu et al., Investigative Radiology, 2000, 35, 479-485), which is expressly incorporated by reference herein in its entirety.

[0065]With reference to FIG. 2, a mixture of the Fab′ fragment (2) and about 20 fold molar excess of the photosensitizer active ester (4), is incubated in PBS for four hours. The phototherapeutic conjugate (5) is purified by Sephadex G-25 size exclusion chromatography using PBS as the eluant, and is subsequently lyophilized.

example 3

Preparation of Whole Digoxin Internal Image Antibodies and Conjugation to an Optical Diagnostic Agent

[0066]Whole digoxin internal image antibodies obtained in Example 1, steps (a) and (b) were used for conjugation to a photodiagnostic agent. The conjugation procedure was carried out in a manner similar to the one published previously for human serum albumin (Pandurangi et al., Journal of Organic Chemistry, 1998, 63, 9019-9030).

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Abstract

Methods using internal image antibodies for photodiagnosis and / or phototherapy. The internal image antibodies are conjugated with a photoactive molecule such as a dye or photosensitizer, to target specific regions, such as biological receptors. The photoactive molecules are then activated for diagnosis or therapy. Advantageously, the internal image antibody is specific for a biological receptor, but does not require isolation of the receptor to prepare the antibody, and provides the desired specificity and selectivity for targeted diagnosis or therapy.

Description

RELATED APPLICATION[0001]This application is a Division of and claims priority to co-pending allowed U.S. patent application Ser. No. 10 / 761,634 filed Jan. 21, 2004, which claims priority to abandoned U.S. patent application Ser. No. 09 / 919,243 filed Jul. 31, 2001, each expressly incorporated by reference herein in its entirety.FIELD OF THE INVENTION[0002]The invention relates generally to diagnosis and therapy using photoactive compounds. More particularly, the invention relates to bioconjugates comprising internal image antibodies or their fragments attached to photoactive molecules.BACKGROUND OF THE INVENTION[0003]The use of visible, near-infrared (NIR), and low-energy ultraviolet light in clinical practice is growing rapidly. Compounds absorbing or emitting in the visible, NIR, or long wavelength (UV-A, >350 nm) region of the electromagnetic spectrum are potentially useful for diagnostic techniques such as tomographic or planar imaging, endoscopic examination, optoacoustic im...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K49/00A61K39/395A61K41/00A61P7/02A61P9/10A61P35/00A61P43/00C07K16/28C07K16/42C12P21/08
CPCA61K49/0032A61K49/0058A61K41/0071C07K16/4208A61K2039/505A61P35/00A61P43/00A61P7/02A61P9/10
Inventor RAGAJOPALAN, RAGHAVENBUGAJ, JOSEPH E.ACHILEFU, SAMUEL I.DORSHOW, RICHARD B.
Owner RAGAJOPALAN RAGHAVEN
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