Intraoperative, intravascular and endoscopic tumor and lesion detection, biopsy and therapy

Abstract

Methods are provided for close-range intraoperative, endoscopic and intravascular detection and treatment of lesions, including tumors and non-malignant lesions. The methods use antibody fragments or subfragments labeled with isotopic and non-isotopic agents. Also provided are methods for detection and treatment of lesions with photodynamic agents and methods of treating lesions with a protein conjugated to an agent capable of being activated to emit Auger electron or other ionizing radiation. Compositions and kits useful in the above methods are also provided.

Description

[0001] This application is a continuation-in-part of U.S. Ser. No. 08 / 293,313, filed on Aug. 22, 1994, now U.S. Pat. No. 5,716,595, which is a continuation of U.S. Ser. No. 07 / 879,857, filed on May 6, 1992, now abandoned. These cited applications are incorporated herein in their entirety by reference.[0002] 1. Field of the Invention[0003] The present invention relates to improved methods for detecting and treating tumors and lesions and obtaining biopsy material in the course of intraoperative, laparoscopic, intravascular, and endoscopic examination using a small detection instrument or monitor. In preferred embodiments, the methods utilize a labeled divalent single chain antibody fragment or subfragment with a molecular weight of 85,000 daltons or less that specifically binds to an antigen produced by or associated with the tumors or lesions. Alternatively, bispecific F(ab).sub.2 and F(ab').sub.2 fragments can also be used for pre-targeting according to the present invention, if no...

AI Technical Summary

Benefits of technology

[0021] A principal object of the present invention is to provide methods for close-range intraoperative, laparoscopic intravascular, and endoscopic detection of tumors whereby discrimination between tumor and non-tumor tissue is enhanced so that smaller tumors can be detected and appropriate margins can be determined more accurately to permit resection, irradiation, biopsy and / or tumor removal during the procedure and within hours of an injection of labeled protein, whereby surgical, intravascular, laparoscopic, endoscopic evaluation is not delayed.

[0040] In another aspect, the invention provides an injectable composition, which comprises a substantially monospecific antibody having a specific immunoreactivity of at least 70% to a marker produced by or associated with a lesion and a cross-reactivity to non-lesion-associated antigens of less than 25%; the protein being labeled with a labeling agent capable of detection with a detection device, said labeling being effected to an extent sufficient to reduce the specific immunoreactivity of the antibody by from 5 to 33%; indifferent protein from the same or different species as that used to prepare said specific antibody, said indifferent protein being labeled with a labeling agent capable of independent detection by the detection device; and a pharmaceutically acceptable injection vehicle wherein at least one of the labeling agents is a photoactive dye.

Problems solved by technology

Non-invasive RAID is inherently limited by the distance between the radiation detector and the tumor.

In the case of small, deep-seated metastatic tumors, this becomes the limiting factor in their detection.

Nevertheless, elevated background radiation levels can interfere with and vitiate the advantage of short measuring distances in this technique.

In addition, non-specific immunoglobulin uptake by tumor tissue can complicate diagnosis.

However, these earlier studies did not include use of endoscopic imaging and / or therapy or biopsy applications, especially with the use of antibody fragments or subfragments.

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