Intraoperative and endoscopic tumor detection and therapy

Claim 1

In a method for short-range intraoperative detection of a tumor, wherein a surgical patient is injected parenterally with a radiolabeled primary antibody which specifically binds a marker produced by or associated with a tumor, the surgically exposed interior of a body cavity of said patient is scanned at close range with a radiation detection probe, and the sites of accretion of said labeled antibody are located by detecting elevated levels of radiation at said sites with said probe, the improvement comprising compensating for or reducing non-target background radiation by injecting said patient parenterally, either concurrently or sequentially, with: (a) a contrast or subtraction agent radiolabeled with a radioisotope emitting at an energy which is separately detectable from the primary antibody label using a radiation detection probe; radiation detected from emission of the contrast or subtraction agent being used to better define the tumor, wherein: (i) said contrast or subtraction agent comprises an organ, blood pool or interstitial fluid non-tumor-specific contrast agent, and the resultant diffuse distribution of the contrast agent is used to define the organ, blood pool or interstitial region, whereby foci of labeled primary antibody activity are enhanced and better discriminated against a background of reduced diffuse contrast agent label activity; or (ii) said contrast or subtraction agent is a dual isotope correction agent comprising irrelevant immunoglobulin from the same or different species as that used to prepare the primary antibody, the irrelevant immunoglobulin being so labeled that the kinetics and distribution of the radiolabeled primary antibody and irrelevant immunoglobulin in the patient are substantially the same during the time period required for scanning; and wherein the ratio of primary antibody label activity to irrelevant immunoglobulin label activity at a selected site is compared to said ratio at a known non-tumor site, whereby an elevated level of primary antibody label accretion due to antigen-antibody complex formation at said selected site can be discriminated; (b) unlabeled second antibody which specifically binds the primary antibody or the labeling moiety thereof, the second antibody being injected at a time after the injection of the primary antibody sufficient to permit specific uptake of the primary antibody by a tumor in the body cavity, and in an amount sufficent to reduce the circulating level of the primary antibody label by at least about 10-85%, or to increase the localization ratio of the labeled primary antibody by at least about 20%, within about 2-72 hours following injection of the second antibody, whereby background levels of nonspecifically distributed primary antibody and/or label are reduced in the body cavity, and the sites of accretion of labeled primary antibody as well as the level of specific uptake thereof are more effectively discriminated.

Claim 8

A method for short-range endoscopic tumor detection, comprising injecting an endoscopy patient parenterally with a radiolabeled primary antibody which specifically binds a marker produced by or associated with a tumor, scanning the endoscopically accessed interior of a body cavity of said patient at close range with a radiation detection probe, and locating the sites of accretion of said labeled antibody by detecting elevated levels of radiation at said sites with said probe.

Claim 9

A method for short-range endoscopic tumor detection, comprising injecting an endoscopy patient parenterally with a radiolabeled primary antibody which specifically binds a marker produced by or associated with a tumor, scanning the endoscopically accessed interior of a body cavity of said patient at close range with a radiation detection probe, and locating the sites of accretion of said labeled antibody by detecting elevated levels of radiation at said sites with said probe.