Intraoperative radioimmunolocalization of colorectal carcinoma with a hand‐held gamma probe and MAb B72.3: Comparison of in vivo gamma probe counts with in vitro MAb radiolocalization

Abstract

A new intraoperative approach to tumor localization using radiolabelled monoclonal antibody (MAb) B72.3 involves the use of a hand-held gamma-detecting probe (GDP) by the surgeon and, subsequently, the pathologist. We report here the use of 125I-labelled MAb B72.3 IgG and a GDP to localize primary and metastatic colorectal cancer in 31 patients. The patients were administered radiolabelled MAb i.v., and all underwent surgical exploration 5 to 35 days post-injection. In vivo localization of the MAb was evaluated using a GDP, with tumor and normal tissue counts being obtained. In each case, the subsequent tumor and normal tissue that were resected were analyzed in vitro for MAb localization; this was evaluated by calculating the radiolocalization index, i.e., the ratio of the injected dose per gram localized to tumor versus that of normal tissue. When the GDP was used intraoperatively, MAb B72.3 localized tumors in 68% (21/31) of the patients; the arbitrary criterion of tumor-to-normal tissue ratios higher than or equal to 2.0:1 in vivo being taken as positive. Resected tumor radiolocalization indices ranged from 0.5 to 543, and 71% (22/31) of the patients studied had tumors with radiolocalization indices higher than or equal to 3. Of 50 carcinoma biopsies, 34 that were probe-positive were antigen-positive when B72.3 was used in immunoperoxidase assays, while 4 carcinoma biopsies that were probe-negative were also antigen-negative. Twelve of 50 biopsies were probe-negative and antigen-positive, but many of these lesions only contained a few antigen-positive cells; none of the 50 was probe-positive and antigen-negative. Tumors of all histologic grades localized injected MAb and, in general, higher in vivo probe ratios and radiolocalization indices were obtained from patients who underwent surgery 20 to 35 days following injection of the MAb. MAb B72.3 localized tumor in all sites to which colon carcinoma commonly metastasizes, including mesenteric and peri-aortic lymph nodes, liver, lung, and peri-rectal soft tissue. There was a strong statistical correlation (p = 0.001) between detecting MAb B72.3 localization to tumors using the GDP intraoperatively and subsequent in vitro analysis of cpm/g for tumor versus normal tissues. These studies thus further validate the use of 125I-labelled MAb B72.3 IgG and of a hand-held gamma probe for the intraoperative detection of carcinomatous lesions.

Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma – implications for radioimmunotherapy

“…The preoperative administration of radiolabelled antibody for use with RIGS (Blair et al, 1990;Tuttle et al, 1988) provides an opportunity to obtain tissue samples from patients receiving antibody which are suitable for studying the relevant parameters. Autoradiography, combined with immunohistochemical demonstration of CEA and vascular endothelium, shows the relationship of localised antibody to the target antigen and tumour vasculature.…”

Gamma‐detecting probe and autoradiographic studies of radiolabeled antibody B72.3 in CX‐1 colon xenografts

“…Total counts decline in neoplasms with time, but the increasing background-to-tumor ratios make for more efficient localization by probe or other means, like scintigraphy [5], or well counting to provide radiolocalization indices [6]. Delays between I2'I MAb injection and clinical optimal detection of cancers intraoperatively with radioimmunoguided surgery have been approximately 21 days [l].…”

Animal Models for Radiolabeled Monoclonal Antibodies in Cancer Research

“…The antibody will be found in most organs, and will persist for a shorter or longer time period in blood and other body fluids. Consequently, the target/non-target ratio is often unfavorable for diagnostic imaging (70), and even more so for radioimmunotherapy (71). Alternative routes of injection, such as intraarterial (72) or intracavitary approaches (51,(73)(74)(75), or direct injection into the tumor (50), may improve the specific tumor uptake.…”