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

Abstract

Nude mice bearing CX-1 colon tumors were injected with 50 microCi 125I-labeled monoclonal antibody (MAb) B72.3. Radioactivity in tumors was studied with the gamma detecting probe (GDP) on days 1, 3, 7, and 10 after MAb injection. On each day, two mice were sacrificed and sections were examined with autoradiography (ARG), immunoperoxidase methods (IMP), and routine stains. Mean probe counts showed increasing tumor to background ratios and ARG demonstrated a progressive increase in radionuclide in the tumors. The distribution of 125I was primarily around the vascular spaces on day 1, but by day 3 and progressively it appeared in tumor gland lumina and necrotic areas. A regional correlation was shown between radionuclide in vascular spaces and its sequestration in tumor elements.

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

“…The causes of heterogeneity of intratumour distribution of antibody have been addressed by Cobb, 1989 andJain andBaxter, 1988 and the consequences of nonuniformity of antibody binding on tumour dose in radioimmunotherapy are discussed by Humm and Cobb, 1990. Most autoradiographic studies of the distribution of antibody at the microscopic level have been confined to human tumour xenograft model systems in nude mice (Pedley et al, 1990;Sampsel et al, 1990). In patients, tumour and normal tissues from resected specimens collected following radioimmunoguided surgery with '25I-labelled antibody (Blair et al, 1990), allows the microdistribution of antibody to be investigated.…”

Population Pharmacokinetics of Humanized Monoclonal Antibody HuCC49ΔCH2 and Murine Antibody CC49 in Colorectal Cancer Patients

“…Three generations of anti‐TAG‐72 MAbs (murine B72.3, murine CC49, and humanized CC49ΔCH2) have been evaluated in xenograft models and in RIGS in humans. RIGS with B72.3 localized 77% to 89% of primary colorectal tumors in 61 patients 3,7,8 and 78% of metastatic lesions in lymph nodes and livers in 78 patients 9–22 . In comparison, CC49 detected 86% of primary colorectal cancers in 57 patients and 97% of recurrent tumors in 30 patients 2,23–27 .…”

“…RIGS with B72.3 localized 77% to 89% of primary colorectal tumors in 61 patients 3,7,8 and 78% of metastatic lesions in lymph nodes and livers in 78 patients. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] In comparison, CC49 detected 86% of primary colorectal cancers in 57 patients and 97% of recurrent tumors in 30 patients. 2,[23][24][25][26][27] In addition, RIGS with anti-TAG-72 antibodies not only detects visible gross tumors for precise surgery but also detects clinically occult tumors, which are normally undetectable by traditional surgical exploration.…”