In vivo localization of radioiodinated peanut lectin in a murine TA3/Ha mammary carcinoma model

Abstract

Peanut lectin (PNA) binds avidly to oligosaccharides containing the terminal sequence beta-D-Gal(1----3)alpha-D-GAlNAc. This disaccharide is the immunodeterminant group of the Thomsen-Friedenreich (T) antigen which is present in an exposed form on a number of human and animal adenocarcinomas and can be identified in tumor tissue sections by histochemical PNA staining techniques. We have studied the in vivo uptake of radioiodinated PNA in a murine TA3/Ha mammary adenocarcinoma model to evaluate the potential applications of radiolabeled PNA for the immunodetection of T antigen expressing carcinoma. We have found that PNA has a high in vitro binding affinity for the TA3/Ha tumor cells as well as for epiglycanin, a glycoprotein fraction shed by the TA3/Ha cells. Tissue biodistribution studies after IV 125I-PNA injection into TA3/Ha tumor-bearing mice indicated tumor:blood ratios of 7:1 and 55:1 at 24 and 48 h with corresponding tumor:muscle ratios of 33:1 and 77:1. The high tumor uptake and rapid blood clearance allowed clear scintigraphic delineation of tumor by 24 and 48 h without the necessity for background subtraction techniques. Rapid in vivo deiodination of 125I-PNA also contributed to localization of radioactivity in the stomach, salivary glands, thyroid, and kidney.

Cancer vaccines and carbohydrate epitopes

“…In addition TF-Ag can be modulated by sulfation [97,98]. The closely related Galβ1–3GalNAc β is present in glycolipids of the spleen white and red pulp [99], kidney tubules [100,101], regenerating respiratory epithelial cells [100], and NK cells [102,103]. Therefore, the vaccine response must be specific in order for this antigen to be targeted.…”

Tumor immunolocalization using 124I-iodine-labeled JAA-F11 antibody to Thomsen–Friedenreich alpha-linked antigen

“…The 170H.82 antibody recognizes both the alpha-and beta-linked derivatives (Galβ1-3GalN Acα and Galβ1-3GalNAcβ) of TF-Ag and, therefore, could potentially interact with carbohydrate structures expressed on normal tissues such as asialo-GM1 (a natural killer cell marker), whereas JAA-F11 does not (Longenecker et al, 1987). No testing of the 170H.82 antibody in mice was reported, but the Longenecker group did perform in vivo tumor localization experiments with 2 other similar reagents which also bind both the TF-Ag-α and β derivatives: radiolabeled peanut lectin (PNA) (Shysh et al, 1985;Abdi et al, 1986) and radiolabeled mAb 155H.7 (Turner et al, 1988) which they reported to be similar to mAb 170H.82 (Longenecker et al, 1987). The PNA radiolocalized to the kidney both in mice (72 hours, kidney:tumor ratio of 1.3) (Shysh et al, 1985) and in humans (17 patients, only 1 in which PNA localized to a tumor) (Abdi et al, 1986).…”

The application of lectins to the characterization and isolation of mammalian cell populations

“…A particularly interesting third application of radiolabelled lectins is in the scintigraphic localization of tumors in vivo [98][99][100]. Like studies employing monoclonal antibodies, the goal of this undertaking is to precisely detect the location of tumor loci (Fig.…”

“…The use of iodinated PNA has been reasonably successful in attempts to scintigraphically localize murine mammary carcinomas [99,100], but less so in imaging human breast, colon, and lung carcinomas [98]. Hopefully, this novel line of investigation will continue with additional lectins that are better suited to the imaging of human tumors.…”

“…Examples of these applications are numerous: lectins have been used to examine membrane fluidity [73], receptor distance on membranes [84], the process of endocytosis [94,129], and cell attachment mechanisms [130], and to select or isolate cells desired for functional differences, such as differing metastatic ability [131][132][133] or transplantability in bone marrow cell populations [105,106]. Further uses of lectins are evident when purifying or characterizing various components of cells, including cell surface glycoproteins [98][99][100] and glycolipids [101]. The use of lectins to monitor the binding of laminin to cell surface receptors [86] is an example of the way lectins may be used to monitor the addition of extrinsic moieties to cells.…”