Radioiodinated peanut lectin: A potential radiopharmaceutical for immunodetection of carcinoma expressing the T antigen

Abstract

The Thomsen-Friedenreich (T) antigen, beta-D-Gal-(1 leads to 3)-alpha-D-GalNAc, is exposed in reactive form on many human adenocarcinomata, but not on corresponding benign tissues. Peanut lectin (PNA) has a strong binding affinity for the T antigen and reportedly binds preferentially to certain malignant tissues. We investigated the potential of radiolabelled PNA as a tumour localising agent in an animal model system using a mouse lymphoma (RI) shown to bind fluorescein-labelled PNA in vitro. The radioiodinated lectin showed good tumour localization and rapid blood clearance. Clear images of tumours were obtained, in serial scintigraphic imaging, by 24 and 48 h. No blood background subtraction was necessary. Biodistribution studies revealed tumour to blood ratios in mice were 6:1 (at 24 h) and 17:1 (at 48 h), and tumour to muscle ratios were 34:1 (at 24 h) and 40:1 (at 48 h). Rapid in vivo breakdown of 125I-PNA led to some localization of free iodide in the kidneys, stomach, thyroid and salivary glands.

Triple Role of T and Tn Antigens in Cancer: as Universal, Clonal Carcinoma Markers, in Cancer Cell Adhesion, and as Autoimmunogens

“…The potential for manipulating immune responses to metastases with labeled anti-T reagents, including monoclonal anti-T and anti-Tn antibodies, is currently under inves tigation [101;Metcalfe and Springer,unpub lished]. Using the T-anti-T system in probing the dynamic interaction of the patient with his CA promises to deepen our comprehen sion of the pathogenesis of this dyscrasia.…”

“…There are indications that this may become possible. A promising effort that resulted in tumor localization has been made with radioiodinated lectin from Arachis hypogaea in tumor-bearing mice [101]. The Arachis lectin has a high affinity for the T-specific hapten Gal(31-»3GalNAc, even though it is of lesser specificity than human anti-T [cf.…”

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.…”