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.

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.

No abstract

No abstract

Organ-specific lung and liver metastatic variants of the murine TA3/Ha mammary adenocarcinoma cell line were selected by sequential in vivo growth with intervening in vitro cell culture. These variants readily formed specific lung or liver metastatic lesions upon i.v. injection into A/J mice. TA3/Ha cells produce a large cell surface glycoprotein called epiglycanin, which contains a high proportion of Thomsen-Friedenreich (TF) antigenic structures. The presence of non-cryptic TF has been associated with malignancy in humans and animals. We used peanut lectin agglutinin (PNA), which has a preferential affinity for TF antigenic structures, to determine whether these selected metastatic variants retained the TF antigen expression. In vitro, the TA3/Ha metastatic variant lines exhibited strong PNA binding similar to that seen with human RBC after neuraminidase treatment to expose the cryptic TF antigen. In contrast, the non-epiglycanin-producing TA3/St subline did not bind PNA appreciably. Autoradiography of liver sections with TA3/Ha metastatic lesions after 125I-PNA i.v. indicated an avid uptake throughout the viable tumor mass and FITC-PNA staining of these tissue sections readily identified the metastatic tumors under fluorescence microscopy. Tissue biodistribution studies revealed that lung or liver containing the TA3/Ha metastatic variant nodules retained about 7 to 8 times as much of an i.v. dose of radioiodinated PNA as did controls, allowing for clear delineation of tumor-infiltrated lung or liver by gamma scintigraphy. These in vitro and in vivo tests confirm that the selected organ-specific TA3/Ha variants retained the binding characteristics of the parent TA3/Ha line. These observations illustrate the potential utility of radiolabelled PNA for the detection of TF-antigen-expressing tumors and metastases. This murine system with organ-specific TA3/Ha metastatic variants also provides a model for evaluation of various other macromolecular probes for tumor radioimmunodetection of metastatic lesions.