Radioimmunolocalisation of human brain tumours: Biodistribution of radiolabelled monoclonal antibody UJ13A

Abstract

Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h. Dynamic and static scintigrams indicated some early sequestration of radiolabelled antibody by the liver. Tumours were surgically resected in seven patients at various intervals after antibody administration showing tissue to blood ratios increasing with time in all parts of the lesion (viable and necrotic tumour, cyst fluid), and in normal brain. The highest tissue to blood ratio in viable tumour was 5.1 at 16 days after injection. In tissues resected 2-3 days after injection there was relatively greater uptake in the viable tumour compared to necrotic tumour and cyst fluid. In contrast, tissues resected later (6-16 days) showed greater uptake in ischaemic tissue than viable tumour, suggesting diffusion was an important factor influencing tumour uptake. The amount of radioactivity per gram of tumour tissue was less than 0.005% of the injected dose. Future studies are needed using different antibodies, antibody fragments and additional methods of optimising delivery.

Identification of Novel Tumor-Associated Cell Surface Sialoglycoproteins in Human Glioblastoma Tumors Using Quantitative Proteomics

“…Notwithstanding the universal expression of NCAM1 by neuronal cells, three clinical studies have used anti-NCAM1 antibodies in patients. mAb UJ13A was shown to accumulate in gliomas by virtue of disruption of the blood brain barrier locally [71], and another antibody, ERIC-1 armed with radionuclides iodine-131 or yttrium-90, was used in a therapeutic setting in resected glioma cavities with some clinical benefit [72], [73]. Among the lowest abundant proteins (median intensity <10,000), those showing the most enriched expression (Effect size >5.0) in the tumor group compared to the astrocyte group include NTRK2 (also known as TrkB), a tyrosine-protein kinase receptor of the Trk family involved in the development and/or maintenance of the nervous system.…”

Radioimaging of human glioma xenografts with 123I labeled monoclonal antibody G-22 against glioma-associated antigen

“…Previous investigations using subcutaneous or intracranial xenografts of human glioma indicated that the type and specificity of MCA, the kind of radionuclide, the method of administration and the imaging protocol, and the size and nature of tumor were important factors. Several types of MCA against a human glioma surface antigen [10,23,24], a human glioma-mesenchymal extracellular matrix antigen (Tenascin) [25][26][27] or epidermal growth factor receptor [28] were utilized as targets for radioimmunodetection of glioma. We chose G-22 MCA in the present study from the following reasons.…”

“…There were already several reports for clinical application of this new method to the patients with malignant glioma. The results revealed its significance for the diagnosis and localization of tumor and to date no severe medical complication following intravenous, intracarotid, and even intrathecal administration of radiolabeled murine MCAs [23,31,32]. Work is now being directed toward further improvement of specific delivery system through blood-brain-barrier and establishment of early diagnosis of smaller tumors, and also settlement of problem for hypersensitization of the patients due to multiple injection of foreign protein.…”

Tumor antigens in astrocytic gliomas

“…The CD-44 molecule, which is a 90 kDa transmembrane glycoprotein, has recently emerged as a potentially significant marker for gliomas. In vitro studies demonstrating the invasion of cultured glioma cells into a matrigel medium, which was inhibited by both MAbs against CD-44 and antisense mRNA constructs (Merzak Strawn et al, 1994;Nister et al, 1988Nister et al, ,1991Hermanson et al, 1988Papanastasiou et al, 1993Richardson et al, 1986Wikstrand et al, 1991;Fukuda et al, 1986;Fukushi et al, 1986Wikstrand et al, 1993Fukuda et al, 1986;Fukushi et al, 1986Li et al, 1993Merzak et al, 1994;Pilkington et al, 1993Foresta et al, 1991, Owens et al, 1992, Reeves et al, 1994Garcia Palazzo et al, 1993 (see footnote' to text) Molenaar et al, 1991;Edvardsen et al, 1991Lendahl, 1990…”