Simultaneous use of lysosomal inhibitors improves uptake of labeled antibody in human high grade glioma cells in vitro

Journal Article · Sun May 01 04:00:00 EDT 1994 · Journal of Nuclear Medicine

OSTI ID:198091

Emrich, J G; Class, R; Brady, L W ^[1]

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1. Hahnemann Univ., Phildelphia, PA (United States); and others

Malignant glioma cells, known to overexpress the epidermal growth factor receptor (EGF-r), have been targeted both in vitro and in vivo by the murine monoclonal antibody MAb-425 ({alpha}-EGF-r). MAb-425, radiolabeled with Iodine-125 (I-125), demonstrates substantial cell kill when the energetic cascade of Auger electrons is deposited close to the DNA. Due to the short range of the electron cascade, nearby normal brain cells with negligible EGF-r are not harmed by the radiation`s energy, making it a good choice for radioimmunotherapy. Human high grade glioma cell lines were evaluated in vitro for intracellular as well as nuclear accumulation of I-125 MAb-425. Binding and internalization studies revealed that this MAb is degraded following receptor-mediated endocytosis. In an attempt to inhibit lysosomal degradation and subsequently increase tumor cell uptake, lysomotropic agents such as chloroquine and monensin were employed. Glioma cell lines with varying EGF-r densities were incubated with and without these inhibitors (2-48 hr) and analyzed for cellular and nuclear accumulation. At a 50 {mu}M concentration, chloroquine significantly increased the intracellular concentration (3-fold) and nuclear accumulation (3-10-fold) compared to untreated cells. Monensin, under comparable conditions, showed modestly enhanced nuclear uptake (2-fold). Our data suggest that the use of lysosomal inhibitors in combination with I-125 MAb-425 can enhance intracellular as well as nuclear accumulation in glioma cells, improving radiotoxic effects in vitro. This approach could benefit the ongoing radioimmunotherapy of glioma patients treated with I-125 MAb 425.

• OSTI ID: 198091
• Report Number(s): CONF-940605--
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN 0161-5505; ISSN JNMEAQ
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BRAIN
CELL KILLING
GLIOMAS
IODINE 125
MONOCLONAL ANTIBODIES
PATIENTS
RADIOIMMUNOTHERAPY
TUMOR CELLS
UPTAKE