Pre-injection of unlabeled monoclonal antibody improves the uptake of labeled antibody in glioma patients in vivo

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

OSTI ID:197961

Bender, H ^[1]; Emrich, J G; Brady, L W ^[2]

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1. Univ. of Bonn (Germany)
2. Hahnemann Univ., Phildelphia, PA (United States); and others

As part of an ongoing clinical phase II trial, high grade glioma patients received 3 i.v. injections of 50 mCi I-125 labeled monoclonal antibody 425 following conventional therapy (surgery and external beam radiation). MAb 425 binds specifically to the human epidermal-growth factor receptor, that is overexpressed in high grade gliomas but absent in normal brain tissue. We have previously reported that biodistribution of I-125 labeled MAb 425 can be monitored with a hand-held Iodide-crystal detector system in these patients in vivo. We were able to demonstrate that repeated injections resulted in a reproducible activity distribution pattern in the various organs of the 1st, 2nd and 3rd injection. Additionally, we observed that most of the injected MAb is captured by the this study was to investigate the unlabeled relevant MAb on the biodistribution of I-125 labeled MAb 425. Patients received 3 injections of 50 mCi I-125 labeled MAb 425 (3.2 mg) in a weekly interval. Prior to the 2nd treatment, patients were pre-injected with 10 mg (N=3), 40 mg (N=4) or 60 mg (N=2) unlabeled MAb 425. The results were compared to the 1st and 3rd. injection. Our data show, that pre-injection of increasing doses (0-60 mg) of unlabeled MAb resulted in a dose-dependent increase of radioactivity maximum uptake and area-under-the-curve (AUC) in the blood-pool (AUC 1st. vs. 2nd inj..: 2.2x10{sup 6} vs 9.9xl0{sup 6} cpm-hrs) and tumor tissue (9.6x10{sup 5} vs. 2.5x10{sup 6} cpm-hrs), but also in normal brain (5.9x10{sup 5} vs. 1.8x10{sup 6} cpm-hrs). At the same time, maximum accumulation of radioactivity in the liver was significantly reduced. Additionally, pre-injection reduced dehalogenation and prolonged the immunoreactivity TCA-precipitation and EGF-R suggest, that pre-injection of labeled MAb in tumor tissue mainly by reducing or retarding specific and unspecific liver uptake and by reducing dehalogenation and thus preserving immunoreactivity.

• OSTI ID: 197961
• 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
BLOOD
BRAIN
GLIOMAS
IN VIVO
IODINE 125
LABELLED COMPOUNDS
LIVER
MONOCLONAL ANTIBODIES
PATIENTS
RADIOTHERAPY
UPTAKE