Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin

Abstract

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin Was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection.[99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.

Molecular Imaging of the Cardiac Extracellular Matrix

“…Antitenascin antibodies by direct 70 and pretargeting 71 approaches have been used for clinical targeting of tenascin C to localize gliomas. 111 In-labeled antitenascin C monoclonal antibody Fab′ fragment has also been used to detect experimental Tc-lisinopril micro-SPECT/CT images in control rats (A1), angiotensin-converting enzyme (ACE-1)-overexpressing transgenic rats (A2), and ACE-1-overexpressing transgenic rats after cold lisinopril pretreatment (A3).…”

Tumor-Targeting Properties of Novel Antibodies Specific to the Large Isoform of Tenascin-C

“…Furthermore, efficient tumor targeting by anti-tenascin antibodies has been shown clinically using an avidin/biotin-based pretargeting approach (37) or, more recently, with monoclonal antibodies specific for the small isoform of tenascin-C (38,39). However, all these antibodies are of murine origin and may therefore not be suitable for repeated administration to patients and for the development of biopharmaceuticals.…”

Pretargeted immunoscintigraphy in patients with medullary thyroid carcinoma

“…However, after injection of directly labelled MAb, image interpretation is sometimes difficult because of non-specific bone marrow, vascular and liver activity (Peltier et al, 1993). In CEApositive tumours, gliomas and lung cancers (Paganelli et al, 1994a;Dosio et al, 1994), and more recently in neuroendocrine tumours using an anti-CgA MAb (Colombo et al, 1993), the avidin-biotin pretargeting method provides good results and offers several advantages over the administration of directly labelled MAbs. A fast label clearance and removal of circulating antibodies, with low background radioactivity levels, and the preservation of MAb immunoreactivity (Paganelli et al, 1991) were demonstrated.…”