PRE-TARGETED IMMUNODETECTION IN GLIOMA PATIENTS - TUMOR-LOCALIZATION AND SINGLE-PHOTON EMISSION TOMOGRAPHY IMAGING OF [TC-99M]PNAO-BIOTIN

The imaging of cerebral gliomas with radiolabelled monoclonal antibodi es (MoAbs) has been previously reported. However, previous studies hav e been hampered by the drawback of a low tumour to non-tumour ratio. I n order to overcome this problem we have developed a three-step pre-ta rgeting method using the avidin-biotin system. The rationale of this t echnique consists in vivo labelling of biotinylated MoAbs targeted ont o tumour deposits, when most of the unbound antibodies have been clear ed from the bloodstream as avidin-bound complexes. The anti-tenascin M oAb 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. follow ed 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-in jection. [Tc-99m]PnAO-biotin had a fast blood clearance and was primar ily excreted through the biliary system. A dedicated single-photon emi ssion tomography system was used to acquire brain tomographic images 1 -2 h after the administration of [Tc-99m]PnAO-biotin. Tumours were det ected 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 [Tc-99m]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis a nd follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.