Comparing monoclonal antibodies and small peptidic hormones for local targeting of malignant gliomas.
Monoclonal antibodies, F(ab')2 fragments and peptidic vectors have been clinically tested for systemic and locoregional treatment of malignant gliomas. Since these brain-intrinsic neoplasms are characterized by relentless tumor cell infiltration of normal brain parenchyma, targeting agents require diffusive properties in order to reach invading tumor cell clusters that migrate along vascular clefts and axonal pathways. Tumor uptake was significantly improved by using small peptidic hormone receptors, e.g. modified octreotide, following systemic injections as compared to macromolecules which only led to limited stabilization of the disease. More importantly, biodistribution was found to be superior following direct intratumoral injection by using these small drug-like radioconjugates. Rapid and extensive distribution within 30 minutes was observed in large tumors, even crossing the corpus callosum in bihemispheric lesions following injection of 2-3 ml of the radiopharmakon injected into the center of non-resected tumors. Distribution was far more extensive after direct intratumoral injection as compared to intracavitary injection after surgical debulking. Increased interstitial pressure gradients and the much larger and chaotic structure of the interstitial space of a tumor compared to the extremely tight architecture of normal brain tissue might explain this unexpected biodistribution pattern. Peptidic hormone vectors might become useful agents to deliver radiopharmaceuticals into human invasive gliomas.
Merlo
A
A
Neurosurgery, Department of Surgery, University Hospitals, Basel, Switzerland. amerlo@uhbs.ch
Mueller-Brand
J
J
Maecke
H R
HR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001918:Brachytherapy / Q000379:methods*; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage
D000911:Antibodies, Monoclonal; D036361:Peptide Hormones