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
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Comparing monoclonal antibodies and small peptidic hormones for local targeting of malignant gliomas A. Merlo", J. Mueller-Brand", and H . R. Maecke/:" Neurosurgery, Departments of Surgery and Radiology, University Hospitals, Basel, Switzerland Medicine, Departm ents of Surgery and Radiolo gy, University Hospitals, Basel, Switzerland 3 Radiochemistry, Departments of Surgery and Radiology, University Hospitals, Basel, Switzerland 1
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Summary Monoclonal antibodies, F(ab ')z 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 tumo r cell clusters that migrate along vascular clefts and axonal pathwa ys. Tumor uptake was significantly improved by using small peptidic hormone receptor s, 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 intratumo ral injection by using these small drug-like radioconjugates. Rap id 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 radiopharm akon injected into the center of non-resected tumors. Distribut ion 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 radiopharm aceuticals into human invasive gliomas. Keywords: Local therap y; low-grade and high grade glioma; small regulatory peptidic vectors; tumor targeting ; radiolabelling; radiopept ide-brachytherapy .
Physical and radiobiological basis for locoregional radioimmuno- and radio peptide brachytherapy in glial brain tumors In 1898, immediately after the discovery of Radium and Polonium by Marie and Pierre Curie, the medical potential of radioactive decay was realized, especially for the treatment of cancer. Brain tumors have been treated for decades with radioactive implants or seeds,
often loaded with Iodine-125 (after-loading) [20], In radioimmuno- and radiopeptide brachytherapy, the most frequently used particles are electrons, negatively charged particles with a mass about 1840 times smaller than the mass of a proton. If produced by the decay of radioactive isotopes, electrons give rise to beta-rays, and isotopes releasing electrons are called beta-emitters. The do se rate is defined as the beam intensity which is a function of the number of electrons per second. Isotope activity is defined by the num
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