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Neuro-oncology

The potential of theragnostic ¹²⁴I-8H9 convection-enhanced delivery in diffuse intrinsic pontine glioma.


PMID 24526309

Abstract

Reasons for failure in prior human glioma convection-enhanced delivery (CED) clinical trials remain unclear. Concentration-dependent volume of distribution (Vd) measurement of CED-infused agents in the human brain is challenging and highlights a potential technical shortcoming. Activity of iodine isotope 124 ((124)I ) in tissue can be directly measured in vivo with high resolution via PET. With the potential therapeutic utility of radioimmunotherapy, we postulate (124)I conjugated to the antiglioma monoclonal antibody 8H9 may serve as a "theragnostic" agent delivered via CED to diffuse intrinsic pontine glioma. Fifteen rats underwent CED of 0.1-1.0 mCi of (131)I-8H9 to the pons for toxicity evaluation. Six additional rats underwent CED of 10 µCi of (124)I-8H9 to the pons for dosimetry, with serial microPET performed for 1 week. Two primates underwent CED of gadolinium-albumin and 1.0 mCi of (124)I-8H9 to the pons for safety and dosimetry analysis. Serial postoperative PET, blood, and CSF radioactivity counts were performed. One rat (1.0 mCi (131)I-8H9 infusion) suffered toxicity necessitating early sacrifice. PET analysis in rats yielded a pontine absorbed dose of 37 Gy/mCi. In primates, no toxicity was observed, and absorbed pontine dose was 3.8 Gy/mCi. Activity decreased 10-fold with 48 h following CED in both animal models. Mean Vd was 0.14 cc(3) (volume of infusion [Vi] to Vd ratio = 14) in the rat and 6.2 cc(3) (Vd/Vi = 9.5) in primate. The safety and feasibility of (124)I dosimetry following CED via PET is demonstrated, establishing a preclinical framework for a trial evaluating CED of (124)I-8H9 for diffuse intrinsic pontine glioma.