Radioimmunoscintigraphy and pre-treatment dosimetry of ¹³¹I-omburtamab for planning treatment of leptomeningeal disease

Abstract

Radiolabeled antibody treatment with ¹³¹I-omburtamab, administered intraventricularly into the CSF space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pre-treatment ¹³¹I-omburtamab imaging and dosimetric analysis in patients prior to therapy. Methods: Whole-body planar images were acquired at 3±1 h, 23±2 h, and 47±2 h after intracranioventricular administration of 75±5 MBq of ¹³¹I-omburtamab via an Ommaya reservoir. Multiple blood samples were also obtained for kinetic analysis. Separate regions of interest (ROI) were manually drawn to include the lateral ventricles and entire spinal canal CSF space and over the whole body. Count data in the ROI were corrected for background and physical decay, converted to activity and subsequently fitted to an exponential clearance function. Radiation-absorbed dose was estimated to the CSF, separately to the spinal column and ventricles as well as to the whole body and blood. Biodistribution of the injected radiolabeled antibody was assessed for all patients. Results: Ninety-five patients were included in the analysis. Biodistribution showed prompt localization in the ventricles and spinal CSF space with low systemic distribution, noted primarily as hepatic, renal, and bladder activity after the first day. Using ROI analysis, the effective half-lives were 13±11 h (range, 5-55 h) for CSF in the spinal column, 8±3 h (range, 3-17 h) for ventricles, and 41±1 (range, 23-81 h) for the whole body. Mean absorbed doses were 0.63±0.38 cGy/MBq (range, 0.24-2.25 cGy/MBq) for CSF in the spinal column, 1.03±0.69 cGy/MBq (range, 0.27-5.15 cGy/MBq) for the ventricular CSF, and 0.45±0.32 mGy/MBq (range, 0.05-1.43 mGy/MBq) for the whole body. Conclusion: Pre-therapeutic imaging with ¹³¹I-omburtamab allows for assessment of the biodistribution and dosimetry prior to administration of the therapeutic activity. Absorbed doses to the CSF compartments and whole body derived from the widely applicable serial ¹³¹I-omburtamab planar images were within acceptable agreement with previously reported data determined from serial ¹²⁴I-omburtamab positron emission tomography scans.