Evaluation of ¹²⁴I-NM404 as a universal agent for the detection and surveillance of intracranial malignancies.

B10

Objectives: Gliomas are uniformly lethal with average survival following diagnosis of 12 to 18 months. Biological markers coupled with techniques in molecular imaging might aid to selectively visualize intracranial gliomas. This new feasibility is important in the diagnoses, treatment, and surveillance of these lethal tumors. NM404, a novel phospholipid ether analog currently in clinical Phase 1 trials for human lung cancer, demonstrates striking tumor avidity in 32 rodent models of human cancer. The primary aim of this study was to examine the multi-modal imaging characteristics of intracranial rat gliomas by comparing ¹²⁴I-NM404 with microPET and microCT against the current gold standard of gadolinium enhanced microMRI. Secondary aims are to evaluate signal to background noise in tumor versus normal brain tissue, and corroborate imaging with histology. Our goal is to determine whether NM404 might be useful in the treatment of patients with gliomas. Methods: The frontal lobes of five Fischer rats weighing between 125-150g were inoculated with 1.5x10⁶ RG2 rat glioma cells in 5ul of methylcellulose. Seven days after inoculation, ¹²⁴I-NM404 was injected intravenously (80-100μCi/0.2ml) into rats bearing tumors with maximum diameters of 7-12mm. Serial PET scans were obtained at 6, 12, 24, 48, 96 hours and at 12 days. Signal intensity was assessed by comparing the tumor-bearing side to the opposite hemisphere in the same animal. All five rats displayed signs of neurological deterioration by 12 days after inoculation. Animals were scanned using PET, MRI with gadolinium and CT and then sacrificed. Brains were harvested, digitally photographed and sent for histological analysis including microglial studies in another laboratory. Results: ¹²⁴I-NM404 with PET provided a more accurate image of the tumor than MRI with gadolinium indicating the new imaging modality is better than the current gold standard. Fused CT and PET images provided an accurate three-dimensional anatomical model. NM404 uptake corresponded to tumor location by histology. Tumor signal intensity was significantly higher than background and persisted for 12 days after inoculation. Uptake of NM404 tightly correlated with tumor location as determined by histology. Interestingly, the number of viable cells within a tumor appeared to decline, indicating radiolabeled NM404 might have a therapeutic effect. Conclusion: Preliminary results indicate NM404 displays an intense avidity to gliomas. ¹²⁴I-NM404 might have utility in diagnoses, treatment and surveillance of gliomas. Further studies utilizing ¹²⁵I and ¹²⁴I with NM404 need to be completed in order to fully characterize the imaging and therapeutic potential prior to clinical application.