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Brain cancer is a challenging disease to treat using conventional approaches. The present investigation aimed to develop a radiopharmaceutical targeting brain cancer based on natural isovanillin. Different parameters were optimized, resulting in high radiolabeling efficiency (97.3 ± 1.2%) and good stability (<48 h). The tracer was formulated for intranasal delivery in a chitosan nanoparticles system with a mean particle size of 141 ± 2 nm, a polydispersity index of 0.23 ± 0.02, and a zeta potential of -17.4 ± 0.3 mV to enhance nasal uptake and surmount the blood-brain barrier. The system was characterized and assessed in-vitro for suitability and specificity and evaluated in-vivo in normal and tumorized mice. The biodistribution profile in brain tumor showed 20.5 ± 0.4 %ID/g localization and cancer cell targeting within 60 min. Improvement in brain tumor uptake resulted from both the nanoformulation and nasal administration of iodoisovanillin. Overall, the reported results encourage the potential use of the nanoformulated labeled compound as an anticancer agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)