Tumors of the central nervous system are challenging to treat due to the limited effectiveness and associated toxicities of
chemotherapy and
radiation therapy. For
tumors that can be removed surgically, extent of malignant tissue resection has been shown to correlate with
disease progression, recurrence, and survival. Thus, improved technologies for real-time
brain tumor imaging are critically needed as tools for guided surgical resection. We previously engineered a novel
peptide that binds with high affinity and unique specificity to αVβ3, αVβ5, and α5β1
integrins, which are present on
tumor cells, and the vasculature of many
cancers, including
brain tumors. In the current study, we conjugated this engineered
peptide to a near infrared
fluorescent dye (Alexa Fluor 680), and used the resulting
molecular probe for non-invasive whole body imaging of patient-derived
medulloblastoma xenograft
tumors implanted in the cerebellum of mice. The engineered
peptide exhibited robust targeting and illumination of intracranial
medulloblastoma following both intravenous and
intraperitoneal injection routes. In contrast, a variant of the engineered
peptide containing a scrambled
integrin-binding sequence did not localize to
brain tumors, demonstrating that
tumor-targeting is driven by specific
integrin interactions. Ex vivo imaging was used to confirm the presence of
tumor and
molecular probe localization to the cerebellar region. These results warrant further clinical development of the engineered
peptide as a tool for image-guided resection of
central nervous system tumors.