Abstract 4213: Gold nanostar as theranostic probe for brain tumor sensitive PET-optical imaging and image-guided specific photothermal therapy
Authors: Liu Yang , Carpenter Austin , Yuan Hsiangkuo , Zhou Zhengyuan , Zalutsky Michael , Vaidyanathan Ganesan , Yan Hai , Vo-Dinh Tuan 
Published: July 2016

Malignant brain tumors are one of the most lethal cancer forms causing over 14,000 deaths each year. In spite of extensive research efforts over many decades, the median overall survival (OS) still remains at just 15 months for the common malignant giloma, glioblastoma multiforme (GBM). We have developed a multifunctional gold nanostar (GNS) probe that shows potential to improve cancer management by providing personalized cancer theranostics, a combination of diagnostic and therapeutic functions. The GNS nanoprobe has a tunable plasmon absorption peak in the near infrared (NIR) “tissue optical window” for deep-tissue penetration and tip-enhanced surface plasmon resonance, which makes the GNS as a superior nanoprobe for cancer detection using surface-enhanced Raman spectroscopy (SERS), two-photon photoluminescence (TPL) imaging and photothermal therapy with NIR light. We have also functionalized the GNS with iodine-124 radioisotopes for sensitive 3D positron emission tomography (PET) and achieved a 10-picomolar limit of detection (LOD). The GNS nanoprobe accumulates selectively in brain tumor due to the enhanced permeability and retention (EPR) effect, which is caused by defective endothelial tight junctions in blood vessels surrounding the tumor. On the contrary, the GNS nanoprobe has minimum uptake in normal brain tissue due to the intact blood-brain-barrier (BBB). The GNS uptake ratio of tumor-to-normal (T/N) brain tissue is measured to be up to 30:1 by using inductively coupled plasma mass spectrometry (ICP-MS). By combining the high detection sensitivity of PET imaging and specific accumulation of GNS in brain tumor, we have demonstrated the feasibility of 1-mm brain tumor detection with the I-124 labeled GNS nano radiotracer. The obtained T/N ratio is up to 10:1 with our GNS nanoprobe labeled with I-124, which is much better than that (typically less than 1.5:1) for traditional F-18 fluorodeoxyglucose (FDG) PET contrast agent due to high glucose uptake in normal brain tissue. Furthermore, we have utilized GNS's high TPL intensity to delineate brain tumor margin with excellent sensitivity and high spatial resolution (μm level). In addition to brain tumor imaging, we have successfully demonstrated photothermal ablation with a NIR laser taking advantage of GNS's superior photothermal conversion efficiency. We have also performed a 6-month toxicity study for the GNS nanoprobe and experiment results, including body weight monitoring, blood chemistry test, and H&E histopathology examination, show no deleterious effect after infusion of GNS nanoprobe up to 100 mg/kg dose. In summary, the GNS nanoprobe, with limited toxicity and multifunctional capabilities, exhibits great promise to fulfill the unmet needs in brain tumor management in future translational medicine investigations.

Citation Format: Yang Liu, Austin Carpenter, Hsiangkuo Yuan, Zhengyuan Zhou, Michael Zalutsky, Ganesan Vaidyanathan, Hai Yan, Tuan Vo-Dinh. Gold nanostar as theranostic probe for brain tumor sensitive PET-optical imaging and image-guided specific photothermal therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4213.