Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature

W. Cai, K. Chen, Z.-B. Li, S. S. Gambhir, X. Chen
2007 Journal of Nuclear Medicine  
To date, the in vivo imaging of quantum dots (QDs) has been mostly qualitative or semiquantitative. The development of a dual-function PET/near-infrared fluorescence (NIRF) probe can allow for accurate assessment of the pharmacokinetics and tumor-targeting efficacy of QDs. Methods: A QD with an aminefunctionalized surface was modified with RGD peptides and 1,4,7,10-tetraazacyclodocecane-N,N9,N$,N%-tetraacetic acid (DOTA) chelators for integrin a v b 3 -targeted PET/NIRF imaging. A cell-binding
more » ... ssay and fluorescence cell staining were performed with U87MG human glioblastoma cells (integrin a v b 3positive). PET/NIRF imaging, tissue homogenate fluorescence measurement, and immunofluorescence staining were performed with U87MG tumor-bearing mice to quantify the probe uptake in the tumor and major organs. Results: There are about 90 RGD peptides per QD particle, and DOTA-QD-RGD exhibited integrin a v b 3 -specific binding in cell cultures. The U87MG tumor uptake of 64 Cu-labeled DOTA-QD was less than 1 percentage injected dose per gram (%ID/g), significantly lower than that of 64 Culabeled DOTA-QD-RGD (2.2 6 0.3 [mean 6 SD] and 4.0 6 1.0 %ID/g at 5 and 18 h after injection, respectively; n 5 3). Taking into account all measurements, the liver-, spleen-, and kidney-tomuscle ratios for 64 Cu-labeled DOTA-QD-RGD were about 100:1, 40:1, and 1:1, respectively. On the basis of the PET results, the U87MG tumor-to-muscle ratios for DOTA-QD-RGD and DOTA-QD were about 4:1 and 1:1, respectively. Excellent linear correlation was obtained between the results measured by in vivo PET imaging and those measured by ex vivo NIRF imaging and tissue homogenate fluorescence (r 2 5 0.93). Histologic examination revealed that DOTA-QD-RGD targets primarily the tumor vasculature through an RGD-integrin a v b 3 interaction, with little extravasation. Conclusion: We quantitatively evaluated the tumor-targeting efficacy of a dual-function QD-based probe with PET and NIRF imaging. This dual-function probe has significantly reduced potential toxicity and overcomes the tissue penetration limitation of optical imaging, allowing for quantitative targeted imaging in deep tissue.
doi:10.2967/jnumed.107.043216 pmid:17942800 fatcat:hq4fiuj3jrdm3gtdywaqox6gla