| Autor: |
Li X; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Song W; Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China., Engle JW; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Mixdorf JC; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Barnhart TE; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Sun Y; Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States., Zhu Y; Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States., Cai W; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin 53792, United States. |
| Abstrakt: |
CD93 is overexpressed in multiple solid tumor types, serving as a novel target for antiangiogenic therapy. The goal of this study was to develop a 64 Cu-based positron emission tomography (PET) tracer for noninvasive imaging of CD93 expression. Antimouse-CD93 mAb (mCD93) and the CD93 ligand IGFBP7 were conjugated to a bifunctional chelator, p -isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid ( p -SCN-NOTA) and labeled with 64 Cu. To evaluate the pharmacokinetic properties and tumor-targeting efficacy of [ 64 Cu]Cu-NOTA-mCD93 and [ 64 Cu]Cu-NOTA-IGFBP7, PET imaging and biodistribution were performed on both 4T1 murine breast tumor-bearing mice and MDA-MB-231 human breast tumor-bearing mice. The tumor model HT1080-FAP, which does not overexpress CD93, was used as a negative control. Fluorescent immunostaining was conducted on different tissues to correlate radiotracer uptake with CD93 expression. 64 Cu-labeling was achieved with high yield and specific activity. Serial PET imaging revealed that the in vivo performance of [ 64 Cu]Cu-NOTA-IGFBP7 was superior to that of [ 64 Cu]Cu-NOTA-mCD93, and that the tracer [ 64 Cu]Cu-NOTA-IGFBP7 exhibited elevated tumor uptake values and excellent tumor retention in MDA-MB-231 mice, rather than in 4T1 murine mice. The MDA-MB-231 tumor uptake of [ 64 Cu]Cu-NOTA-IGFBP7 was 2.85 ± 0.15, 3.69 ± 0.60, 6.91 ± 0.88, and 6.35 ± 0.55%ID/g at 1, 4, 24, and 48 h p.i., respectively, which were significantly higher than that in the CD93-negative HT1080-FAP tumor (0.73 ± 0.15, 0.97 ± 0.31, 1.00 ± 0.07, and 1.02 ± 0.11%ID/g, respectively). The significant difference between positive and negative tumors indicated [ 64 Cu]Cu-NOTA-IGFBP7 was specifically binding to CD93. Biodistribution data as measured by gamma counting were consistent with the PET analysis. Ex vivo histology further confirmed the high CD93 expression on MDA-MB-231 tumor tissues. Herein, we prepared two novel radiotracers, [ 64 Cu]Cu-NOTA-mCD93 and [ 64 Cu]Cu-NOTA-IGFBP7, for the first immune-PET imaging of CD93 expression. Our results suggest that [ 64 Cu]Cu-NOTA-IGFBP7 is a more potential radiotracer for visualizing angiogenesis due to its sensitive, persistent, and CD93-specific characteristics. |
