MicroPET/CT Imaging of AXL Downregulation by HSP90 Inhibition in Triple-Negative Breast Cancer

Figure 4

Effect of 17-AAG on AXL in xenograft MDA-MB-231 tumors assessed by microPET/CT imaging and ex vivo autoradiography and radiotracer biodistribution in mice. (a) Representative microPET/CT images of MDA-MB-231 tumor xenografts in mice 24 h after intravenous injection of ⁶⁴Cu-anti-hAXL. One group of mice received a daily intraperitoneal injection of 17-AAG at a dose of 60 mg/kg in 200 µL of DMSO in PBS (128 : 72, v/v) for 9 days before imaging ( = 3). Mice in the control group received daily intraperitoneal injections of the same volume of 128 : 72 DMSO/PBS vehicle ( = 3) for 9 days before imaging. The tumor uptake of ⁶⁴Cu-anti-hAXL in the 17-AAG treatment group was perceptibly lower than that in the vehicle-treated control group (left). White arrows: tumors. MIP: maximal intensity projection. Quantitative VOI analysis of tumor uptake on microPET/CT images (right). The tumor uptake of ⁶⁴Cu-anti-hAXL was 44% lower in the 17-AAG treatment group than in the vehicle control group (SUV: 78.32 ± 5.02 versus 140.00 ± 3.73, < 0.0001). (b) Autoradiographs of representative MDA-MB-231 tumor sections from vehicle-treated control mice and 17-AAG-treated mice obtained 24 h after intravenous injection of ⁶⁴Cu-anti-hAXL. (c) Biodistribution of radiotracer 24 h after intravenous injection of ⁶⁴Cu-anti-hAXL in vehicle-treated control mice and 17-AAG–treated mice ( = 3/group). The tumor uptake of radiotracer was 49% lower in the 17-AAG treatment group than in the vehicle control group (4.74 ± 1.01 versus 9.31 ± 3.46 %ID/g, = 0.01).

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