⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

Abstract

Vascular endothelial growth factor (VEGF)-A is overexpressed in most malignant and premalignant breast lesions. VEGF-A can be visualized noninvasively with PET imaging and using the tracer 89 Zr-labeled bevacizumab. In this clinical feasibility study, we assessed whether VEGF-A in primary breast cancer can be visualized by 89 Zr-bevacizumab PET. Methods: Before surgery, breast cancer patients underwent a PET/CT scan of the breasts and axillary regions 4 d after intravenous administration of 37 MBq of 89 Zr-bevacizumab per 5 mg. PET images were compared with standard imaging modalities. 89 Zr-bevacizumab uptake was quantified as the maximum standardized uptake value (SUV max ). VEGF-A levels in tumor and normal breast tissues were assessed with enzyme-linked immunosorbent assay. Data are presented as mean 6 SD. Results: Twenty-five of 26 breast tumors (mean size 6 SD, 25.1 6 19.8 mm; range, 4-80 mm) in 23 patients were visualized. SUV max was higher in tumors (1.85 6 1.22; range, 0.52-5.64) than in normal breasts (0.59 6 0.37; range, 0.27-1.69; P , 0.001). The only tumor not detected on PET was 10 mm in diameter. Lymph node metastases were present in 10 axillary regions; 4 could be detected with PET (SUV max , 2.66 6 2.03; range, 1.32-5.68). VEGF-A levels in the 17 assessable tumors were higher than in normal breast tissue in all cases (VEGF-A/mg protein, 184 6 169 pg vs. 10 6 21 pg; P 5 0.001), whereas 89 Zr-bevacizumab tumor uptake correlated with VEGF-A tumor levels (r 5 0.49). Conclusion: VEGF-A in primary breast cancer can be visualized by means of 89 Zr-bevacizumab PET.

PET-CT Imaging in Breast Cancer Patients: New Tracers, Future Directions

“…Nagengast et al reported similar results with 18 F-labeled ranibizumab, a Fab-fragment binding to VEGF [76,77], and also found good correlation between 89 Zr-bevacizumab uptake and therapeutic response to anti-angiogenic treatment in vivo in mouse-model with ovarian cancer xenografts [78]. The early experiences in breast cancer are also promising with Zrbevacizumab uptake in 26 breast cancer patients [79].…”

VEGF in nuclear medicine: Clinical application in cancer and future perspectives (Review)

“…In a study comparing the risks of radiation-induced cancer from mammography, molecular breast imaging, and positron emitting mammography, the cumulative cancer incidence is 15-30 times higher for positron emission mammography and molecular breast imaging than for mammography (113). The estimated radiation burden of 89Zr-bevacizumab-PET is 19 mSv per tracer injection, on the basis of extrapolation from 111 In-bevacizumab data and a dosimetry study on 89Zr-U36, compared with 5.3 mSv for 18 F-FDG PET (114)(115)(116)(117). Besides bevacizumab, other radiolabeled anti-VEGF antibodies such as I-labeled VG76e (118) and HuMV833 (119) have been reported.…”

Role of Positron Emission Tomography for the Monitoring of Response to Therapy in Breast Cancer

“…When labeled with 89-zirconium ( 89 Zr), bevacizumab preserves its VEGFbinding properties. 89 Zr-Bevacizumab tumor uptake correlated with VEGF tumor levels [108] andmight be valuable for prediction and evaluation of theeffect of VEGF-targetingtherapeutics.Inthe near future,the development of a PET/MRI integrated system will permit the combination of imaging of molecular targets using PET tracers and study of perfusion using MRI [109].…”