VEGF-SPECT with 111In-bevacizumab in stage III/IV melanoma patients

Nagengast, Wouter B.; Hooge, Marjolijn N. Lub-de; Straten, Esther M. E. van; Kruijff, Schelto; Brouwers, Adrienne H.; Dunnen, Wilfred F. A. den; Jong, Johan R. de; Hollema, Harry; Dierckx, Rudi; Mulder, Nanno; Vries, Elisabeth G.E. de; Hoekstra, Harald J.; Hospers, Geke A.P.

doi:10.1016/j.ejca.2011.02.009

Cited by 50 publications

(45 citation statements)

References 36 publications

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“…In a xenograft mouse model, we have shown that tumor accumulation of 89 Zr-bevacizumab increases in time, whereas uptake in normal organs decreases (6). This increase in 89 Zr-bevacizumab tumor accumulation over time was also shown in melanoma patients who underwent 111 In-bevacizumab SPECT (9). In a human SKOV-3 ovarian tumor xenograft, there was higher uptake of 89 Zr-bevacizumab than of 89 Zr-IgG (6), indicating tumorspecific uptake.…”

Section: Discussionmentioning

confidence: 76%

“…Patients received 37 MBq of 89 Zr-bevacizumab per 5 mg of protein as an intravenous bolus injection 4 d before PET scanning and were observed for allergic reactions for 1 h. The 5-mg dose of bevacizumab was chosen because this was the lowest possible dose that was reproducible during the labeling procedure. The same dose was used in a study with 111 In-labeled bevacizumab, which visualized all known melanoma lesions (9). 89 Zr has a decay half-life of 78.4 h, the mean b-energy is 395.5 keV, the positron branching fraction is 22.74%, and the main g-emissions are 511 keV, 45.5%, and 909 keV, 99.04%.…”

Section: Patientsmentioning

confidence: 99%

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⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 76%

Section: Patientsmentioning

confidence: 99%

⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

et al. 2013

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“…In particular, the mAb bevacizumab is one of the most studied radiolabelled anti-VEGF drugs and, to date, it has been labeled with a number of PET isotopes such 89Zr (94), 124I (95), 86Y (96), and 64Cu (97). In addition, it has also been investigated with various other imaging techniques such as single photon emission computed tomography (SPECT) (98), ultrasound (99), and optical imaging (100). Studies with radiolabeled bevacizumab for imaging tumor angiogenesis were performed in preclinical models proposing that its accumulation in the tumor was due to interactions with the VEGF-A-165 and -189 isoforms, associated with the tumor cell surface and/or the extracellular matrix (101,102).…”

Section: Targeting Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

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

Taurone

Galli²,

Agostinelli

et al. 2016

International Journal of Oncology

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“…For this purpose, the BevF(ab9) 2 probe targeting VEGF was designed using the F(ab9) 2 fragment of the anti-VEGF antibody bevacizumab. Bevacizumab has been labeled with various radioisotopes for PET and SPECT imaging of VEGF expression (16)(17)(18)(19)(20). One limitation of using intact antibodies for molecular imaging is the long half-life and propensity to accumulate in the liver due to a high molecular weight (21,22).…”

Section: Discussionmentioning

confidence: 99%

Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models

et al. 2014

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Epidermal growth factor receptor (EGFR) expression is upregulated in many types of tumors, and the EGFR tyrosine kinase inhibitor gefitinib has high potential as an anticancer drug. However, accumulating clinical evidence has indicated that only a subset of patients benefit from gefitinib treatment. This study aimed to determine whether optical imaging of vascular endothelial growth factor (VEGF) expression can be an early biomarker for tumor response to gefitinib therapy. Methods: A VEGF-targeting fluorescent probe Dye-BevF(ab′) 2 was prepared and tested in vivo. Longitudinal optical imaging studies using Dye-BevF(ab′) 2 were performed in both 22B (gefitinib-resistant) and A549 (gefitinib-responsive) tumor models at different times (days 0, 2, and 5) before and after gefitinib treatment. The imaging results were validated by ex vivo immunofluorescence staining and enzymelinked immunosorbent assay. Results: Dye-BevF(ab′) 2 exhibited high specificity for VEGF in vivo. There was no significant change in the Dye-BevF(ab′) 2 uptake in gefitinib-treated 22B tumors, compared with the control group. In contrast, the A549 tumor uptake of DyeBevF(ab′) 2 in the gefitinib-treated group was significantly lower on days 2 and 5 than that in the control group and at the baseline. An in vivo gefitinib treatment study confirmed that 22B tumors were gefitinibresistant, whereas A549 tumors were gefitinib-responsive. Immunofluorescence staining and enzyme-linked immunosorbent assay confirmed that changes in the Dye-BevF(ab′) 2 uptake were correlated with VEGF expression levels in tumors. Conclusion: Optical imaging of VEGF expression with Dye-BevF(ab′) 2 can be used for the early assessment of tumor response to gefitinib therapy. This approach may also be valuable for preclinical high-throughput screening of novel antiangiogenic drugs.

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VEGF-SPECT with 111In-bevacizumab in stage III/IV melanoma patients

Cited by 50 publications

References 36 publications

⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

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

Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models

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VEGF-SPECT with 111In-bevacizumab in stage III/IV melanoma patients

Cited by 50 publications

References 36 publications

89Zr-Bevacizumab PET Imaging in Primary Breast Cancer

89Zr-Bevacizumab PET Imaging in Primary Breast Cancer

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

Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models

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Product

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⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer