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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 3/2018

01-06-2018 | Brief Article

Improved Debulking of Peritoneal Tumor Implants by Near-Infrared Fluorescent Nanobody Image Guidance in an Experimental Mouse Model

Authors: Pieterjan Debie, Marian Vanhoeij, Natalie Poortmans, Janik Puttemans, Kris Gillis, Nick Devoogdt, Tony Lahoutte, Sophie Hernot

Published in: Molecular Imaging and Biology | Issue 3/2018

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Abstract

Purpose

Debulking followed by combination chemotherapy is currently regarded as the most effective treatment for advanced ovarian cancer. Prognosis depends drastically on the degree of debulking. Accordingly, near-infrared (NIR) fluorescence imaging has been proposed to revolutionize cancer surgery by acting as a sensitive, specific, and real-time tool enabling visualization of cancer lesions. We have previously developed a NIR-labeled nanobody that allows fast, specific, and high-contrast imaging of HER2-positive tumors. In this study, we applied this tracer during fluorescence-guided surgery in a mouse model and investigated the effect on surgical efficiency.

Procedures

0.5 × 106 SKOV3.IP1-Luc+ cells were inoculated intraperitoneally in athymic mice and were allowed to grow for 30 days. Two nanomoles of IRDye800CW-anti-HER2 nanobody was injected intravenously. After 1h30, mice were killed, randomized in two groups, and subjected to surgery. In the first animal group (n = 7), lesions were removed by a conventional surgical protocol, followed by excision of remaining fluorescent tissue using a NIR camera. The second group of mice (n = 6) underwent directly fluorescence-guided surgery. Bioluminescence imaging was performed before and after surgery. Resected tissue was categorized as visualized during conventional surgery or not, fluorescent or not, and bioluminescent positive or negative.

Results

Fluorescence imaging allowed clear visualization of tumor nodules within the abdomen, up to submillimeter-sized lesions. Fluorescence guidance resulted in significantly reduced residual tumor as compared to conventional surgery. Moreover, sensitivity increased from 59.3 to 99.0 %, and the percentage of false positive lesions detected decreased from 19.6 to 7.1 %.

Conclusions

This study demonstrates the advantage of intraoperative fluorescence imaging using nanobody-based tracers on the efficiency of debulking surgery.
Appendix
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Literature
1.
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403CrossRefPubMed
2.
Bray F, Ren JS, Masuyer E, Ferlay J (2013) Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 132:1133–1145CrossRefPubMed
3.
Prat J (2014) Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynecol Obstet 124:1–5CrossRef
4.
5.
Schorge JO, McCann C, Del Carmen MG (2010) Surgical debulking of ovarian cancer: what difference does it make? Rev Obstet Gynecol 3:111–117PubMedPubMedCentral
6.
Pereira A, Pérez-Medina T, Magrina JF et al (2016) The impact of debulking surgery in patients with node-positive epithelial ovarian cancer: analysis of prognostic factors related to overall survival and progression-free survival after an extended long-term follow-up period. Surg Oncol 25:49–59CrossRefPubMed
7.
Lim MC, Seo S-S, Kang S et al (2012) Intraoperative image-guided surgery for ovarian cancer. Quant Imaging Med Surg 2:114–117PubMedPubMedCentral
8.
Wallace S, Kumar A, Mc M et al (2017) Efforts at maximal cytoreduction improve survival in ovarian cancer patients, even when complete gross resection is not feasible. Gynecol Oncol 145:21–26CrossRefPubMed
9.
10.
11.
van Dam GM, Themelis G, Crane LMA et al (2011) Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med 17:1315–1319CrossRefPubMed
12.
Hoogstins CES, Tummers QRJG, Gaarenstroom KN et al (2016) A novel tumor-specific agent for intraoperative near-infrared fluorescence imaging: a translational study in healthy volunteers and patients with ovarian cancer. Clin Cancer Res 22:2929–2938CrossRefPubMed
13.
Tipirneni KE, Warram JM, Moore LS et al (2017) Oncologic procedures amenable to fluorescence-guided surgery. Ann Surg 266:36–47CrossRefPubMed
14.
Rosenthal EL, Moore LS, Tipirneni K et al (2017) Sensitivity and specificity of cetuximab-IRDye800CW to identify regional metastatic disease in head and neck cancer. Clin Cancer Res 23:4744–4752CrossRefPubMed
15.
Lamberts LE, Koch M, de Jong JS, et al (2016) Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: a phase I feasibility study. Clin Cancer Res
16.
17.
De Vos J, Devoogdt N, Lahoutte T, Muyldermans S (2013) Camelid single-domain antibody-fragment engineering for (pre)clinical in vivo molecular imaging applications: adjusting the bullet to its target. Expert Opin Biol Ther 13:1149–1160CrossRefPubMed
18.
Hamers-Casterman C, Atarhouch T, Muyldermans S et al (1993) Naturally occurring antibodies devoid of light chains. Nature 363:446–448CrossRefPubMed
19.
Kijanka M, Warnders F-J, El Khattabi M et al (2013) Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery. Eur J Nucl Med Mol Imaging 40:1718–1729CrossRefPubMed
20.
Debie P, Van Quathem J, Hansen I et al (2017) Effect of dye and conjugation chemistry on the biodistribution profile of near-infrared-labeled nanobodies as tracers for image-guided surgery. Mol Pharm 14:1145–1153CrossRefPubMed
21.
Broisat A, Hernot S, Toczek J et al (2012) Nanobodies targeting mouse/human VCAM1 for the nuclear imaging of atherosclerotic lesions. Circ Res 110:927–937CrossRefPubMedPubMedCentral
22.
Keyaerts M, Xavier C, Heemskerk J et al (2016) Phase I study of 68Ga-HER2-nanobody for PET/CT assessment of HER2 expression in breast carcinoma. J Nucl Med 57:27–33CrossRefPubMed
23.
Blykers A, Schoonooghe S, Xavier C et al (2015) PET imaging of macrophage mannose receptor-expressing macrophages in tumor stroma using 18F-radiolabeled camelid single-domain antibody fragments. J Nucl Med 56:1265–1271CrossRefPubMed
24.
25.
Steeland S, Vandenbroucke RE, Libert C (2016) Nanobodies as therapeutics: big opportunities for small antibodies. Drug Discov Today 21:1076–1113CrossRefPubMed
26.
De Vlieghere E, Carlier C, Ceelen W et al (2016) Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers. Data Brief 6:542–549CrossRefPubMedPubMedCentral
27.
Keyaerts M, Verschueren J, Bos TJ et al (2008) Dynamic bioluminescence imaging for quantitative tumour burden assessment using IV or IP administration of d-luciferin: effect on intensity, time kinetics and repeatability of photon emission. Eur J Nucl Med Mol Imaging 35:999–1007CrossRefPubMed
28.
29.
30.
Harlaar NJ, Kelder W, Sarantopoulos A et al (2013) Real-time near infrared fluorescence (NIRF) intra-operative imaging in ovarian cancer using an αvβ3-integrin targeted agent. Gynecol Oncol 128:590–595CrossRefPubMed
31.
Handgraaf HJM, Boonstra MC, Prevoo HAJM et al (2017) Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for intraoperative visualization of multiple cancer types. Oncotarget 8:21054–21066CrossRefPubMed
32.
Day KE, Beck LN, Deep NL et al (2013) Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma. Laryngoscope 123:2681–2689CrossRefPubMed
33.
Christensen A, Juhl K, Persson M et al (2017) uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model. Oncotarget 8:20519–20520CrossRef
34.
Metildi CA, Kaushal S, Snyder CS et al (2013) Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model. J Surg Res 179:87–93CrossRefPubMed
35.
Sexton K, Tichauer K, Samkoe KS et al (2013) Fluorescent affibody peptide penetration in glioma margin is superior to full antibody. PLoS One 8:1–9CrossRef
36.
English DP, Roque DM, Santin AD (2013) HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Mol Diagn Ther 17:85–99CrossRefPubMedPubMedCentral
37.
38.
van Oosten M, Crane LMA, Bart J et al (2011) Selecting potential targetable biomarkers for imaging purposes in colorectal cancer using target selection criteria (TASC): a novel target identification tool. Transl Oncol 4:71–82CrossRefPubMedPubMedCentral
39.
Hoogstins CES, Weixler B, Boogerd LSF et al (2017) In search for optimal targets for intraoperative fluorescence imaging of peritoneal metastasis from colorectal cancer. Biomark Cancer 9:1–7
40.
Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9:123–128CrossRefPubMed
41.
Brouwer OR, Buckle T, Bunschoten A et al (2012) Image navigation as a means to expand the boundaries of fluorescence-guided surgery. Phys Med Biol 57:3123–3136CrossRefPubMed
42.
Buckle T, van Leeuwen AC, Chin PTK et al (2010) A self-assembled multimodal complex for combined pre- and intraoperative imaging of the sentinel lymph node. Nanotechnology 21:355101 (9pp)CrossRefPubMed
43.
44.
Metadata
Title
Improved Debulking of Peritoneal Tumor Implants by Near-Infrared Fluorescent Nanobody Image Guidance in an Experimental Mouse Model
Authors
Pieterjan Debie
Marian Vanhoeij
Natalie Poortmans
Janik Puttemans
Kris Gillis
Nick Devoogdt
Tony Lahoutte
Sophie Hernot
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 3/2018
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-017-1134-2

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