Kimberley S Samkoe1,2,3, Hira S Sardar3, Brent D Bates4, Niki N Tselepidakis3, Jason R Gunn3, Kevin A Hoffer-Hawlik3, Joachim Feldwisch5, Brian W Pogue2,3, Keith D Paulsen2,3, Eric R Henderson4,6. 1. Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. 2. Department of Surgery, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. 3. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire. 4. Department of Orthaepedics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. 5. Affibody AB, Solna, Sweden. 6. Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Abstract
BACKGROUND AND OBJECTIVES: Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization. METHODS: Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. RESULTS: ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages. CONCLUSIONS: ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.
BACKGROUND AND OBJECTIVES: Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization. METHODS: Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. RESULTS: ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages. CONCLUSIONS: ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.
Authors: Alexander Stojadinovic; Denis H Y Leung; Axel Hoos; David P Jaques; Jonathan J Lewis; Murray F Brennan Journal: Ann Surg Date: 2002-03 Impact factor: 12.969
Authors: Gooitzen M van Dam; George Themelis; Lucia M A Crane; Niels J Harlaar; Rick G Pleijhuis; Wendy Kelder; Athanasios Sarantopoulos; Johannes S de Jong; Henriette J G Arts; Ate G J van der Zee; Joost Bart; Philip S Low; Vasilis Ntziachristos Journal: Nat Med Date: 2011-09-18 Impact factor: 53.440
Authors: Kimberley S Samkoe; Kristian Sexton; Kenneth M Tichauer; Shannon K Hextrum; Omar Pardesi; Scott C Davis; Julia A O'Hara; P Jack Hoopes; Tayyaba Hasan; Brian W Pogue Journal: Mol Imaging Biol Date: 2012-08 Impact factor: 3.488
Authors: Andrew J Aguirre; Nabeel Bardeesy; Manisha Sinha; Lyle Lopez; David A Tuveson; James Horner; Mark S Redston; Ronald A DePinho Journal: Genes Dev Date: 2003-12-17 Impact factor: 11.361
Authors: C Kersting; J Packeisen; B Leidinger; B Brandt; R von Wasielewski; W Winkelmann; P J van Diest; G Gosheger; H Buerger Journal: J Clin Pathol Date: 2006-02-03 Impact factor: 3.411
Authors: Rahul Pal; Marisa E Hom; Nynke S van den Berg; Thinzar M Lwin; Yu-Jin Lee; Andrey Prilutskiy; William Faquin; Eric Yang; Srinivas V Saladi; Mark A Varvares; Eben L Rosenthal; Anand T N Kumar Journal: Clin Cancer Res Date: 2022-06-01 Impact factor: 13.801
Authors: Cheng Wang; Xiaochun Xu; Margaret Folaron; Jason R Gunn; Sassan Hodge; Eunice Y Chen; P Jack Hoopes; Kenneth M Tichauer; Kimberley S Samkoe Journal: Mol Imaging Biol Date: 2021-10-14 Impact factor: 3.484
Authors: Jasper Vonk; Jaron G de Wit; Floris J Voskuil; Yang Hang Tang; Wouter T R Hooghiemstra; Matthijs D Linssen; Evert van den Broek; Jan J Doff; Sebastiaan A H J de Visscher; Kees-Pieter Schepman; Bert van der Vegt; Gooitzen M van Dam; Max J H Witjes Journal: J Nucl Med Date: 2021-09-16 Impact factor: 11.082
Authors: John Y K Lee; Steve S Cho; Walter Stummer; Janos L Tanyi; Alexander L Vahrmeijer; Eben Rosenthal; Barbara Smith; Eric Henderson; David W Roberts; Amy Lee; Constantinos G Hadjipanayis; Jeffrey N Bruce; Jason G Newman; Sunil Singhal Journal: J Biomed Opt Date: 2019-12 Impact factor: 3.170