Fluorescence lifetime imaging to differentiate bound from unbound ICG-cRGD both in vitro and in vivo

PL Stegehuis, MC Boonstra, KE de Rooij, FE Powolny, R Sinisi, HAR Homulle, C Bruschini, E Charbon, CJH van de Velde, B.P.F. Lelieveldt, AL Vahrmeijer, J Dijkstra, M Giessen

Research output: Chapter in Book/Conference proceedings/Edited volumeConference contributionScientificpeer-review

6 Citations (Scopus)

Abstract

 Excision of the whole tumor is crucial, but remains difficult for many tumor types. Fluorescence lifetime imaging could be helpful intraoperative to differentiate normal from tumor tissue. In this study we investigated the difference in fluorescence lifetime imaging of indocyanine green coupled to cyclic RGD free in solution/serum or bound to integrins e.g. in tumors. The U87-MG glioblastoma cell line, expressing high integrin levels, was cultured to use in vitro and to induce 4 subcutaneous tumors in a-thymic mice (n=4). Lifetimes of bound and unbound probe were measured with an experimental time-domain single-photon avalanche diode array (time resolution <100ps). In vivo measurements were taken 30-60 minutes after intravenous injection, and after 24 hours. The in vitro lifetime of the fluorophores was similar at different concentrations (20, 50 and 100μM) and showed a statistically significant higher lifetime (p<0.001) of bound probe compared to unbound probe. In vivo, lifetimes of the fluorophores in tumors were significantly higher (p<0.001) than at the control site (tail) at 30-60 minutes after probe injection. Lifetimes after 24 hours confirmed tumor-specific binding (also validated by fluorescence intensity images). Based on the difference in lifetime imaging, it can be concluded that it is feasible to separate between bound and unbound probes in vivo. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).
Original languageEnglish
Title of host publicationAdvanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XIII
EditorsAnita Mahadevan-Jansen, Tuan Vo-Dinh, Warren S. Grundfest
Place of PublicationBellingham, WA
PublisherSPIE
Pages1-6
Number of pages6
ISBN (Print)978-162841403-5
DOIs
Publication statusPublished - 2015
Externally publishedYes
EventAdvanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XIII - San Francisco, CA, United States
Duration: 8 Feb 201510 Feb 2015

Publication series

NameProceedings of SPIE- International Society for Optical Engineering
Volume9313
ISSN (Print)0277-786X
ISSN (Electronic)1605-7422

Conference

ConferenceAdvanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XIII
Country/TerritoryUnited States
CitySan Francisco, CA
Period8/02/1510/02/15

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