title: Shifting focus in optical image-guided cancer therapy.
abstract: Cancer patients could benefit from a surgical procedure that helps the surgeon to determine adequate tumor resection margins. Systemic injection of tumor-specific fluorescence agents with subsequent intraoperative optical imaging can guide the surgeon in this process. However, tumor heterogeneity hampers tumor-specific targeting. In addition, determination of adequate resection margins can be very challenging due to invasive tumor strands that are difficult to resolve and because of the confounding effect of variations in tissue optical properties in the surgical margin. We provide an overview of the "classic approach" of imaging tumor-specific targets or tumor-associated pathophysiological processes, and explain the limitations of these targeting strategies. It is proposed that problems of tumor heterogeneity can theoretically be circumvented by shifting focus of tumor targeting towards the follicle-stimulating hormone receptor (FSHR). Furthermore, we discuss why objective determination of resection margins is required to improve resection of the invasive strands, a goal that may be achieved by targeting the FSHR. When invasive strands would nevertheless extend beyond such a standardized resection margin, we suggest that adjuvant photodynamic therapy would be a very suitable therapeutic regimen. Finally, we describe how point optical spectroscopy can be used to scrutinize suspect tissue that is difficult to differentiate from normal tissue by measuring the local tissue optical properties to recover a local intrinsic fluorescence measurement.
authors.affiliation: Department of Molecular Imaging, Leiden University Medical Center, Leiden, The Netherlands, s.keereweer@erasmusmc.nl.
authors.forename: Stijn
authors.initials: S
authors.lastname: Keereweer
authors.forename: Pieter B A A
authors.initials: PB
authors.lastname: Van Driel
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Robinson
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Lowik
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D061848:Optical Imaging / Q000379:methods*; D009928:Organ Specificity
references.citation: Br J Cancer. 2011 Nov 8;105(10):1512-21
references.pmid: 21989183
references.citation: Head Neck Pathol. 2013 Sep;7(3):211-23
references.pmid: 23250819
references.citation: N Engl J Med. 2010 Oct 21;363(17):1621-30
references.pmid: 20961245
references.citation: Cell. 1996 Aug 9;86(3):353-64
references.pmid: 8756718
references.citation: Ann N Y Acad Sci. 1998 Feb 9;838:29-45
references.pmid: 9511793
references.citation: Cell. 2011 Nov 23;147(5):992-1009
references.pmid: 22118458
references.citation: Opt Lett. 2011 Aug 1;36(15):2791-3
references.pmid: 21808314
references.citation: J Biophotonics. 2009 Feb;2(1-2):29-36
references.pmid: 19343683
references.citation: Int J Cancer. 2012 Oct 1;131(7):1633-40
references.pmid: 22234729
references.citation: Mol Imaging Biol. 2013 Oct;15(5):560-8
references.pmid: 23619897
references.citation: Adv Drug Deliv Rev. 2011 Mar 18;63(3):136-51
references.pmid: 20441782
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-892
references.pmid: 22397650
references.citation: Nat Rev Cancer. 2006 Jul;6(7):535-45
references.pmid: 16794636
references.citation: Mol Imaging. 2010 Oct;9(5):237-55
references.pmid: 20868625
references.citation: Nat Chem Biol. 2007 Oct;3(10):668-77
references.pmid: 17828252
references.citation: Int J Cancer. 2011 Apr 15;128(8):1852-9
references.pmid: 20568113
references.citation: Nat Rev Cancer. 2011 Jan;11(1):9-22
references.pmid: 21160525
references.citation: Trends Mol Med. 2012 Jan;18(1):13-26
references.pmid: 22177734
references.citation: Am J Pathol. 2006 Oct;169(4):1415-26
references.pmid: 17003496
references.citation: Mol Imaging Biol. 2011 Apr;13(2):199-207
references.pmid: 20617389
references.citation: J Biomed Opt. 2009 Nov-Dec;14(6):064012
references.pmid: 20059250
references.citation: Cancer Res. 1996 Jun 1;56(11):2488-92
references.pmid: 8653682
references.citation: Nature. 2008 Apr 3;452(7187):580-9
references.pmid: 18385732
references.citation: Nat Methods. 2010 Aug;7(8):603-14
references.pmid: 20676081
references.citation: J Biomed Opt. 2008 Sep-Oct;13(5):054051
references.pmid: 19021431
references.citation: Opt Lett. 2012 Jun 1;37(11):1838-40
references.pmid: 22660046
references.citation: Nat Med. 1995 Jan;1(1):27-31
references.pmid: 7584949
references.citation: Arch Otolaryngol Head Neck Surg. 2011 Jun;137(6):609-15
references.pmid: 21690514
references.citation: Clin Gastroenterol Hepatol. 2012 Dec;10(12):1335-41
references.pmid: 23059052
references.citation: Photochem Photobiol Sci. 2011 Jul;10(7):1097-109
references.pmid: 21547329
references.citation: Mol Imaging Biol. 2010 Oct;12(5):488-99
references.pmid: 19960268
references.citation: Biomed Opt Express. 2012 Oct 1;3(10):2452-64
references.pmid: 23082287
references.citation: Biomed Opt Express. 2011 Jun 1;2(6):1687-702
references.pmid: 21698029
references.citation: Bioconjug Chem. 2010 May 19;21(5):797-802
references.pmid: 20397686
references.citation: Curr Opin Chem Biol. 2003 Oct;7(5):626-34
references.pmid: 14580568
references.citation: Sci Rep. 2012;2:798
references.pmid: 23152935
references.citation: Nat Med. 2011 Sep 18;17(10):1315-9
references.pmid: 21926976
references.citation: Anticancer Agents Med Chem. 2012 Jun;12(5):500-25
references.pmid: 22292760
references.citation: CA Cancer J Clin. 2011 Jul-Aug;61(4):250-81
references.pmid: 21617154
references.citation: Biomed Opt Express. 2013 Apr 09;4(5):696-708
references.pmid: 23667786
references.citation: Br J Surg. 2002 Aug;89(8):1008-13
references.pmid: 12153626
references.citation: Opt Lett. 2011 Aug 1;36(15):2997-9
references.pmid: 21808384
references.citation: Clin Cancer Res. 2010 May 15;16(10):2833-44
references.pmid: 20410058
references.citation: J Neurosurg. 2011 Jul;115(1):11-7
references.pmid: 21438658
references.citation: Nat Biotechnol. 1999 Apr;17(4):375-8
references.pmid: 10207887
references.citation: Clin Cancer Res. 2013 Jul 15;19(14):3745-54
references.pmid: 23674494
references.citation: Head Neck. 2013 Sep;35(9):1362-70
references.pmid: 22941934
references.citation: Phys Med Biol. 2009 Nov 21;54(22):6991-7008
references.pmid: 19887712
references.citation: Opt Lett. 2012 Mar 1;37(5):948-50
references.pmid: 22378448
references.citation: Anal Biochem. 2009 Jan 15;384(2):254-62
references.pmid: 18938129
references.citation: Nat Rev Cancer. 2012 Apr 19;12(5):323-34
references.pmid: 22513401
references.citation: Breast Cancer Res Treat. 2011 Aug;128(3):679-89
references.pmid: 20821347
references.citation: Curr Opin Chem Biol. 2010 Feb;14(1):71-9
references.pmid: 19879798
references.citation: J Surg Oncol. 2012 Jun 1;105(7):714-8
references.pmid: 21952950
references.citation: Biomaterials. 2012 Mar;33(7):2230-9
references.pmid: 22182749
references.citation: Opt Express. 2009 Jan 19;17(2):860-71
references.pmid: 19158901
references.citation: Cancer Res. 2003 Apr 15;63(8):1727-30
references.pmid: 12702551
references.citation: Ann Surg Oncol. 2001 Jan-Feb;8(1):65-71
references.pmid: 11206227
references.citation: J Biomed Opt. 2008 Nov-Dec;13(6):064042
references.pmid: 19123688
references.citation: Curr Pharm Des. 2012;18(18):2607-21
references.pmid: 22512446