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2017 ; 8
(34
): 57231-57245
Nephropedia Template TP
gab.com Text
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English Wikipedia
Assessment of near-infrared fluorophores to study the biodistribution and tumor
targeting of an IL13 receptor ?2 antibody by fluorescence molecular tomography
#MMPMID28915667
Gupta P
; Wentland JA
; Leal M
; Ma D
; Roach R
; Esparza A
; King L
; Spilker ME
; Bagi C
; Winkelmann CT
; Giddabasappa A
Oncotarget
2017[Aug]; 8
(34
): 57231-57245
PMID28915667
show ga
Non-invasive imaging using radiolabels is a common technique used to study the
biodistribution of biologics. Due to the limited shelf-life of radiolabels and
the requirements of specialized labs, non-invasive optical imaging is an
attractive alternative for preclinical studies. Previously, we demonstrated the
utility of fluorescence molecular tomography (FMT) an optical imaging modality in
evaluating the biodistribution of antibody-drug conjugates. As FMT is a
relatively new technology, few fluorophores have been validated for in vivo
imaging. The goal of this study was to characterize and determine the utility of
near-infrared (NIR) fluorophores for biodistribution studies using interleukin-13
receptor subunit alpha-2 antibody (IL13R?2-Ab). Eight fluorophores (ex/em:
630/800 nm) with an N-hydroxysuccinimide (NHS) linker were evaluated for Ab
conjugation. The resulting antibody-fluorophore (Ab-F) conjugates were evaluated
in vitro for degree of conjugation, stability and target-binding, followed by in
vivo/ex vivo FMT imaging to determine biodistribution in a xenograft model. The
Ab-F conjugates (except Ab-DyLight800) showed good in vitro stability and antigen
binding. All Ab-F conjugates (except for Ab-BOD630) resulted in a quantifiable
signal in vivo and had similar biodistribution profiles, with peak tumor
accumulation between 6 and 24 h post-injection. In vivo/ex vivo FMT imaging
showed 17-34% ID/g Ab uptake by the tumor at 96 h. Overall, this is the first
study to characterize the biodistribution of an Ab using eight NIR fluorophores.
Our results show that 3-dimensional optical imaging is a valuable technology to
understand biodistribution and targeting, but a careful selection of the
fluorophore for each Ab is warranted.