In vitro and in vivo studies demonstrate the ability of the analog of
18F fluorthanatrace (18F-FTT),
125I-KX1, to provide a measurement of poly (adenosine
diphosphate–ribose) polymerase-1 (PARP-1) expression levels in
tumor cells or a solid tumor. In vitro cell uptake study was performed
using MEF PARP-1 KO−/−, MEF PAR2 KO −/−, and
MEF wild-type cell. The cells were incubated with 125I-KX1,
and the uptake was abrogated by the knockout of PARP-1 activity, shown
in the top left. 125I-KX1 uptake was not decreased in the
wild-type and the PARP-2 knockout cell line, showing the specificity of
the 18F-FTT uptake to PARP-1 expression. PARP-1 activity was
measured in three different cell lines, HCC1937 (BRCA
mutation), MD-MBA-231 (triple negative), and MCF (ER positive). In vivo
studies using xenografts implanted with three different cell lines
revealed that the uptake of 125I-KX1, as shown in tumor to
muscle ratio (TMR), paralleled the expression levels of PARP-1 in these
cells. AU = arbitrary unit, BRCA = breast cancer gene,
ER = estrogen receptor, KO = knockout, MEF = mouse embryonic
fibroblast.