In vivo evaluation of two tissue transglutaminase PET tracers in an orthotopic tumour xenograft model
Background The protein cross-linking enzyme tissue transglutaminase (TG2; EC 2.3.2.13) is associated with the pathogenesis of various diseases, including cancer. Recently, the synthesis and initial evaluation of two high-potential radiolabelled irreversible TG2 inhibitors were reported by us. In the...
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Published in | EJNMMI research Vol. 8; no. 1; pp. 39 - 13 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
25.05.2018
Springer Nature B.V SpringerOpen |
Subjects | |
Online Access | Get full text |
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Summary: | Background
The protein cross-linking enzyme tissue transglutaminase (TG2; EC 2.3.2.13) is associated with the pathogenesis of various diseases, including cancer. Recently, the synthesis and initial evaluation of two high-potential radiolabelled irreversible TG2 inhibitors were reported by us. In the present study, these two compounds were evaluated further in a breast cancer (MDA-MB-231) tumour xenograft model for imaging active tissue transglutaminase in vivo.
Results
The metabolic stability of [
11
C]
1
and [
18
F]
2
in SCID mice was comparable to the previously reported stability in Wistar rats. Quantitative real-time polymerase chain reaction analysis on MDA-MB-231 cells and isolated tumours showed a high level of TG2 expression with very low expression of other transglutaminases. PET imaging showed low tumour uptake of [
11
C]
1
(approx. 0.5 percentage of the injected dose per gram (%ID/g) at 40–60 min p.i.) and with relatively fast washout. Tumour uptake for [
18
F]
2
was steadily increasing over time (approx. 1.7 %ID/g at 40–60 min p.i.). Pretreatment of the animals with the TG2 inhibitor
ERW1041E
resulted in lower tumour activity concentrations, and this inhibitory effect was enhanced using unlabelled
2
.
Conclusions
Whereas the TG2 targeting potential of [
11
C]
1
in this model seems inadequate, targeting of TG2 using [
18
F]
2
was achieved. As such, [
18
F]
2
could be used in future studies to clarify the role of active tissue transglutaminase in disease. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2191-219X 2191-219X |
DOI: | 10.1186/s13550-018-0388-2 |