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Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter–driven AQP1 overexpression
Purpose To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter–driven AQP1 expression. Methods The human telomerase reverse transcriptase (hTERT) promoter–driven AQP1 gene overexpression lentivirus system ( hTERT-AQP1 ) and cytomegalovirus...
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Published in: | European journal of nuclear medicine and molecular imaging 2022-06, Vol.49 (7), p.2310-2322 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose
To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter–driven AQP1 expression.
Methods
The human telomerase reverse transcriptase (hTERT) promoter–driven AQP1 gene overexpression lentivirus system (
hTERT-AQP1
) and cytomegalovirus (CMV) promoter–driven AQP1 gene overexpression lentivirus system (
CMV-AQP1
) were prepared, and transduced into telomerase-positive and -negative cells. The AQP1 expression and DWI signal intensity (SI) change in transduced cells were analyzed. Balb/C nude mice subcutaneous xenograft models derived from lentivirus-transduced telomerase-positive and -negative cells were used to evaluate AQP1 expression and DWI SI change in vivo. We further established another group of subcutaneous xenograft model using pristine telomerase-positive and -negative cells, followed by injecting the lentiviral vectors intratumorally or intravenously, to determine the malignant tumor-targeted imaging of
hTERT-AQP1
.
Results
The
hTERT-AQP1
and
CMV-AQP1
were successfully prepared. After transduction,
hTERT-AQP1
could induce the specific overexpression of AQP1 in telomerase-positive cells. Compared with untransduced cells, all
CMV-AQP1
-pretransduced cells and
hTERT-AQP1
-pretransduced telomerase-positive cells showed decreased SI and increased apparent diffusion coefficient (ADC) in DWI, while
hTERT-AQP1
-pretransduced telomerase-negative cells showed no obvious SI and ADC change. Correspondingly,
hTERT-AQP1
-transduced telomerase-positive tumors and
CMV-AQP1
-transduced telomerase-positive and -negative tumors showed decreased DWI SI and increased ADC, while
hTERT-AQP1
-transduced telomerase-negative tumor had no SI and ADC changes. After intratumoral or intravenous injection,
CMV-AQP1
could upregulate AQP1 expression and induce DWI SI and ADC alteration in both telomerase-positive and -negative tumors, while
hTERT-AQP1
worked in telomerase-positive tumors specifically.
Conclusion
Cancers can be specifically visualized based on the DWI signal alteration which triggered by
hTERT-AQP1
lentivirus system that combined AQP1 gene and hTERT promoter. |
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ISSN: | 1619-7070 1619-7089 1619-7089 |
DOI: | 10.1007/s00259-022-05684-1 |