The Effect of VPA Treatment on Radiolabeled DOTATATE Uptake: Differences Observed In Vitro and In Vivo
In: Pharmaceutics, Jg. 14 (2022), Heft 1, S. 173
Online
academicJournal
Zugriff:
Background: To improve peptide receptor radionuclide therapy (PRRT), we aimed to enhance the expression of somatostatin type-2 receptors (SSTR2) in vitro and in vivo, using valproic acid (VPA). Methods: Human NCI-H69 small-cell lung carcinoma cells were treated with VPA, followed by [111In]In-DOTATATE uptake studies, RT-qPCR and immunohistochemistry analysis. Furthermore, NCI-H69 xenografted mice were treated with VPA or vehicle, followed by [177Lu]Lu-DOTATATE injection. Biodistribution studies were performed, and tissues were collected for further analysis. Results: VPA significantly increased SSTR2 expression in vitro. In animals, a statistically significant increased [177Lu]Lu-DOTATATE tumoral uptake was observed when VPA was administered eight hours before [177Lu]Lu-DOTATATE administration, but increased tumor SSTR2 expression levels were lacking. The animals also presented significantly higher [177Lu]Lu-DOTATATE blood levels, as well as an elevated renal tubular damage score. This suggests that the enhanced tumor uptake was presumably a consequence of the increased radiotracer circulation and the induced kidney damage. Conclusions: VPA increases SSTR2 expression in vitro. In vivo, the observed increase in tumoral [177Lu]Lu-DOTATATE uptake is not caused by SSTR2 upregulation, but rather by other mechanisms, e.g., an increased [177Lu]Lu-DOTATATE circulation time and renal toxicity. However, since both drugs are safely used in humans, the potential of VPA to improve PRRT remains open for investigation.
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The Effect of VPA Treatment on Radiolabeled DOTATATE Uptake: Differences Observed In Vitro and In Vivo
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Autor/in / Beteiligte Person: | Klomp, Maria J. ; Hofland, Leo J. ; Lilian van den Brink ; Peter M. van Koetsveld ; Dogan, Fadime ; Corrina M. A. de Ridder ; Stuurman, Debra C. ; Marian C. Clahsen-van Groningen ; Marion de Jong ; Dalm, Simone U. |
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Zeitschrift: | Pharmaceutics, Jg. 14 (2022), Heft 1, S. 173 |
Veröffentlichung: | MDPI AG, 2022 |
Medientyp: | academicJournal |
ISSN: | 1999-4923 (print) |
DOI: | 10.3390/pharmaceutics14010173 |
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