The Effect of VPA Treatment on Radiolabeled DOTATATE Uptake: Differences Observed In Vitro and In Vivo

Autor: Maria Klomp, Leo Hofland, Lilian van den Brink, Peter van Koetsveld, Fadime Dogan, Corrina de Ridder, Debra Stuurman, Marian Clahsen-van Groningen, Marion de Jong, Simone Dalm
Přispěvatelé: Internal Medicine, Radiology & Nuclear Medicine, Urology, Pathology
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmaceutics
Pharmaceutics, 14(1):173. Multidisciplinary Digital Publishing Institute (MDPI)
Pharmaceutics, Vol 14, Iss 173, p 173 (2022)
Pharmaceutics; Volume 14; Issue 1; Pages: 173
ISSN: 1999-4923
Popis: 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.
Databáze: OpenAIRE
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