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

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

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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 animationbengal.com administration, but increased tumor SSTR2 camo iphone se case 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.