RT Journal Article SR Electronic T1 Upregulation of Key Molecules for Targeted Imaging and Therapy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1805 OP 1810 DO 10.2967/jnumed.115.165092 VO 57 IS 11 A1 Vincent F. Taelman A1 Piotr Radojewski A1 Nicolas Marincek A1 Anat Ben-Shlomo A1 Andrea Grotzky A1 Cristina I. Olariu A1 Aurel Perren A1 Christoph Stettler A1 Thomas Krause A1 Lorenz P. Meier A1 Renzo Cescato A1 Martin A. Walter YR 2016 UL http://jnm.snmjournals.org/content/57/11/1805.abstract AB Targeted diagnosis and therapy enable precise tumor detection and treatment. Successful examples for precise tumor targeting are diagnostic and therapeutic radioligands. However, patients with tumors expressing low levels of the relevant molecular targets are deemed ineligible for such targeted approaches. Methods: We performed a screen for drugs that upregulate the somatostatin receptor subtype 2 (sstr2). Then, we characterized the effects of these drugs on transcriptional, translational, and functional levels in vitro and in vivo. Results: We identified 9 drugs that act as epigenetic modifiers, including the inhibitor of DNA methyltransferase decitabine as well as the inhibitors of histone deacetylase tacedinaline and romidepsin. In vitro, these drugs upregulated sstr2 on transcriptional, translational, and functional levels in a time- and dose-dependent manner. Thereby, their combinations revealed synergistic effects. In vivo, drug-based sstr2 upregulation improved the tumor-to-background and tumor-to-kidney ratios, which are the key determinants of successful sstr2-targeted imaging and radiopeptide therapy. Conclusion: We present an approach that uses epigenetic modifiers to improve sstr2 targeting in vitro and in vivo. Translation of this method into the clinic may potentially convert patients ineligible for targeted imaging and therapy to eligible candidates.