Upregulation of Key Molecules for Targeted Imaging and Therapy.

Taelman, Vincent; Radojewski, Piotr; Marincek, Nicolas; Ben-Shlomo, Anat; Grotzky, Andrea; Olariu, Cristina I; Perren, Aurel; Stettler, Christoph; Krause, Thomas Michael; Meier, Lorenz; Cescato, Renzo; Walter, Martin A. (2016). Upregulation of Key Molecules for Targeted Imaging and Therapy. Journal of nuclear medicine, 57(11), pp. 1805-1810. Society of Nuclear Medicine 10.2967/jnumed.115.165092

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Klinische Radiopharmazie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Klinische Radiopharmazie

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Taelman, Vincent; Radojewski, Piotr; Grotzky, Andrea; Perren, Aurel; Stettler, Christoph; Krause, Thomas Michael; Meier, Lorenz; Cescato, Renzo and Walter, Martin Alexander

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0161-5505

Publisher:

Society of Nuclear Medicine

Language:

English

Submitter:

Aurel Perren

Date Deposited:

21 Dec 2016 14:06

Last Modified:

24 Jan 2017 16:56

Publisher DOI:

10.2967/jnumed.115.165092

PubMed ID:

27363833

Uncontrolled Keywords:

DOTATATE; DOTATOC; PRRT; molecular imaging; neuroendocrine tumors

BORIS DOI:

10.7892/boris.91972

URI:

https://boris.unibe.ch/id/eprint/91972

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