Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Basic science

5280 - Orthotopic versus subcutaneous NET: tumor tissue characteristics result in different answers when ADC is used to validate early therapy response following Peptide Receptor Radionuclide Therapy (PRRT)


10 Sep 2017


Basic science


Cancer Biology;  Neuroendocrine Tumours


Eva Koziolek


Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391


E.J. Koziolek1, J. Albrecht1, S. Exner2, V. Prasad3, C. Grötzinger2, W. Brenner3

Author affiliations

  • 1 Berlin Experimental Radionuclide Imaging Center (beric), Dkfz Heidelberg, Dktk Partner Site, Charite-Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 2 Department Of Hepatology And Gastroenterology And Molecular Cancer Research Center, Universitätsklinik Charité, Campus Virchow Klinikum, 13353 - Berlin/DE
  • 3 Department Of Nuclear Medicine, Universitätsklinik Charité, Campus Virchow Klinikum, 13353 - Berlin/DE


Abstract 5280


Preclinical studies in oncology are often performed in subcutaneous tumor models, where therapy success is validated by measuring changes in tumor size. We first characterized subcutaneous (sc) versus orthotopically grown neuroendocrine tumors of the pancreas (NET) with high versus low somatostatin receptor subtype 2 (SSTR2) by multimodal imaging and validated the apparent diffusion coefficient (ADC) as a potential biomarker for early therapy response following SSTR2-specific PRRT.


NET cells (native, SSTR2-transfected BON) were inoculated sc or orthotopically (n = 20) in SCID mice. Tumor characteristics were monitored using a small animal nanoScanPET/MRI: (T1/T2w anatomy, diffusion-weighted imaging, dynamic contrast-enhanced MRI, angiography; PET: Ga-68-DOTATOC, F-18-FDG. PRRT: ADC values and tumor growth were measured to monitor PRRT effects following Lu-177-DOTATOC injection.


Native BON tumors showed different morphologic and metabolic patterns between sc and orthotopic tumors. Sc BON/SSTR2 tumors were similar to native sc BON tumors, while orthotopic BON/SSTR2 tumors were strongly growth delayed and developed necrosis at an early stage compared to native orthotopic BON tumors. Accept of the orthotopic BON/SSTR2 tumors, small tumors appeared solid with high FDG uptake. During tumor growth necrosis increased and FDG decreased. Perfusion was increased in orthotopic versus sc tumors (ktrans = 0,49 min−1 and 0,31 min−1). Interestingly, Lu-177-DOTATOC uptake was ∼4 times higher in sc than in orthotopic BON/SSTR2 tumors. While the ADC reflected the early effects of PRRT (first 9 days) precisely in orthotopic tumors, therapy response could not be validated by ADC in sc tumors due to initial high liquid content in the tissue.


Successful therapy validation presupposes precise knowledge about the used xenograft und the tumor morphology in order to allow correct interpretation of therapeutic effects. In particular, the orthotopic SSTR2- tumors do reflect the physiological situation better than sc tumors and allow to use the ADC as a potential biomarker for early validation of PRRT effects.

Clinical trial identification

Legal entity responsible for the study

DKTK German Cancer Konsortium/DKFZ German Cancer Research Center


DKTK - German Cancer Konsortium, German Cancer Center (DKFZ)


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.