1707PD - Orthotopic versus subcutaneous NET: tumor tissue characteristics result in different answers when ADC is used to validate early therapy response fo...

Date 10 September 2017
Event ESMO 2017 Congress
Session Basic science
Topics Basic Science
Neuroendocrine Cancers
Presenter Eva Koziolek
Citation Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391
Authors E.J. Koziolek1, J. Albrecht1, S. Exner2, V. Prasad3, C. Grötzinger2, W. Brenner3
  • 1Berlin Experimental Radionuclide Imaging Center (beric), Dkfz Heidelberg, Dktk Partner Site, Charite-Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 2Department Of Hepatology And Gastroenterology And Molecular Cancer Research Center, Universitätsklinik Charité, Campus Virchow Klinikum, 13353 - Berlin/DE
  • 3Department Of Nuclear Medicine, Universitätsklinik Charité, Campus Virchow Klinikum, 13353 - Berlin/DE

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Funding

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

Disclosure

All authors have declared no conflicts of interest.