Tumor uptake of ⁶⁸Ga-DOTA-Tyr³-octreotate: animal PET studies of tumor flow and acute somatostatin receptor modulation in the CA20948 rat model

Abstract 

Introduction

Factors determining the in vivo uptake of radiolabeled somatostatin analogs by neuroendocrine tumors are poorly known. The aim is to evaluate in vivo tumor perfusion and regulation of somatostatin receptors (sstr) following acute exposure to octreotide, in an animal model of neuroendocrine tumor.

Methods

H₂¹⁵O flow studies were performed in 8 CA20948 tumor-bearing rats and another 36 rats underwent three [⁶⁸Ga]-DOTA-Tyr³-octreotate imaging sessions at 24-h intervals. After baseline (Day 0) imaging, scanning was repeated on Day 1 after octreotide injection (175 μg/kg), with a variable delay: no injection (controls, n=7), coinjection (n=6), and octreotide injection 20 min (n=7), 2 h (n=8) and 4 h (n=8) before imaging. Repeat images without octreotide was performed at Day 2 followed by sacrifice and tumor counting.

Results

H₂¹⁵O studies failed to measure quantitative tumor perfusion in this model. On Day 1, ratio of tumor uptake to Day 0 was 1.2±0.3 in controls; 0.6±0.2 in the coinjection group; 0.9±0.2, 1.1±0.1 and 1.2±0.2 in the other groups, respectively. Uptake in the coinjection group showed a statistically significant reduction of tumor uptake (P<.0001). All groups showed increased uptake on Day 2, without statistical differences between groups. In vivo tumor counts showed good correlation with ex vivo countings (R²=0.946).

Conclusion

Acute exposure to unlabeled octreotide in this neuroendocrine tumor model results in a rapid recycling or resynthesis of sstr. Positron emission tomography (PET) allowed to reliably assess quantitative uptake of [⁶⁸Ga]-DOTA-Tyr³-octreotate over time in the same animal, but failed in this model to measure tumor perfusion.

Keywords: Gallium 68, Octreotide, PRRT, DOTA-Tyr3-octreotate, CA20948 tumor