Dynamic Ga-68 DOTATOC PET for segregation of tumor perfusion from somatostatin receptor expression on neuroendocrine tumor (NET)

Objectives: To generate quantitative parameters from dynamic Ga-68 DOTATOC PET (PET) as new markers for tumor perfusion and somatostatin receptor expression on gastroenteropancreatic NET.

Methods: PET was performed in 8 patients (pts) Images were acquired in list mode for 15 minutes after i.v. bolus injection. 63 regions of interests (spleen/adrenals, n=21; normal liver tissue, n=8; primary tumor/metastases (mets); n=34) were evaluated to generate k1, k2, k3, k4 and the fractional blood volume (fbv) using a reversable two compartment model.

Results: Mets in pts with proliferation rate (Ki67) 5-20% showed (n=12) significant higher k1, k2, k3, k4 (all p<0.01) compared to pts with lower Ki67 (<5%) (n=22) but significantly lower fbv (p<0.05). In liver (not receptor-specific uptake), k2 was signficantly higher (p<0.05) than in mets (median, 0.50 vs 0.23). SUVmax in mets showed significant correlations with k1 (rho, 0.37; p<0.001) und fbv (rho, 0.51; p<0.01) but not with k3. SUVmax in spleen/adrenal glands (receptor-specific uptake) correlated significantly with k3 (rho, 0.51; p<0.05).

Conclusions: These preliminary results, within its limitations (low pts number) suggests that dynamic Ga-68 DOTATOC PET enables segregation of tumor perfusion (fbv) from receptor specific binding (k1) in mets. Both parameters, fbv and k1, are primarily correlated to SUVmax in mets. The internalization of receptor ligand (Ga-68 DOTATOC) complexes (k3) appears to be mainly responsible for specific uptake in spleen and adrenal glands, while in normal liver a significantly higher washout of the ligand (k2) was observed which is in line with non-specific peptide uptake due to peptide metabolism in the liver. Moreover, mets in pts with higher Ki67 showed higher receptor ligand dynamics as denoted by higher k1-4 values.