Effect of interferon-alpha on 68Ga-DOTA-Tyr3-Octreotate PET uptake in CA20948 rat tumors

Objectives In Peptide Receptor Radionuclide Therapy (PRRT) of neuroendocrine tumors, improvements have been made by attempting to protect critical organ (e.g. kidneys). Tumor parameters involved in radiopeptide uptake are still under investigation. Interferon alpha (IFN) is used as biotherapy for neuroendocrine tumors. Several mechanisms of action have been described but the specific effect of IFN on tumor uptake of peptide has not been studied in vivo yet.

Methods 26 male CA20948 tumor-bearing Lewis rats where imaged before, during and after 7-days IFN treatment using quantitative MOSAIC animal PET with ⁶⁸Ga-DOTA-Tyr³-octreotate. Imaging was performed at days 0, 3 and 7. Animals were divided in 3 groups according to the treatment : group 1 (control, injected daily with saline); group 2 (half, 4 days IFN treatment from day 0 to day 3, then saline) ; group 3 (full, 7 days IFN treatment). A daily dose of IFN (Intron A, 1.5 MIU) was administered subcutaneously.

Results On day 3, mean±SD %ID/ml ratios to day 0 were 1.2±0.2; 1.2±0.5 and 1.2±0.4 for control, half and full groups, respectively. On day 7, respective values were 1.1±0.2; 1.3±0.6 and 1.5±0.4. At day 7, a statistically significant difference was found between the control and full groups (Student t test, P=0.021). Good correlation between imaging assessment of tumor volume (manual VOI) and caliper measurements was found (r=0.89; P<0.0001).

Conclusions As expected, over a period of 7 days, both tumor volumes and radiopeptide uptake increased in all animals. However, a more pronounced increase in uptake was noted in IFN-treated rats as compared to controls, suggesting possible upregulation of somatostatin receptors expression on short-term therapy with IFN.