title: Effect of interferon-alpha treatment on [68Ga-DOTA,Tyr3,Thre8]octreotide uptake in CA20948 tumors: a small-animal PET study.
abstract: In peptide receptor radionuclide therapy of neuroendocrine tumors, improvements have been made by increasing the affinity for receptors and by protecting critical organs (e.g., kidneys). However, tumor parameters involved in radiopeptide uptake are still under investigation. Interferon-α (IFNα) is used as biotherapy for neuroendocrine tumors. Several mechanisms of action are described, but the potential effect of IFNα on tumor uptake of labeled peptide has not been studied in vivo yet.
  
  
  METHODS
  Twenty-six male CA20948 tumor-bearing Lewis rats were imaged before and during IFNα treatment using quantitative small-animal PET with [(68)Ga-DOTA,Tyr(3),Thre(8)]octreotide. Imaging was performed at days 0, 3, and 7. Animals were divided into 3 groups according to the treatment: control (injected daily with saline), half (4 d of IFNα treatment from day 0 to day 3, then saline), and full (7 d of IFNα). A daily dose of IFNα (1.5 mIU) was administered subcutaneously. Quantitative PET results are expressed as percentage injected dose per cm(3) and normalized to baseline (day 0) values. Tumor size was monitored by PET and caliper measurements.
  
  
  RESULTS
  Gross tumor uptake and tumor volumes increased in all groups over the 7-d period. On day 3, mean ± SD ratios to day 0 were 1.2 ± 0.2, 1.3 ± 0.5, and 1.2 ± 0.4, respectively, for control, half, and full groups. On day 7, respective values were 1.1 ± 0.2, 1.3 ± 0.6, and 1.5 ± 0.4. At day 3, a comparison among groups showed no statistically significant difference. At day 7, the full group showed a significantly higher ratio in activity concentration than the control group (P = 0.021). A good correlation was found between tumor volumes assessed by small-animal PET and caliper measurements (R = 0.89, P < 0.0001).
  
  
  CONCLUSIONS
  As expected, over a period of 7 d, both tumor volumes and radiopeptide uptake increased in all animals. However, the activity concentration increased significantly more at day 7 in animals treated for 7 d with IFNα, compared with controls. This is the first, to our knowledge, in vivo indication that IFNα is able to increase tumor uptake of the labeled analog in a small-animal model of neuroendocrine tumors. The mechanisms underlying this effect (flow, vascular permeability, receptor upregulation) remain unknown and need to be further investigated.
authors.affiliation: Molecular Imaging and Experimental Radiotherapy Unit, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Hanin
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pauwels
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Marleen
authors.initials: M
authors.lastname: Melis
authors.forename: Wout
authors.initials: W
authors.lastname: Breeman
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
authors.forename: François
authors.initials: F
authors.lastname: Jamar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D017711:Nonlinear Dynamics; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C513399:gallium Ga 68 dotatate