title: Assessment of PET tracer uptake in hormone-independent and hormone-dependent xenograft prostate cancer mouse models.
abstract: The pharmacokinetics of (18)F-fluorodeoxythymidine (FLT), (18)F-FDG, (11)C-choline, and (18)F-fluoroethylcholine (FEC) in 2 hormone-independent (PC-3, DU145) and 2 hormone-dependent (CWR22, PAC120) prostate cancer xenograft mouse models were evaluated by PET and compared by immunohistochemistry. Further investigation was performed to determine whether PET can detect early changes in tumor metabolism after androgen ablation therapy through surgical castration.
  
  
  METHODS
  PET was performed on 4 consecutive days. In addition, the CWR22 and PAC120 tumor models were surgically castrated after the baseline measurement and imaged again after castration. The tracer uptake was analyzed using time-activity curves, percentage injected dose per volume (%ID/cm(3)), and tumor-to-muscle ratio (T/M).
  
  
  RESULTS
  Regarding the hormone-independent prostate tumor models, (18)F-FLT showed the best T/M and highest %ID/cm(3) in PC-3 (2.97 ± 0.63 %ID/cm(3)) and DU145 (2.06 ± 0.75 %ID/cm(3)) tumors. (18)F-FDG seemed to be the tracer of choice for delineation of the PC-3 tumors but not for the DU145 tumors. Using (11)C-choline (PC-3: 1.33 ± 0.29 %ID/cm(3), DU145: 1.60 ± 0.27 %ID/cm(3)) and (18)F-FEC, we did not find any significant uptake in the tumors, compared with muscle tissue. Regarding the hormone-dependent prostate tumor models, the CWR22 model showed a highly significant (P < 0.01) decrease in tumor (18)F-FDG uptake from 4.11 ± 1.29 %ID/cm(3) to 2.19 ± 1.45 %ID/cm(3) after androgen ablation therapy. However, the (18)F-FLT, (11)C-choline, or (18)F-FEC tracers did not provide sufficient uptake or reliable information about therapy response in CWR22 tumors. The PAC120 model showed a significant increase in (18)F-FLT tumor uptake (P = 0.015) after androgen ablation therapy. The accumulation of (18)F-FEC (before: 2.32 ± 1.01 %ID/cm(3), after: 1.36 ± 0.39 %ID/cm(3)) was found to be the next highest after (18)F-FDG (before: 2.45 ± 0.93 %ID/cm(3), after: 2.18 ± 0.65 %ID/cm(3)) in PAC120 tumors before castration and is better suited for monitoring therapy response.
  
  
  CONCLUSIONS
  This comprehensive study in 2 hormone-dependent and 2 hormone-independent prostate tumor mouse models shows that (18)F-FLT and (18)F-FDG are the most appropriate tracers for delineation of PC-3, DU145 (except (18)F-FDG), and CWR22 tumors, but not for PAC120 tumors. (18)F-FEC and (11)C-choline, in particular, revealed insufficient T/M ratio in the prostate tumor models. The results may indicate that radiolabeled choline and choline derivatives compete with a high concentration of the precursor dimethylaminoethanol, resulting in reduced uptake in small-rodent tumor models, a hypothesis that is currently under investigation in our laboratory.
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Eberhard Karls University, Tübingen, Germany.
authors.forename: Damaris
authors.initials: D
authors.lastname: Kukuk
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.forename: Olivier
authors.initials: O
authors.lastname: Raguin
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.forename: Martin S
authors.initials: MS
authors.lastname: Judenhofer
authors.forename: Carsten
authors.initials: C
authors.lastname: Calaminus
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Honndorf
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Olivier
authors.initials: O
authors.lastname: Duchamp
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Machulla
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002794:Choline / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009919:Orchiectomy; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014183:Transplantation, Heterologous
chemical_list: D002250:Carbon Radioisotopes; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C448902:fluoroethylcholine; D002794:Choline; C002854:alovudine