title: Malignant lipogenesis defined by11C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy.
abstract: OBJECTIVE
  Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions.11C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse11C-acetate PET/CT image metrics in relation to survival.
  
  
  METHODS
  All patients undergoing11C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding11C-acetate uptake intensity (SUVmax) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUVmax× TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis.
  
  
  RESULTS
  A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 ± 4.35 ng/mL. The median follow-up of the study population was 79 ± 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUVmax(r = -0.55, p = 0.01) and nonlinearly with TLA (r = -0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045).
  
  
  CONCLUSIONS
  Malignant11C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death.11C-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit.
authors.affiliation: Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Naresh
authors.initials: N
authors.lastname: Regula
authors.affiliation: Section of Urology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Häggman
authors.affiliation: Section of Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Johansson
authors.affiliation: Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. jens.sorensen@pet.uu.se.|PET Center Research Department, no. 79, 5th floor, Akademiska Sjukhuset, 751 85, Uppsala, Sweden. jens.sorensen@pet.uu.se.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
mesh_terms: D000085:Acetates; D000368:Aged; D002244:Carbon; D006801:Humans; D050155:Lipogenesis; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000000981:diagnostic imaging* / Q000401:mortality*; D000072078:Positron Emission Tomography Computed Tomography; D015995:Prevalence; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality* / Q000601:surgery*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000085:Acetates; D019275:Radiopharmaceuticals; C438206:carbon-11 acetate; D002244:Carbon; D017430:Prostate-Specific Antigen
keywords: 11C-Acetate; Fatty acid synthase; Malignant lipogenesis; Positron emission tomography; Prostate carcinoma; Survival analysis