Castration-resistant prostate cancer bone metastasis response measured by 18F-fluoride PET after treatment with dasatinib and correlation with progression-free survival: results from American College of Radiology Imaging Network 6687

J Nucl Med. 2015 Mar;56(3):354-60. doi: 10.2967/jnumed.114.146936. Epub 2015 Jan 29.


(18)F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone.

Methods: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent (18)F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in (18)F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between (18)F-fluoride incorporation in tumor and normal bone, (18)F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover.

Results: Eighteen participants enrolled, and 17 underwent interpretable baseline (18)F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential (18)F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in (18)F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47).

Conclusion: This trial provides evidence of the ability (18)F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.

Keywords: 18F-fluoride PET; bone metastases; dasatinib; metastatic castration-resistant prostate cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / secondary
  • Bone and Bones / pathology
  • Dasatinib
  • Disease-Free Survival
  • Fluorine Radioisotopes*
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Positron-Emission Tomography*
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use*
  • Receptors, Androgen / metabolism
  • Thiazoles / therapeutic use*
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Fluorine Radioisotopes
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Receptors, Androgen
  • Thiazoles
  • Dasatinib