title: Bone scintigraphy as a new imaging biomarker: the relationship between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases.
abstract: OBJECTIVE
  A computer-aided diagnosis system for bone scintigraphy with a semiquantitative index from the Bone Scan Index (BSI) has been used to quantify the spread of bone metastases. However, few papers have made clear associations among BSI, bone metabolic markers, and prostate-specific antigen (PSA). This retrospective study aimed to examine these relationships in prostate cancer patients with bone metastases.
  
  
  METHODS
  A total of 158 scans from 52 patients (number of median examinations/person 3, range 1-8; median age 71 years, age range 46-86) were included. The intervals between bone scans and blood examinations were 0-16 days (median 0 day). The serum markers of PSA, pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (1-CTP), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were examined. Subjects were divided into 4 groups according to BSI; Group A: 0 to <2, Group B: 2 to <4, Group C: 4 to <8, and Group D: over 8. BSI, which corresponded to the amount of metastatic lesion, was automatically calculated by BONENAVI(®) software (FUJIFILM RI Pharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden).
  
  
  RESULTS
  All bone scans showed high uptake with bone metastases. BSI was correlated significantly with the serum 1-CTP, serum BAP, serum TRACP-5b, logBAP, logTRACP-5b, and logPSA (r = 0.39, 0.66, 0.69, 0.71, 0.62 and 0.41, respectively). BSI did not correlate significantly with the serum PSA. The statistical F value was 11 in the serum 1-CTP, 31 in serum BAP, 29 in logBAP, 19 in serum TRACP-5b, 14 in logTRACP-5b, 3 in serum PSA, and 9 in logPSA by analysis of variance. Comparison by Dunnett's test showed significantly higher values in Group D for all original bone metabolic markers and the logPSA, Group C for the serum BAP, logBAP, serum TRACP-5b, and logTRACP-5b, and Group B for the logTRACP-5b compared with Group A.
  
  
  CONCLUSIONS
  The changes in BSI showed a close relationship with all bone metabolic markers but not with the serum PSA. The BSI is confirmed to reflect the activity and extent of bone metastases, and can be used as an imaging biomarker.
authors.affiliation: Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan, wakabayashi@nmd.m.kanazawa-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakabayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.forename: Anri
authors.initials: A
authors.lastname: Inaki
authors.forename: Junichi
authors.initials: J
authors.lastname: Taki
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000556:secondary; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D011877:Radionuclide Imaging; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen