title: Imaging regional variation of cellular proliferation in gliomas using 3'-deoxy-3'-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study.
abstract: OBJECTIVE
  To compare regional variations in uptake of 3'-deoxy-3'- [(18)F]-fluorothymidine (FLT) images using positron-emission tomography (PET) with measures of cellular proliferation from biopsy specimens obtained by image-guided brain biopsies.
  
  
  METHODS
  Fourteen patients with a supratentorial glioma that required an image-guided brain biopsy were imaged preoperatively with dynamic PET after the administration of FLT. Maps of FLT irreversible uptake rate (K(i)) and standardized uptake value (SUV) were calculated. These maps were co-registered to a gadolinium-enhanced T1-weighted spoiled gradient echo (SPGR) sequence that was used for biopsy guidance, and the mean and maximum K(i) and SUV determined for each biopsy site. These values were correlated with the MIB-1 labelling index (a tissue marker of proliferation) from these biopsy sites.
  
  
  RESULTS
  A total of 57 biopsy sites were studied. Although all measures correlated with MIB-1 labelling index, K(i)(max) provided the best correlation (Pearson coefficient, r=0.68; p<0.001). In low-grade gliomas the K(i)(mean) (+/-SD) was significantly higher than in normal tissue (3.3+/-1.7x10(-3)ml(plasma)/min/ml(tissue) versus 1.2+/-0.7x10(-3)ml(plasma)/min/ml(tissue); p=0.001). High-grade gliomas showed heterogeneous uptake with a mean K(i) of 7.7+/-4x10(-3)ml(plasma)/min/ml(tissue). A threshold K(i)(mean) of 1.8x10(-3) differentiates between normal tissue and tumour (sensitivity 84%, specificity 88%); however, the latter threshold underestimated the extent of tumour in half the cases. SUV closely agreed with K(i) measurements.
  
  
  CONCLUSIONS
  FLT PET is a useful marker of cellular proliferation that correlates with regional variation in cellular proliferation; however, it is unable to identify the margin of gliomas.
authors.affiliation: Academic Neurosurgery Unit, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. sjp58@cam.ac.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Price
authors.forename: T D
authors.initials: TD
authors.lastname: Fryer
authors.forename: M C
authors.initials: MC
authors.lastname: Cleij
authors.forename: A F
authors.initials: AF
authors.lastname: Dean
authors.forename: J
authors.initials: J
authors.lastname: Joseph
authors.forename: R
authors.initials: R
authors.lastname: Salvador
authors.forename: D D
authors.initials: DD
authors.lastname: Wang
authors.forename: P J
authors.initials: PJ
authors.lastname: Hutchinson
authors.forename: J C
authors.initials: JC
authors.lastname: Clark
authors.forename: N G
authors.initials: NG
authors.lastname: Burnet
authors.forename: J D
authors.initials: JD
authors.lastname: Pickard
authors.forename: F I
authors.initials: FI
authors.lastname: Aigbirhio
authors.forename: J H
authors.initials: JH
authors.lastname: Gillard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods; D001931:Brain Mapping / Q000379:methods; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D015642:Radiology, Interventional / Q000379:methods; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine