Imaging regional variation of cellular proliferation in gliomas using 3′-deoxy-3′-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study

Price, S.J.; Fryer, T.D.; Cleij, M.C.; Dean, A.F.; Joseph, J.; Salvador, R.; Wang, D.D.; Hutchinson, P.J.; Clark, J.C.; Burnet, N.G.; Pickard, J.D.; Aigbirhio, F.I.; Gillard, J.H.

doi:10.1016/j.crad.2008.01.016

« Previous Next »Clinical Radiology
Volume 64, Issue 1 , Pages 52-63, January 2009

Imaging regional variation of cellular proliferation in gliomas using 3′-deoxy-3′-[¹⁸F]fluorothymidine positron-emission tomography: an image-guided biopsy study

S.J. Price
- Academic Neurosurgery Unit, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Guarantor and correspondent: S.J. Price, Academic Neurosurgery Unit, Box 167, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. Tel.: +44 1223 336933; fax: +44 1223 216926.
T.D. Fryer
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
M.C. Cleij
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
A.F. Dean
- Department of Histopathology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
J. Joseph
- Department of Histopathology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
R. Salvador
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Fundacio Sant Joan de Deu, Barcelona, Spain
D.D. Wang
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
P.J. Hutchinson
- Academic Neurosurgery Unit, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
J.C. Clark
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
N.G. Burnet
- University Department of Oncology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
J.D. Pickard
- Academic Neurosurgery Unit, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
F.I. Aigbirhio
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
J.H. Gillard
- Wolfson Brain Imaging Centre, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- University Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Received 30 July 2007; received in revised form 14 January 2008; accepted 24 January 2008.

Aim

To compare regional variations in uptake of 3′-deoxy-3′- [¹⁸F]-fluorothymidine (FLT) images using positron-emission tomography (PET) with measures of cellular proliferation from biopsy specimens obtained by image-guided brain biopsies.

Materials and 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±1.7×10⁻³ml_plasma/min/ml_tissue versus 1.2±0.7×10⁻³ml_plasma/min/ml_tissue; p=0.001). High-grade gliomas showed heterogeneous uptake with a mean K_i of 7.7±4×10⁻³ml_plasma/min/ml_tissue. A threshold K_i^mean of 1.8×10⁻³ 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.

Conclusion

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.