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

Academic Neurosurgery Unit, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Clinical Radiology (Impact Factor: 1.76). 01/2009; 64(1):52-63. DOI: 10.1016/j.crad.2008.01.016
Source: PubMed


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.
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.
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.
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.

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    • "18F-fluorothymidine (FLT), which is known to be actively taken up into dividing cells, has an excellent contrast-to-background ratio[30], and studies measuring FLT uptake have shown that it associates well with tissue markers of proliferation. However, even if areas of abnormality are larger than those visualized on MRI when using image-guided biopsies, it has also been shown that FLT could underestimate the extent of the tumors in half of the cases[31]. "
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