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FDG may be able to substitute specific hypoxia-targeting agents in PET imaging of tumours, according to a Dutch review, but further evaluation is needed, it cautioned.

FDG may be able to substitute specific hypoxia-targeting agents in PET imaging of tumours, according to a Dutch review, but further evaluation is needed, it cautioned [1].

Identifying tumor-hypoxia can have important implications as radiotherapy may be less effective under these conditions, and dose escalation may be advisable.

Several hypoxia-targeting radiopharmaceuticals have been developed for this purpose, but their availability is poor. Meanwhile, tumor uptake of the more widely available FDG is based on tumor hyperglycolysis, itself driven by hypoxia-inducible factor-1 (HIF-1), largely through tumor hypoxia as the name suggests.

While the authors reported that clinical data on the relationship between FDG uptake and tumour hypoxia are both limited and variable, they noted: "Based on recent data, it appears that HIF-1 expression may also be observed in non-hypoxic tumour regions…. Accordingly, it cannot be excluded that the existence of a correlation or lack of correlation between hypoxia and FDG accumulation is tumour type-dependent."

They elaborated: "In those tumours where HIF-1 activation is mainly hypoxia-driven, the degree of FDG uptake may be a surrogate marker of hypoxia."

Danish researchers disagreed with the potential value of FDG for this purpose. The group assessed the correlation between the hypoxia-targeting agent FAZA and FDG uptake in cell lines [2], reporting that anoxia "strongly stimulated FAZA retention…. Three out of four cell lines displayed similar selectivity of FDG versus glucose."

However, they added: "Problematic for the possible use of FDG in hypoxia imaging is the observation that glucose uptake rate per cell is highly variable."

[1] FDG uptake, a surrogate of tumour hypoxia?
Eur J Nucl Med Mol Imaging 2008; 35: 1544-1549

[2] Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage
Eur J Nucl Med Mol Imaging 2008; Online first