PET: too much of a good thing? Does the plethora of choices impact on patient management?

Positron emission tomography (PET) is unique in being able to detect nanomolar changes in concentration. This has resulted in an array of radiotracers that target important parameters of neoplastic cell behavior, notably hormone receptors [1] and hypoxia states [2]. Also being studied in clinical trials are “reporter” tracers that track inoculation or activation of a gene of interest [3]. An increasing array of metabolic tracers have been labeled to positron emitters, initially with carbon-11 and increasingly with fluorine-18. These appear largely unlikely to displace F-fluorodeoxyglucose ([F]FDG) as the standard PET imaging tracer, especially for staging [4] and, perhaps more importantly, evaluation of response to therapy [5]. The other determinants of metabolic state— such as radiolabeled acetate, which may be more useful in certain situations because of the route of excretion (e.g., the lack of urinary radioactivity, which permits better delineation of the pelvis) and/or metabolic characteristics (e.g., amino acid rather than carbohydrate metabolism)— will always be complementary to [F]FDG, and therefore one must always consider the incremental value of these radiotracers. The incremental value may contribute to patient management, but it is more likely that the lasting contribution will be to our understanding of cancer biology. The incremental value of tracers other than [F]FDG in the management of a cancer patient will be difficult to assess; [F]FDG PET is part of standard of care in an increasing number of cancer types. Similarly, the incremental value of dual-phase [F]FDG PET studies, as demonstrated so elegantly in the accompanying report by Lyshchik et al. to which this Editorial Commentary relates, is worthy of further investigation. The cost of the incremental value would include, in busy centers, the lost opportunity costs of not carrying out routine standard of care studies in that time period, and one would need to weigh whether, as in this case, the cost of determining a better prognostic subtype of a terrible disease is worth the extra effort. Lyshchik et al. have contributed by demonstrating that not only is deoxyglucose uptake into a cancer cell important, but the retention of the agent is an even better indicator of aggressiveness, perhaps reflective of the anaerobic oxidative need for glucose (as opposed to fatty acid). Studies of this nature can be carried out in the community as well, and will gain in clinical value once better therapeutics are available. Moreover, the unique insights that these studies offer maywell lead to development of more targeted therapies. PET will add immensely to our knowledge and understanding of the cancer phenotype (and, someday, of genotype); these studies therefore need to be done, certainly in academic centers. The ever-expanding body of clinical knowledge available from PET—perhaps the most sensitive whole-body imaging modality for in vivo quantitation —must be employed, nay exploited, to understand the myriad aberrations that constitute this fascinating and deadly condition. The authors have demonstrated convincingly that this can be done even with the most “common” of PET tracers.