(11)C-acetate PET imaging in prostate cancer.

The patient population with a rising PSA following definitive local therapy represents the second largest group of prostate cancer patients [1]. These patients are characterized by a rising marker following definitive local therapy with either surgery or radiation, and by definition have no evidence of disease on standard imaging studies [2]. By some estimates, approximately 50,000 men in the USA enter this clinical state each year [3]. Although some reports suggest that the median amount of time that a patient will spend in this clinical state before developing metastatic disease is 8 years [4], in actuality these patients represent a wide spectrum of clinical risk. Some have rapidly progressive micrometastatic disease and are at high risk for developing metastases; others experience locally persistent disease or an otherwise indolent clinical course. Distinguishing between these patients plays a critical role in selecting appropriate treatment. A patient with aggressive micrometastatic disease is a candidate for systemic treatments. On the other hand, patients who have no systemic disease and an exclusively local residual tumor may be cured with local salvage strategies [5, 6]. This rising-PSA population is regarded by many clinical investigators as the most challenging in terms of testing and developing new therapies for prostate cancer care. These patients experience a highly variable clinical course, and often have no radiographic findings, no symptoms, and no tissue-based assessments by which treatment effects can be evaluated. To address these limitations, consensus guidelines have been published to define a framework for conducting trials, but even these guidelines recommend that investigators be cautious about testing drugs early in such patients, given the methodological challenges [7]. Paradoxically, though, radiologists are attracted to trials involving this clinical state because it is literally defined by the inadequacies of present imaging modalities for prostate cancer. Bone and CT scans are insensitive in detecting osseous metastases. For locally recurrent disease, magnetic resonance imaging (MRI), with a specific acquisition protocol that focuses on the pelvis, can detect abnormalities in the prostate bed, but again, distinguishing postoperative changes from active tumor is challenging, and many of these sites are in areas that are not routinely biopsied based on standard algorithms. Positron emission tomography (PET) has been posited by some as a solution to these limitations. Rather than examining the derivative effects on bone, it can demonstrate the biology of the tumor itself; it also offers the potential to image sites in bone and soft tissue simultaneously and to survey the entire body rapidly. It could possibly distinguish fibrosis from active cancer in the prostate bed in a postsurgical patient, a disease-free residual prostate from one containing active cancer in a postradiation therapy (post-RT) patient, and early bone metastases from nonmalignant injuries and inflammatory osseous lesions. A study by Dr. Albrecht and colleagues examined the use of PETwith C-acetate, a tracer of fatty acid synthesis. Although the mechanism of tracer uptake in cancers is not wholly clear, it has been posited that metabolic activity in the tumor occurs in a low-oxygen microenvironment, in This editorial commentary refers to the article http://dx.doi.org/10.1007/s00259-006-0163-x.