Measuring oncogenic signaling pathways in cancer with PET: an emerging paradigm from studies in castration-resistant...

As parallel advances in cancer biology and drug development continue to elevate the role of targeted therapies in oncology, the need for imaging biomarkers that systematically measure the biology associated with therapeutic intervention has become more urgent. Although the molecular imaging community has a commitment to develop technologies to this end, few investigational radiotracers directly measure the biology of common oncogenic signaling pathways often addressed by targeted therapies. Visible progress has been achieved with a handful of radiotracers rationally designed to intercalate the pathobiology of prostate cancer, a molecularly heterogeneous disease nevertheless broadly defined by a fairly small repertoire of recurrent oncogenic lesions.

That variable treatment responses or emergent resistance phenotypes are often documented in humans argues strongly for diagnostic technologies that can be realistically applied posttherapy to capture the dynamic patterns of disease response. The purpose of this review is to describe a collection of radiotracers developed to measure the pathobiology of prostate cancer for improved treatment monitoring, placing particular emphasis on the biologic rationale for their preparation. A chronologic description of radiotracer development programs is outlined, primarily to stress how an ongoing dialectic between earlier and more contemporary imaging technologies has accelerated discovery.