Preclinical Imaging of Prostate Cancer

Prostate cancer remains a major cause of mortality and morbidity, affecting millions of men, with a large percentage expected to develop the disease as they reach advanced ages. Treatment and management advances have been dramatic over the past 50 years or so, and one aspect of these improvements is reflected in the multiple advances in diagnostic imaging techniques. Much attention has been focused on molecular imaging techniques that offer high sensitivity and specificity and can now more accurately assess disease status and detect recurrence earlier. During development of molecular imaging probes, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) must be evaluated in preclinical models of the disease. If such agents are to be translated to the clinic, where patients undergoing these imaging modalities are injected with a molecular imaging probe, these agents must first be approved by the FDA and other regulatory agencies prior to their adoption in clinical practice. Scientists have worked assiduously to develop preclinical models of prostate cancer that are relevant to the human disease to enable testing of these probes and related targeted drugs. Challenges in developing reproducible and robust models of human disease in animals are beset with practical issues such as the lack of natural occurrence of prostate cancer in mature male animals, the difficulty of initiating disease in immune-competent animals and the sheer size differences between humans and conveniently smaller animals such as rodents. Thus, compromises in what is ideal and what can be achieved have had to be made. The workhorse of preclinical animal models has been, and remains, the investigation of human xenograft tumor models in athymic immunocompromised mice. Later models have used other immunocompromised models as they have been found and developed, including the use of directly derived patient tumor tissues, completely immunocompromised mice, orthotopic methods for inducing prostate cancer within the mouse prostate itself and metastatic models of advanced disease. These models have been developed in close parallel with advances in imaging agent chemistries, radionuclide developments, computer electronics advances, radiometric dosimetry, biotechnologies, organoid technologies, advances in in vitro diagnostics, and overall deeper understandings of disease initiation, development, immunology, and genetics. The combination of molecular models of prostatic disease with radiometric-based studies in small animals will always remain spatially limited due to the inherent resolution sensitivity limits of PET and SPECT decay processes, fundamentally set at around a 0.5 cm resolution limit. Nevertheless, it is central to researcher's efforts and to successful clinical translation that the best animal models are adopted, accepted, and scientifically verified as part of this truly interdisciplinary approach to addressing this important disease.