Early diagnosis and therapy of prostate cancer continue to be challenging. By means of advanced computational genome data-mining and modeling methods, Pospisil et al. have identified prostatic acid phosphatase (PAP) as a candidate for Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), an enzyme-dependent, tumor-specific approach that aims to precipitate water-soluble radioactive prodrugs within the extracellular space of solid tumors. The authors show that the prodrug 2-(2′-phosphoryloxyphenyl)-6-[¹²⁵I/¹²⁷I]iodo-4-(3H)-quinazolinone ([¹²⁵IQ_2-P/¹²⁷IQ_2-P]) favorably docks in silico into the X-raystructure of PAP. In vitro studies show that incubation of the iodinated,nonfluorescent, water-soluble prodrug with PAP leads to rapid hydrolysis and formation of the iodinated, fluorescent, water-insoluble drug 2-(2′-hydroxyphenyl)-6-[¹²⁵I/¹²⁷I]iodo-4-(3H)-quinazolinone ([¹²⁵IQ_2-OH/¹²⁷IQ_2-OH]).Similarly, the incubation of ¹²⁷IQ_2-P with human LNCaP, PC-3, and 22Rv1 prostate tumor cells results in formation of large fluorescent ¹²⁷IQ_2-OH crystals, whereas no hydrolysis is seen in the presence of normal human cells. Autoradiography of tumor cells that had been incubated with ¹²⁵IQ_2-P demonstrates accumulation of radioactive grains (¹²⁵IQ_2-OH) around the cells. When the prodrug is labeled with a suitable radioiodine isotope, the EMCIT approach has potential for detection (¹²³I-SPECT, ¹²⁴I-PET) and treatment (¹³¹I) of solid prostate tumors. For details, see the article by Pospisil et al. on page 2197 of this issue.