Shadi A. Esfahani MD, MPH, Presenter: Nothing to Disclose

Pedram Heidari MD, Abstract Co-Author: Nothing to Disclose

Nazife S. Turker, Abstract Co-Author: Nothing to Disclose

Umar Mahmood MD, PhD, Abstract Co-Author: Research Grant, Sabik Medical Inc

We assessed the ability of a novel phosphatase activatable agent, selective for Prostate Specific Acid Phosphatase (PAP) for the detection of prostate cancer (PCa). Cleavage by PAP results in increased fluorescence and radioactive signal due to a local phase change at sites overexpressing the enzyme.

In vitro, 3 PCa cell lines (AT3-B, LNCaP and PC-3) were incubated with 0.1 mg/ml of the soluble probe 2-(2’-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (127IQ2-P). Dephosphorylation and extracellular precipitation of the probe was assessed using confocal microscope over 24 hrs. PC-3 cells were implanted in 16 nu/nu mice. Epifluorescence imaging (excitation/emission, 480/530 nm) was performed 1 and 24 hrs after IV injection of the probe with concentrations of 1 and 0.1 mg/ml (n=8 each). Signal intensity in xenografts, and tumor to background ratio (TBR) were measured. Biodistribution and histopathologic studies were performed at each time point.

In vitro incubation of the probe with all PAP-overexpressing cell lines resulted in phase transition and formation of the corresponding water-insoluble compound in the extracellular space over 24 hrs. In vivo, rapid hydrolysis of the probe within the tumor resulted in peak fluorescence signal intensity and high TBR 1 hr post injection, with non-significant difference between the mean TBR using 2 different probe concentrations [(TBR with 0.1mg/ml: 4.12±0.2 at 1hr vs. 2.45±0.12 at 24 hrs) and (TBR 1mg/ml: 3.44±0.12 in 1 hr, vs. 2.42±0.08 in 24 hrs)]. Biodistribution studies showed rapid probe accumulation in xenografts, fast probe clearance from the background tissues and its excretion through the kidneys.

Rapid activation, multimodal detection, and high TBR suggest that this phase transition PAP-activatable probe is promising for imaging PCa. This multimodal probe may be employed in early detection of primary and metastatic prostate cancers, treatment response evaluations, and selective image-guided interventions.

The phase-transition activatable probe has the potential in early detection and treatment response evaluation of prostate cancer by targeting the diagnostic marker prostate specific acid phosphatase.

Esfahani, S, Heidari, P, Turker, N, Mahmood, U, A Novel Phase Transition-activatable Multi-Modal Imaging Agent for Prostate Cancer.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14016494.html