New horizons in prostate cancer imaging
Section snippets
Transrectal ultrasonography
TRUS is the most commonly used modality for imaging the prostate gland. TRUS enables the accurate determination of prostate size which is useful in determining the “PSA density” (PSA/prostate volume) but its ability to delineate cancer foci is limited. Using high resolution probes, TRUS can demonstrate the zonal anatomy of prostate gland (Fig. 1).
When a cancer is visualized by ultrasound it is usually hypoechoic relative to normal tissue, but small cancer foci are often not demonstrated at all;
Computed tomography (CT)
The contrast resolution of CT is insufficient to distinguish the prostatic anatomy from other adjoining structures (e.g. muscles, bladder wall, etc.) and it is usually impossible to detect cancers within the prostate gland. The ability of CT to depict extracapsular extension is limited except in cases of gross extension. Therefore, CT has a very limited role in tumor detection and staging of prostate cancer [11], [12], [13] (Fig. 3). The main role of CT is in nodal staging and in delineating
Magnetic resonance imaging
MR imaging allows unparalleled anatomic assessment of the prostate with better soft tissue resolution than any other imaging modality. Such detailed anatomic information can be used not only for the detection but also for staging. The highest resolution MR image requires the use of an endorectal coil and phased-array body coil on a magnet with a field strength of at least 1.5 T. Although body coil images can be entirely satisfactory for some indications, images obtained with the endorectal
Dynamic Contrast Enhanced MR imaging
DCE MR imaging evaluates the vascularity in tumors by providing quantitative kinetic parameters reflecting wash-in and wash-out. Vascularity of a neoplastic lesion depends on its blood supply and its capillary permeability. Fast MR scanning sequences combined with the rapid administration of a low molecular weight contrast agent may enable detection of leaky vessels within tumors. Recently, Ocak et al. reported the utility of DCE MR imaging in detecting prostate cancer using 3D fast spin echo
MR spectroscopy
MRS provides information about the cellular metabolites within the prostate gland by displaying the relative concentrations of key chemical constituents such as citrate, choline and creatinine. The normal prostate gland contains low levels of choline and high levels of citrate, whereas prostate cancer lesions demonstrate high levels of choline and decreased levels of citrate. The high choline levels in cancer are related to increased cell turnover. There is an increased amount of soluble free
Diffusion Weighted Imaging (DW-MRI)
DW-MRI evaluates the Brownian motion of free water in tissue. Tissue diffusion is found to be restricted with increased cellularity since the water path is interrupted by cell membranes. Prostate cancer lesions often include tightly packed glandular elements with increased cellularity and diminished extracellular spaces which can be detected with DW-MRI as regions of restricted diffusion. Prostate cancer lesions appear as high signal intensity foci on raw DW-MRI but are low in signal on ADC
Positron emission tomography (PET)
PET is emerging as an important research tool in prostate cancer. In PET, a trace amount of a radioactive compound is administered and the resultant images are 3 dimensional spatial reconstructions of the tracer at the time of imaging. The intensity of the imaging signal is proportional to the amount of tracer and, therefore is potentially quantitative. While the routine clinical spatial resolution is limited (∼4–6 mm), the ability to image physiological processes, such as the rate of glucose
18F-fluorodeoxyglucose
The principle of 18F-fluoro-2-deoxy-2-d-glucose (18F-FDG) imaging is based on Warburg’s observation that the increased metabolic demands of rapidly dividing tumor cells require adenosine triphosphate (ATP) generated by glycolysis [42]. FDG is actively transported into cells and converted into FDG-6-phosphate by hexokinase. Since FDG-6-phosphate is not a substrate for the enzyme responsible for the next step in glycolysis, it is then trapped and accumulates in the cell in proportion to its
11C-acetate
Acetate (AC) is a naturally occurring compound that is converted to acetyl-CoA, a substrate for the TCA cycle, and is incorporated into cholesterol and fatty acids [50]. Even though the exact mechanism of acetate accumulation in tumors is unknown, it is hypothesized that AC becomes incorporated in the membrane lipids of tumor cells [50]. AC is metabolized in various organs and is excreted via the pancreas, enabling imaging of the pelvis without confounding bladder activity. For this reason 1-11
Radiolabeled monoclonal antibodies (mAb)
Radiolabeled monoclonal antibodies directed against specific cell surface antigens have been extensively used in imaging and therapy of cancer [86]. The prostate specific membrane antigen (PSMA) is a good example of such a target. PSMA is a 100-kDa type 2 transmembrane glycoprotein expressed in prostate epithelial cells. PSMA is 94% extracellular and contains short internal and transmembrane domains [87]. Expression is low in normal prostate tissue but increases in both localized and metastatic
Additional promising radiotracers
Additional radiotracers show potential in the evaluation of prostate cancer and warrant further investigation. These include the positron-emitter radioisotopes 18F-fluoride, 11C-methionine, and 11C-tyrosine [96], [97], [98]. The reader is referred to the NCI Molecular Imaging Database (MICAD): http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/micad/home.html. This database currently contains 42 SPECT and 79 PET (as of 05/07/2008) which have been used in humans.
Conclusion
The role of molecular imaging in prostate cancer is continually evolving. New MRI techniques combined with new radiotracers that target not only glucose utilization but also other specific tumor properties such as tumor proliferation, membrane turnover and amino acid transport can potentially stage, re-stage, and monitor treatment in patients with prostate cancer. Molecular imaging does not promise a “magic bullet”, but a new set of tools to understand cancer biology in vivo. It will not
Conflict of interest statement
None declared.
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Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial
2016, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Bone scanning with Tc-99m Methylene Diplosphanate is considered the standard of care for the detection of bone metastasis, but there is a low yield with prostate-specific antigen (PSA) less than 10 ng/mL (16). Newer methods such as diffusion-weighted MR (DWMR) and positron emission tomography (PET) with molecular radiotracers are currently under study for the characterization of therapy recurrence after therapy (17-25). Choline PET radiotracers have also been suggested as a means to individualize postprostatectomy treatment decisions (22); yet, their sensitivity is dependent on PSA level, doubling time, and velocity (22, 26, 27).
Functional and molecular imaging: Applications for diagnosis and staging of localised prostate cancer
2013, Clinical OncologyCitation Excerpt :T2-weighted MRI is the most commonly used component of MP-MRI of the prostate. It provides superior soft tissue contrast and clear delineation of prostatic zonal anatomy [5–7]. Most prostate cancers are low in T2 signal intensity against a background of high T2 signal intensity of the normal peripheral zone, due to loss of normal glandular morphology with prostate cancer (Figure 1).
The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: A systematic review and meta-analysis
2013, European UrologyCitation Excerpt :A most accurate assessment of disease stage is crucial for treatment decisions in staging and restaging settings. However, all the conventional imaging modalities have their limitations [2], and optimizing imaging modalities is a field of intensive research and rapid evolvement. In recent decades, functional imaging as well as techniques unifying anatomic and functional information have been developed and improved [3].
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Gregory Ravizzini and Baris Turkbey contributed equally to this work.