New horizons in prostate cancer imaging

https://doi.org/10.1016/j.ejrad.2008.09.019Get rights and content

Abstract

Prostate cancer is the most common non-cutaneous malignancy among American men. Imaging has recently become more important in detection of prostate cancer since screening techniques such as digital rectal examination (DRE), prostate specific and transrectal ultrasound guided biopsy have considerable limitations in diagnosis and localization of prostate cancer. In this manuscript, we reviewed conventional, functional and targeted imaging modalities used in diagnosis and local staging of prostate cancer with exquisite images.

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.

References (98)

  • M.J. Manyak et al.

    Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer

    Urology

    (1999)
  • K.J. Langen et al.

    3-[123I]Iodo-[alpha]-methyl-l-tyrosine: uptake mechanisms and clinical applications

    Nucl Med Biol

    (2002)
  • A. Jemal et al.

    Cancer Statistics, 2007

    CA Cancer J Clin

    (2007)
  • M.C. Wang et al.

    Purification of a human prostate specific antigen

    Invest Urol

    (1979)
  • H.B. Carter et al.

    Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease

    J Am Med Assoc

    (1992)
  • M.B. Gretzer et al.

    PSA markers in prostate cancer detection

    Urol Clin North Am

    (2003)
  • H. Hricak et al.

    Imaging prostate cancer: a multidisciplinary perspective

    Radiology

    (2007)
  • M. Mitterberger et al.

    The value of three-dimensional transrectal ultrasonography in staging prostate cancer

    BJU Int

    (2007)
  • K. Stamatiou et al.

    Impact of additional sampling in the TRUS-guided biopsy for the diagnosis of prostate cancer

    Urol Int

    (2007)
  • F. Cornud et al.

    Endorectal color Doppler sonography and endorectal MR imaging features of nonpalpable prostate cancer: correlation with radical prostatectomy findings

    Am J Roentgenol

    (2000)
  • K. Taymoorian et al.

    Transrectal broadband-Doppler sonography with intravenous contrast medium administration for prostate imaging and biopsy in men with an elevated PSA value and previous negative biopsies

    Anticancer Res

    (2007)
  • J. Rorvik et al.

    Inability of refined CT to assess local extent of prostatic-cancer

    Acta Radiol

    (1993)
  • J.F. Platt et al.

    The accuracy of CT in the staging of carcinoma of the prostate

    Am J Roentgenol

    (1987)
  • B. Tombal et al.

    Magnetic resonance imaging of the axial skeleton enables objective measurement of tumor response on prostate cancer bone metastases

    Prostate

    (2005)
  • O. Akin et al.

    Transition zone prostate cancers: features, detection, localization, and staging at endorectal MR imaging

    Radiology

    (2006)
  • L. Wang et al.

    Prostate cancer: incremental value of endorectal MR imaging findings for prediction of extracapsular extension

    Radiology

    (2004)
  • F.G. Claus et al.

    Pretreatment evaluation of prostate cancer: role of MR imaging and H-1 MR spectroscopy

    Radiographics

    (2004)
  • E. Sala et al.

    Endorectal MR imaging in the evaluation of seminal vesicle invasion: diagnostic accuracy and multivariate feature analysis

    Radiology

    (2006)
  • A. Qayyum et al.

    Organ-confined prostate cancer: effect of prior trans rectal biopsy on endorectal MRI and MR spectroscopic imaging

    Am J Roentgenol

    (2004)
  • I. Ocak et al.

    Dynamic contrast-enhanced MRI of prostate cancer at 3 T: a study of pharmacokinetic parameters

    AJR Am J Roentgenol

    (2007)
  • J. Concato et al.

    Molecular markers and mortality in prostate cancer

    BJU Int

    (2007)
  • E. Ackerstaff et al.

    Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells

    Cancer Res

    (2001)
  • J. Kurhanewicz et al.

    Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24-0.1-cm(3)) spatial resolution

    Radiology

    (1996)
  • J. Scheidler et al.

    Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging—clinicopathologic study

    Radiology

    (1999)
  • A. Wetter et al.

    Combined MRI and MR spectroscopy of the prostate before radical prostatectomy

    Am J Roentgenol

    (2006)
  • E. Casciani et al.

    Contribution of the MR spectroscopic imaging in the diagnosis of prostate cancer in the peripheral zone

    Abdom Imaging

    (2007)
  • K.L. Zakian et al.

    Transition zone prostate cancer: metabolic characteristics at H-1 MR spectroscopic imaging—initial results

    Radiology

    (2003)
  • F.V. Coakley et al.

    Prostate cancer tumor volume: measurement with endorectal MR and MR spectroscopic imaging

    Radiology

    (2002)
  • K.K. Yu et al.

    Prostate cancer: prediction of extracapsular extension with endorectal MR imaging and three-dimensional proton MR spectroscopic imaging

    Radiology

    (1999)
  • D. Pucar et al.

    Prostate cancer: correlation of MR Imaging and MR spectroscopy with pathologic findings after radiation therapy—initial experience

    Radiology

    (2005)
  • F.V. Coakley et al.

    Endorectal MR imaging MR spectroscopic imaging for locally recurrent prostate cancer after external beam radiation therapy: preliminary experience

    Radiology

    (2004)
  • J.J. Futterer et al.

    Initial experience of 3 T endorectal coil magnetic resonance imaging and 1H-spectroscopic imaging of the prostate

    Invest Radiol

    (2004)
  • A. Shukla-Dave et al.

    Detection of prostate cancer with MR spectroscopic imaging: an expanded paradigm incorporating polyamines

    Radiology

    (2007)
  • P. Gibbs et al.

    Diffusion imaging of the prostate at 3.0 T

    Invest Radiol

    (2006)
  • P. Kozlowski et al.

    Combined diffusion-weighted and dynamic contrast-enhanced MRI for prostate cancer diagnosis—correlation with biopsy and histopathology

    J Magn Reson Imaging

    (2006)
  • R. Shimofusa et al.

    Diffusion-weighted imaging of prostate cancer

    J Comput Assist Tomogr

    (2005)
  • A. Tanimoto et al.

    Prostate cancer screening: The clinical value of diffusion-weighted imaging and dynamic MR imaging in combination with T2-weighted imaging

    J Magn Reson Imaging

    (2007)
  • T. Tamada et al.

    Age-related and zonal anatomical changes of apparent diffusion coefficient values in normal human prostatic tissues

    J Magn Reson Imaging

    (2008)
  • C.K. Kim et al.

    Value of diffusion-weighted Imaging for the prediction of prostate cancer location at 3 T using a phased-array coil—preliminary results

    Invest Radiol

    (2007)
  • Cited by (49)

    • Incidental detection of a well-differentiated rectal adenocarcinoma by [18F]-Fluorocholine PET/CT in a patient with biochemical relapse of a prostate cancer

      2017, Medecine Nucleaire
      Citation Excerpt :

      The role of choline in tumorigenesis was first discovered by nuclear magnetic resonance spectroscopy studies, which showed high rate of choline in cancer cells [2–4]. Thus, choline labelled with 18fluorine was synthetized for positron emission tomography and presently, is indicated mainly in prostatic adenocarcinoma for the management of recurrent prostate cancer, for the detection of bone metastasis for initial staging and in biological recurrence of prostate cancer in patients with a high metastatic risk [5–8]. However, [18F]-FCH PET/CT is also indicated in staging or restaging of hepatocellular carcinoma [9–11].

    • 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 Physics
      Citation 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 Oncology
      Citation 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 Urology
      Citation 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].

    View all citing articles on Scopus
    1

    Gregory Ravizzini and Baris Turkbey contributed equally to this work.

    View full text