increase in their PSA level, which often precedes clinically apparent disease by months to years.
Consequently, imaging of the site and extent of tumor recurrence (local, regional and/or distant recurrence) is of great interest. However, in the past conventional morphological imaging modalities showed limited accuracy for assessment of recurrent prostate cancer.
It is well known that e.g. morphological imaging modalities like computed tomography (CT) or magnetic resonance imaging (MRI) mainly rely on the size criterion for differentiating benign from malignant lymph nodes.
However, small metastatic lymph nodes might be missed, whereas enlarged inflammatory lymph nodes might be misinterpreted as malignant lymph nodes, leading to limited accuracy.
In recent years, however, functional and molecular imaging offered the possibility of imaging molecular or cellular processes of individual tumour biology, often with higher accuracy compared to morphological imaging. One promising technique in this respect is positron emission tomography (PET).
However the most commonly used radiotracer [18F]FDG usually shows no or only faint uptake in well-differentiated prostate cancer and shows substantial uptake only late in the course of the disease and in aggressive, dedifferentiated prostate cancer lesions. Thus alternative tracers have been developed like choline based tracers ([18F]fluorocholine or [11C]choline).
The concept of using choline to image prostate cancer is based on the increased choline uptake and choline turnover in prostate cancer cells, in which key enzymes of choline metabolism, such as choline kinase, are upregulated.
Choline based radiotracers for PET have shown promising results especially for restaging prostate cancer patients after definitive therapy in case of PSA-relapse.
Detection rates have been reported to be 20-30% for PSA-values of less than 1 ng/ml and then continuously increase with rising PSA. For PSA values over 3 ng/l, detection rates of over 80% have been reported.
However, it has to be stressed that large multicenter trials to assess the diagnostic performance of choline based PET tracers for restaging of prostate cancer patients are still missing. Moreover, confirmation of the data by histopathology usually is only limited in the mentioned studies, therefore these data have to be interpreted carefully.
Another interesting radiotracer for imaging of prostate cancer is [111In]capromab-pendetide (ProstaScint), which was developed for scintigraphic imaging and single-photon emission computed tomography (SPECT).
ProstaScint is an FDA-approved and commercially available monoclonal antibody to prostate specific membrane antigen (PSMA). The overall sensitivity and specificity of the use of capromab pendetide for the detection of disease using has varied. In a metaanalysis, 2,154 patients from 15 institutions were analysed.
Although the mean sensitivity was acceptable, at 80%, the reported values ranged from 75% to 99% because of substantial inter-reader variability. Moreover, the fact that ProstaScint binds to an intracellular epitope of PSMA represents a major problem.
It has been suggested that the internal binding of ProstaScint to PSMA occurs predominantly in necrotic or apoptotic cells. Consequently the relevance of ProstaScint imaging remains controversial.
One further disadvantage of ProstaScint but also of choline based tracers is relatively high uptake in normal organs, like intestine which sometimes poses problem when it comes to differentiating physiological from pathological uptake, e. g. in abdominal lymph nodes.
Within this context, hybrid imaging modalities like PET/CT and SPECT/CT have been introduced that combine functional and morphological data and allow for exact image fusion and thus anatomical localization of foci of elevated tracer uptake.
The same might hold true for the combination of MRI and PET. By using MR-PET scanners, one will be able to combine the excellent morphological and functional imaging properties of MRI with the specific biological information of PET.
MRI has shown promising results for restaging of prostate cancer in case of PSA-relapse especially concerning assessment of local recurrence with dynamic contrast enhanced MRI and MR-spectroscopy. PET on the other hand might be especially useful concerning evaluation of lymph node metastases.
Thus hybrid MR-PET might be of synergistic value. Fist sequential MR-PET scanners have recently been installed and the first integrated whole-body MR-PET scanners will be installed in the near future.
This article reviews the contribution of radionuclide imaging and hybrid imaging for assessment of recurrent prostate cancer (local vs. regional vs. distant disease).
We critically discuss the available data on PET/CT and SPECT/CT and provide an overview of experimental tracers and their preclinical and clinical development. Finally, a perspective concerning the potential of future hybrid MR-PET imaging is presented.
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