¹⁸F-Fluorocholine PET/MRI in Restaging of Prostatic Carcinoma in Relation to PSA Level and Detection of Active Disease

Discussion

It is possible for prostate cancer to be detected incidentally in Western men with increased use of PSA to detect high-risk individuals, but the shift in morbidity and mortality indicates that the disease is occurring more often than in the past (7).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Solitary metastasis (arrows) found in the sternum in a patient with serum prostate-specific antigen level rising over 6 months from 0.001 ng/ml to 0.296 ng/ ml. A: Whole-body maximum intensity projection positron emission tomography (PET) image. B: Transaxial PET image. C: T2 STIR image. D: T1 CRE water image.

Prostate cancer requires multiple lines of treatment, starting with radical prostatectomy or radical irradiation. Radical prostatectomy is indicated in patients with locally operable tumors and also in the absence of distant metastases and metastases outside the pelvic lymph nodes. Biopsy and tumor classification using Gleason score play a key role in determining the prognosis of the disease and further treatment. However, since some tumors, including clinically evident ones, escape diagnosis through biopsy sampling, even several times in a row, FCH-PET/CT leads to more accurate biopsy targeting and increases the success of biopsy (7). A significantly higher incidence of distant metastases, especially of bone, but also more frequent involvement of lymph nodes is expected in patients with a Gleason score of 8 or more (1, 7, 8). When comparing PET/CT with findings of subsequent lymphadenectomy, it was found that the sensitivity for detecting lymph node metastases was only about 33%, although with high specificity of 92% (5-8). It appears that increased accumulation of ¹⁸F-FCH can be considered as a highly suspicious sign of metastasis, although not all metastases accumulate FCH (9). Lower sensitivity can be attributed to frequent metastatic infiltration of lymph nodes much smaller than 10 mm, as only about 10% of patients had metastases in the lymph nodes exceeding this size (2).

In patients with recurrent PSA elevation after radical therapy, the increased PSA level (as ng/ml) is a sign of the presence of viable tumor tissue of prostate cancer. In several studies, the authors documented a value of about 4 ng/ml as the critical value for detecting a pathological focus of FCH accumulation (3, 6, 10-13); our own results showed that the rate of detection of recurrence is improved even at a serum PSA level of 2.0 ng/ml. An improved detection rate was documented in patients when ⁶⁸Ga-labeled ligand of PSMA (⁶⁸Ga-PSMA-HBED) was used (4, 5). Our own experience has shown that the most significant thresholds for the detection of recurrence are 2 ng/ml, above which tumor tissue manifests FCH accumulation in more than 98% of all cases, and 5 ng/ml, above which accumulation in tumor tissue is detected in all cases. In addition to these findings, a very satisfactory detection rate was found in the group of patients with PSA levels below 2 ng/ml. We were also able to detect solitary metastasis in a patient with a PSA level rapidly rising within half a year from 0.01 to 0.296 ng/ml (11), that finding documented that PET/MRI can help to detect recurrence very early in selected cases. The onset of skeletal findings, and its load, predicts the development of skeletal events in patients with metastatic skeletal spread of the disease (14).

When evaluating prostate tissue, lymph nodes and the skeleton, FCH-PET faces several problems. Choline distribution to the tissues through blood flow is relatively rapid depending on the perfusion level, and in some tissues, accelerated FCH extraction from the bloodstream occurs in proportion to their perfusion. The primary points of interest are activated lymph nodes and also activated bone marrow. When detecting bone metastases, our experience showed that it is necessary to search for local bone findings, and if FCH accumulation is focally associated with focal osteosclerosis or focal osteolysis, the findings should be evaluated as metastasis when concordant MRI findings are present – typically increased intensity on T2 STIR or T1-weighted water MRI after application of contrast agent obtained using the Dixon method of T1-weighted gradient echo MRI. Conversely, diffuse accumulation in vertebral bodies accompanied by increased signal on T2 STIR could be the consequence of chemotherapy or the therapeutic androgen blockage. The decline of FCH accumulation was observed after erythropoetin application (15), similar observations were documented also in our own sample of patients.

The relationship between de novo bone formation due to osteoblastic stimulation by prostate cancer metastasis and FCH accumulation has not yet been fully elucidated. Apparently, a proportional relationship is present between the population of active prostate cancer cells and the level of FCH accumulation. In some bone metastases with NaF accumulation, FCH accumulation may not be present and vice versa. Bisphosphonates may play a role in bone tissue behavior, such as the most commonly used zolendronate, which suppresses the activity of osteoclasts and indirectly stimulates osteoblastic activity and the increase of the NaF accumulation. Therefore, some authors indicate the possibility of dual imaging of bone involvement in prostate cancer, first with FCH imaging (9, 10), and thereafter also with NaF imaging in patients with negative or ambiguous findings and positive biochemical results (16). Further studies are needed to show whether these imaging techniques are complementary. Our own experience has shown that the MRI part of PET/MRI improved the discrimination between bone metastases and bone turnover due to other reasons.

Regarding PET imaging with choline derivatives, ¹¹C-labeled products are unusable in conventional clinical practice, except for centers equipped with a cyclotron, due to their very short half-life of only 20 minutes. In the European Union, ¹⁸F-labeled FCH is dominant among radiopharmaceutical labeled with ¹⁸F; it seems to be capable of being incorporated into the phosphatidylcholine precursor. Increased choline turnover is typical for tissues with high proliferation activity dependent on lipid metabolism (1, 2). Imaging with PSMA ligands has been increasing in recent years (4, 5). These substances are more selective in their binding to prostatic carcinoma tissue in metastases: studies using PSMA ligands and PET/CT in the evaluation of restaging in prostate carcinoma showed an increased number of detected lesions in comparison to PET/CT with FCH in patients with raised PSA (4, 5). But, our results demonstrated a satisfactory detection rate. The reason is the high tissue contrast within bone marrow when magnetic resonance is used in the evaluation of the correlation between morphological and metabolic images. Thus, the improved detection rate of the pathologies is related to the use of integrated PET/MRI system in those patients who have low-level raised PSA value.

With rare exceptions (such as small cell prostate carcinoma), fluorodeoxyglucose PET imaging is irrelevant in prostate cancer, since typical acinar prostate carcinoma does not accumulate ¹⁸F-fluorodeoxyglucose, irrespective of Gleason score. In some studies, early dynamic imaging is combined with early scan complemented by late PET scan, but this combination currently does not produce better results, and even early imaging fails to provide better results than late imaging (12).