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Case Report |
1 Department of Nuclear Medicine, Institute H San Raffaele, Via Olgettina 60,
20132, Milan, Italy.
2 University of Milano-Bicocca, Via Olgettina 60, 20126, Milan, Italy.
3 IBFM-CNR, Via Olgettina 60, 20132, Milan, Italy.
4 Department of Radiology, Institute H San Raffaele, 20132, Milan, Italy.
Received October 26, 2001; accepted after revision January 28, 2002.
Address correspondence to F. Fazio.
We describe a patient who had undergone prostatectomy with a progressive increase of prostate-specific antigen (PSA) levels in whom PET with methyl-11C choline was determinant in indicating the presence of bone metastatic disease.
Case Report
A 75-year-old man was treated with radiotherapy in 1994 for a prostate adenocarcinoma (T2b N0 M0) [3]. After the treatment, hormonal therapy was initiated. Results of the clinical and instrumental follow-up, including transrectal echography with prostate biopsies and 99mTc methylene diphosphonate bone scintigraphy, were negative, with a PSA level constantly lower than 2 ng/mL for 3 years.
In 1997, after a progressive rise in PSA level (from 4 to 9 ng/mL in 2 months), transrectal echography with prostate biopsy revealed a recurrence of disease (T3c N1 M0), and a radical prostatectomy was performed.
Findings on the clinical and instrumental follow-up were negative, with PSA levels lower than 0.1 ng/mL until February 2001, when a progressive increase in serum PSA levels up to 0.9 ng/mL was found. Routine examinations at this time included a urologic examination, transrectal echography, and 99mTc methylene diphosphonate bone scintigraphy, all with negative findings for any recurrence of disease.
A written informed consent was obtained from the patient, and a methyl-11C choline PET study was performed 5 min after IV slow-bolus injection of 370 MBq of methyl-11C choline. We used a multiring whole-body scanner (Advance; General Electric Medical Systems, Milwaukee, WI), which allows data collection simultaneously from 35 equally spaced axial slices, 4.25 mm thick. Images of six bed positions, 5 min each, were acquired from pelvis to vertex. The emission scan was followed by a 3-min transmission scan per bed position with a 68germanium—68gallium source external to the patient, to correct for photon attenuation.
Five hours after the methyl-11C choline PET study was performed, a FDG PET study was performed using the same scanner, 45 min after IV slow-bolus injection of 370 MBq of FDG. Bed positions, acquisition time, and transmission scan for attenuation correction were exactly the same as those of the methyl-11C choline PET study. PET raw data were reconstructed using an iterative algorithm and corrected for attenuation using a segmentation algorithm. Axial, coronal, and sagittal images were analyzed by three expert observers. In addition, a quantitative value expressing the amount of tracer accumulation in the target lesion normalized to the injected dose and patient's body surface (bsa) (standardized uptake value: SUVbsa) was calculated.
No abnormal lesions could be found on FDG PET images (Figs. 1A and 1C). On the methyl-11C choline PET study, two different bone lesions were found (Figs. 1B and 1D): one in the proximal left femoral portion (SUVbsa = 6.30) and one in the right sacroiliac joint (SUVbsa = 9.31).
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Ten days after the PET studies, MR imaging showed both methyl-11C choline—positive lesions as probably malignant (Figs. 1E and 1F). The size of the two lesions calculated on MR imaging was 13.4 x 10.8 mm and 13.8 x 7.8 mm for the proximal left femoral portion and right sacroiliac joint, respectively.
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Discussion
Prostate adenocarcinoma is one of the most common neoplasms in men, and its incidence is increasing, probably because of a more accurate and earlier diagnosis due to the introduction of PSA measurement, the most sensitive test for both the staging and the follow-up of prostate cancer [4].
After radical prostatectomy, a progressive increase in PSA levels indicates recurrence of disease, but PSA levels do not indicate whether the elevation is due to local progression or distant metastases, and they, in turn, do not localize them. In a patient who has undergone prostatectomy, knowledge of the site of recurrence is important because it may determine therapy.
To identify local recurrences, various examinations are available, including digital rectal examination and transrectal echography. However the sensitivity and specificity of these two techniques are not satisfactory (sensitivity and specificity, 76-67% and 44-91%, for transrectal echography and digital rectal examination, respectively) [5]. A more accurate technique to reveal local recurrence in men who underwent radical prostatectomy is MR imaging, showing a sensitivity of 77%, using a body coil, that can rise to 100%, using an endorectal coil [6].
Prostate carcinoma frequently metastasizes to bone. Because this tumor primarily elicits a vigorous osteoblastic response, 99mTc methylene diphosphonate bone scintigraphy is usually performed in the staging and restaging of prostate cancer. However, MR imaging is superior to bone scintigraphy in the detection of bone metastases, particularly when these tumors are osteolytic or located in the bone marrow. Diffuse bone metastases to the spine can be seen on MR imaging but are missed on bone scanning when the appearance is symmetric. Nevertheless, 99mTc methylene diphosphonate bone scintigraphy is routinely performed because it examines the entire body, including the appendicular skeleton, in a relatively short time. On the other hand, although whole-body MR imaging techniques are available, they are difficult and time-consuming to perform [7].
An imaging technique capable of reliably detecting both local and distant recurrences at the same time would facilitate the instrumental follow-up of patients with recurrent prostate cancer.
FDG PET is showing increasing usefulness in the monitoring of therapeutic responses, detection, and staging of a wide variety of neoplasms [8]. However, it seems less accurate in patients with prostate cancer; in most primary prostate tumors, FDG uptake is low, probably because prostate adenocarcinoma is a slow-growing neoplasm. In addition, the physiologic urinary excretion of FDG can interfere with imaging in the pelvis. On the whole, detectability of bone metastases from prostate cancer with FDG PET is lower than that of conventional 99mTc methylene diphosphonate bone scintigraphy [9].
Recently, MR spectroscopy has shown an elevated level of phosphatidylcholine in neoplastic tissue; all cells use choline as a precursor for the biosynthesis of phospholipids, in particular phosphatidylcholine, which is the essential component of all eukaryotic cell membranes such as those of neoplasms [10]. These observations have been the rationale for the introduction of a new positron emission radiotracer for oncologic PET studies—methyl-11C choline. Previous PET studies have shown that neoplastic tissue is characterized by higher uptake of methyl-11C choline than normal tissue, because of the increase of phospholipids synthesis [1]. In fact, PET with methyl-11C choline successfully depicts various tumors with a high signal-to-background ratio, particularly those located in the pelvis in which the background radioactivity related to the tracer is low. Although methyl-11C choline accumulation is present in the healthy prostate, its excretion via the urinary tract is negligible so that its accumulation in the bladder is low.
In our patient, methyl-11C choline PET readily identified the presence of bone metastases, whereas these were not detectable by either 99mTc methylene diphosphonate bone scintigraphy or FDG PET.
Although confirmation of the metastatic nature of the bone lesions through histologic examination was not available, metastasis was strongly suggested by the combination of methyl-11C choline PET findings with those of MR imaging.
We conclude that methyl-11C choline is a promising tracer for imaging prostate cancer and its metastases and that a systematic comparison of this technique with conventional morphologic examination and with FDG PET would help in defining the clinical impact of methyl-11C choline PET in the follow-up of patients with prostate cancer.
References
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