Kinetic Modeling Application to (18)F-fluoroethylcholine Positron Emission Tomography in Patients with Primary and Recurrent Prostate Cancer Using Two-tissue Compartmental Model

Abstract

Although (18)F-fludeoxyglucose-positron emission tomography (PET) is the most applied diagnostic method in tumor staging, its role in prostate cancer (PCA) is limited because glucose metabolism tends to be low unless PCA has high Gleason score. Alternatively, choline PET was introduced as a valuable imaging method. Kinetic analysis of PET acquisition has increasingly gained momentum as an investigative tool because it provides a non-invasive approach to obtain kinetic and metabolic data from tissues of interest including transport and metabolism of the administered material. In this regard, we sought to apply it in (18)F-fluoroethylcholine (FECH)-PET/computed tomography (CT) in patients with PCA. 64 patients, the mean age 69 (range: 47-87 years) with primary/recurrent PCA were encompassed. They underwent (18)F-FECH-PET started with a dynamic acquisition using a 20-frame each 30 s over the prostate region and followed at 1 h post-injection by a static whole body imaging. The kinetic evaluation of the data was performed using the software package PMOD (PMOD Technologies Ltd., Zürich, Switzerland). Significant increase in mean values for K1, K3, FD, standardized uptake value (SUV) and global influx in tumor tissue versus normal tissue (P < 0.05). Moderate but significant correlation (r: 0.28, P = 0.023) between SUV and K1. By contrast, no correlation between SUV and K3 (r: -0.08, P = 0.79). In patients with recurrent tumors, there is no significant difference in all kinetic parameters and SUV (P > 0.1) between the different types of recurrences. The kinetic analysis of dynamic FECH-PET provides a novel method in primary PCA diagnosis and could be of potential value in the delineation of tumor focus.

Keywords: Choline-positron emission tomography; kinetic modeling; prostate cancer.

Figure 1

The dynamic acquisition in the three recurrence types selected for kinetic analysis (a). Bone involvement (b). Lymph node involvement (c). Local recurrence. The upper rows represent the first frame of dynamic phase (radioactivity in arteries); the lower rows represent the end of dynamic phase (note the radioactivity in bladder and ureter); the middle rows represent the mid-dynamic phase

Figure 2

A 77-year-old prostate cancer-patient was referred due to prostate-specific antigen relapse. (a) Axial planes of ¹⁸F-fluoroethylcholine-positron emission tomography/computed tomography (¹⁸F-FECH-PET/CT) fused image and pure PET respectively in the early dynamic phase show a suspected choline uptake in the dorsal bladder wall suggestive for a local recurrence (LR) (notice the radioactivity in the femoral arteries). (b) Axial planes of ¹⁸F-FECH-PET/CT fused image and pure PET respectively in the middle dynamic phase still show the suspected LR (activity decline in the femoral arteries). (c) Contrast-enhanced pelvis CT shows the upper described suspected LR with contrast enhancement. (d) Static image of ¹⁸F-FECH-PET (axial plane) failed to demonstrated the described LR, since it was superimposed by the radioactivity in the bladder, showing thus the importance of dynamic phase in detecting the LR

Figure 3

Compartment model in the light of choline metabolism

Figure 4

(a) ¹⁸F-fluoroethylcholine-positron emission tomography/computed tomography fused image (axial plane) show the volume of interest drawing over tumor focus and adjuvant normal tissue within prostate gland with corresponding time activity curves and input curve (b). (c) Acquisition point at the beginning of dynamic phase (radioactivity in the arteries) (c1, c2) coronal and axial planes at the end of the dynamic phase show a tumor focus in the right prostatic lobe. (d) Fused image (axial plane) in the static imaging (1 h post-injection) shows the tumor focus in the right prostatic lobe corresponding thereby with the dynamic phase

Figure 5

A 64-year-old prostate cancer-patient was referred to our department with prostate-specific antigen (PSA) relapse after radical prostatectomy (PSA serum level 11.5 ng/ml) (a, a1). Baseline ¹⁸F-fluoroethylcholine-positron emission tomography (¹⁸F-FECH-PET) and corresponding computed tomography (CT) (axial plane) demonstrates decent increased uptake in an enlarged lymph node (LN) pararectal (maximum standardized uptake value [SUVmax] 2.3). (b, b1). Follow-up ¹⁸F-FECH-PET and corresponding CT (axial plane), 6 months later exhibits an increasing in both volume and uptake (SUVmax 9.9), confirming thus a LN metastasis as cause of PSA relapse. Parametric images intercept image (c), slope image (c1), intercept/slope fusion (c2) showing an increased phosphorylation rate and volume of distribution in the upper demonstrated LN metastasis

Figure 6

Comparison between tumor and normal tissue in the values of (a) K3 and (b) Influx respectively, the statistic is summarized as box plot

Figure 7

The relationship of SUV with K1 and K3 respectively, presented in scatter plot. (a) SUVmean vs. K1 (r: 0.28P= 0.023). (b) SUV mean vs. K3 (r: −0.08P= 0.79)