ABSTRACT

Objectives:

This study aimed to investigate the relationship between the standard uptake value (SUV) of body weight and SUV corrected for lean body mass (SUL) parameters obtained from the prostate gland in gallium-68 (⁶⁸Ga)-prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) with Gleason grade (GG) groups, D’Amico risk groups, and presence of metastases.

Methods:

Patients with prostate adenocarcinoma who underwent ⁶⁸Ga-PSMA PET/CT for staging at our center between February 2017 and October 2018 were evaluated retrospectively. Maximum SUV (SUV_max), SUV_peak, SUL_max, SUL_peak, SUV_mean, and SUL_mean values of the prostate tumor were obtained. The difference in these values between GG groups (≥3, <3) and D’Amico risk (low-moderate/high) groups was evaluated with the Mann-Whitney U test. The area under the curve values of SUV and SUL parameters were compared. In addition, SUV_mean and SUL_mean values were obtained from the right liver lobe, and their correlation with body weight was evaluated.

Results:

A total of 79 patients were included in the study. Significant differences were found in the prostate SUV_max, SUL_max, SUV_peak, SUL_peak, SUV_mean, and SUL_mean values between the GG (≥3 and <3) groups and between D’Amico risk (low-moderate and high) groups. However, no significant difference was found in the discriminative power of any SUV or SUL parameter when compared with each other. A significant difference in any SUV and SUL parameters was found in patients with and without metastasis. Neither liver SUV_mean value nor SUL_mean value correlated with the body weight.

Conclusion:

The superiority of SUL values obtained from ⁶⁸Ga-PSMA PET to SUV was not determined in our study. SUV parameters can also be used for quantitative analysis in ⁶⁸Ga-PSMA PET.

Keywords:

SUV, SUL, lean body mass, prostate specific membrane antigen

Introduction

Positron emission tomography/computed tomography (PET/CT) is becoming a standard component of the diagnosis and staging in the field of oncology. Especially, ¹⁸flourine-fluorodeoxyglucose (¹⁸F-FDG) PET/CT is used to quantify radiopharmaceutical uptake and quantitatively determine treatment response in the evaluation of the metabolic response in various tumors (1,2,3). PET images are analyzed in clinical practice either qualitatively using visual comparison of metabolism in lesions with normal tissue or semi-quantitatively using standard uptake values (SUV). SUV is obtained as the tissue concentration (MBq/mL) divided by the injected activity (MBq/g) per body weight (BW). Factors affecting SUV have been discussed in many studies (4,5,6). Since fat contributes to BW but accumulates very little ¹⁸F-FDG in a starvation state, SUV is relatively increased in patients who are obese than in thinner ones. A study found that lean body mass (LBM) SUV (SUL) correction is a more suitable quantitative method than BW or body surface area for patients who are obese (7).

Prostate-specific membrane antigen (PSMA) is a highly expressed human transmembrane protein that is low or moderate in normal or hyperplastic prostate tissues and high in primary adenocarcinomas and distinguishes malignant lesions from benign lesions with high accuracy and positively correlates with the degree of expression, tumor aggression, metastatic disease, and recurrence (8,9,10,11). In the literature, studies have shown that the SUV values obtained from a prostate tumor are higher as the Gleason score (GS) and prostate-specific antigen (PSA) value increase. Gafita et al. (12) investigated whether SUL is a more appropriate quantitative method than SUV, which is normalized by BW in gallium-68 (⁶⁸Ga)-PSMA 11 PET/CT. They found that correction with lean BW disrupts positive correlations between absolute SUV and BW and that SUL may be preferred over SUV for quantitative analysis in ⁶⁸Ga-PSMA 11 PET (12).

This study aimed to investigate the relationship between the SUV and SUL parameters obtained from the prostate tumor according to Gleason grade (GG) groups, D’Amico risk groups, and presence of metastasis in ⁶⁸Ga-PSMA PET/CT and to determine whether SUL is superior to SUV.

Materials and Methods

Results

The study included 79 patients with a mean age of 65±7 (range, 44-78) years and mean BW of 81.5±14.5 (range, 53-125) kg. The median PSA value was 16 (range, 0.02-527.00) ng/mL. A total of 13 patients had a history of radical prostatectomy.

In this study, 7 (9%) patients had GG 1, 21 (27%) had GG 2, 12 (15%) had GG 3, 15 (19%) had GG 4, and 24 (30%) had GG 5. In ⁶⁸Ga-PSMA PET/CT, 41 (52%) patients did not have metastasis, while 38 patients had PSMA expression suggesting metastasis. Moreover, 33 (41.8%) patients had lymph node metastasis. Five of these patients had PSMA expression in cervical/mediastinal lymph nodes, 16 in abdominal lymph nodes, and 33 in pelvic lymph nodes. In addition, 19 (24.1%) patients had PSMA expression suggesting bone metastasis, whereas 2 (2.5%) patients had PSMA expression suggesting pulmonary metastasis. In the study group, no patient had liver metastasis. According to the D’Amico risk groups, two patients had low risk, 18 (22.8%) patients had moderate risk, and 59 (74.7%) patients had high-risk.

The mean ± standard deviation and median (range) values from the prostate tumor were calculated as follows: SUV_max, 11.5±9.3 and 8.0 (3.0-49.8); SUL_max value, 8.4±6.1 and 6.1 (2.2-34.4); SUV_peak value, 8.6±7.2 and 5.8 (2.4-37.6); SUL_peak value, 6.3±4.5 and 4.5 (1.7-25.9); SUV_mean value, 5.0±2.6 and 4.2 (1.9-13.8); and SUL_mean value, 3.7±3.3 and 3.2 (1.3-9.4).

A significant difference was found in the prostate SUV_max, SUL_max, SUV_peak, SUL_peak, SUV_mean, and SUL_mean values between patients with GG ≥3 and <3 (Table 1). However, when comparing AUC values of SUV and SUL parameters in distinguishing GG groups, no SUV/SUL parameters were superior to the other (Table 2).

No significant difference was observed in any SUV and SUL parameters between patients with GS 3+4 and 4+3.

Prostate SUV_max, SUL_max, SUV_peak, SUL_peak, SUV_mean, and SUL_mean values were significantly higher in the high-risk group than in the other D’Amico risk groups (Table 1). However, no SUV/SUL parameter was superior to others in distinguishing risk groups (Table 2).

While all SUV and SUL parameters were higher in patients with a PSA value ≥10 ng/mL than in those with <10 ng/mL (Table 1), no significant difference was found in the discrimination power of any SUV and SUL parameters (Table 2).

No significant difference was found in any SUV and SUL parameters in patient groups with and without metastasis.

The mean liver SUV_mean value was calculated as 4.0±1.1 (1.8-7.6), and the liver SUL_mean value was 3.0±1.4 (1.4-5.5). The liver SUV_mean and SUL_mean values did not correlate with BW (p=0.387 and 0.132, respectively).

Discussion

In this study, a significant correlation was found with the BW of neither SUV_mean nor SUL_mean obtained from the liver. Gafita et al. (12) reported that SUL can be preferred over SUV in ⁶⁸Ga-PSMA 11 PET/CT. In this study, while the liver SUV_mean value showed a significant correlation with BW, no significant correlation was found in the SUL_mean value. Despite the few studies on this subject, similar to our study, Li et al. (2) evaluated the ¹⁸F-DCFPyL uptake but could not detect a significant correlation between liver SUV_mean and SUL_mean values and BW; as a result, they suggested using the SUV.

Several studies have also shown that PSMA SUV data are successful in differentiating GG groups and risk groups (18,19,20,21). Likewise, we were able to obtain significant differences in SUV parameters between these groups. However, our study is the first to evaluate the relationship between the success of SUL and SUV parameters obtained from ⁶⁸Ga-PSMA PET in differentiating GG groups and risk groups. In our study, SUL parameters obtained from ⁶⁸Ga-PSMA PET were not superior to SUV parameters in distinguishing GG groups and in distinguishing risk groups. Moreover, the studies that quantified uptake with body-weight-corrected SUV and LBM-corrected SUV have shown that the repeatability coefficient of SUL_max and SUV_max within the same patient in a test-retest setting is comparable (22,23,24). These results show that SUL and SUV parameters are not superior to each other in ⁶⁸Ga-PSMA PET in clinical practice.

Prostate SUV and SUL parameters were significantly higher in patients with GG ≥3 than in GG ≤2, and this is similar to the findings in the literature. Onal et al. (25) reported that SUV_max values obtained from primary tumors in 191 patients were significantly higher in patients with GS >7.

In their study, Uprimny et al. (18) did not find a significant difference in SUV_max values between GG 2 and 3 tumors. Similarly, Ergül et al. (19) did not found a significant difference in SUV_max values between grade 2 and 3 tumors. In addition, in our study, neither SUV_max values nor other SUV and SUL values were detected differently in tumors with GG 2 and 3.

In a previous study, Ergül et al. (19) analyzed 78 patients and found a significant difference in SUV_max values of prostate tumors with and without metastasis. However, Liu et al. (20) did not observe a significant difference in SUV_max in patients with and without metastasis. In the present study, similar to the study of Liu et al. (20), no significant difference was found in any SUV and SUL parameters between these groups.

Patients

Patients with prostate adenocarcinoma who underwent ⁶⁸Ga-PSMA PET/CT for staging at our center between February 2017 and October 2018 were evaluated retrospectively. GG groups of patients were obtained from prostatectomy material in patients undergoing prostatectomy and fine-needle biopsy results in other patients. D’Amico criteria was considered for risk stratification [low risk group (PSA <10 ng/mL and GS <7 and T1-T2a), intermediate-risk group (PSA 10-20 ng/mL or GS 7 or T2b-T2c), and high-risk group (PSA >20 ng/mL or GS 8-10 or T3-T4)] (13). Patients were divided into two groups according to their GG (≥3 vs <3).

PET Image Analysis

Patients signed the informed consent form, and radiation safety and imaging protocol were described. An average of 3.2 millicurie (mCi) ⁶⁸Ga-PSMA Imaging and Therapy was injected intravenously. Low-dose CT was used for attenuation correction an hour after injection. PET images were obtained for 1.5 min in each bed position in the supine position from the vertex to the toe tip in Philips Gemini TF PET/CT (Eindhoven, Netherlands). Row action maximum likelihood algorithm was used for reconstruction.

Patients who had PSMA expression on ⁶⁸Ga-PSMA PET/CT images, which could be differentiated from background activity and thought to be related to prostate adenocarcinoma metastasis (PSMA-RADs 4 and 5) were considered to have metastatic disease (14).

Weights and heights of the patients were measured before imaging. LBM was calculated with the formula developed by Janmahasatian (15,16).

LBM = (9.27×10³×BW)/(6.68×10³+216×BMI)

In the prostate gland, a region of interest was drawn on the area where PSMA expression was observed above background activity. Maximum SUV (SUV_max), SUV_mean, and SUV_peak values were obtained from this area. SUL_max, SUL_mean, and SUL_peak values were calculated from SUV_max, SUV_mean, and SUV_peak values using the LBM value obtained from the Janmahasatian formula.

SUL = SUV × LBM/BW

In addition, a 3-cm volume of interest (VOI) was drawn to the right liver lobe to determine liver background activity. Liver SUV_mean and liver SUL_mean values were obtained from this VOI (17).

Statistical Analysis

The free version of the Statistical Package for the Social Sciences v. 26.0 was used for statistical analysis. The correlations among liver SUV_mean, liver SUL_mean, and BW were evaluated by Spearman correlation analysis. A p<0.05 value was considered significant.

The difference in SUV_max, SUL_max, SUV_mean, SUL_mean, SUV_peak, and SUL_peak values from the prostate tumor between low-moderate and high-risk groups was analyzed with the Mann-Whitney U test. In addition, the difference in the SUV and SUL values between GG groups, between PSA groups (≥10 and <10 ng/mL), and between D’Amico risk groups (low-moderate and high) was evaluated with the Mann-Whitney U test.

The potential of SUV and SUL parameters in distinguishing GG groups and risk groups was evaluated by the receiver operating characteristics analysis. The area under the curve (AUC) values were compared, and significant difference between them was evaluated.

Ethics Approval

Dokuz Eylül University Ethics Committee approval was obtained (decision no: 2020/18-37, date: 10.08.2020). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients gave their informed consent before their inclusion in the study.

Conclusion

In this study, the superiority of SUL values obtained from ⁶⁸Ga-PSMA PET to SUV was not determined. We think that both SUV and SUL parameters can be used for quantitative analysis in ⁶⁸Ga-PSMA PET.

Study Limitations

First, the retrospective design limits the generalizability of the results. Second, histopathological correlation is not technically and ethically possible from all foci considered metastasis. Finally, prostatectomy could not be applied to all patients, and the GS of some patients could only be obtained from the biopsy sample.

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Is SUV Corrected for Lean Body Mass Superior to SUV of Body Weight in 68Ga-PSMA PET/CT?