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Objective To compare the efficiency of 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and 18F-labeled sodium fluoride (18F-NaF) PET/CT in the diagnosis of bone metastasis in the patients with prostate cancer.Methods The prostate cancer patients suspected of bone metastasis who underwent 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT from January 2018 to January 2021 were included in this study.The number of lesions,maximum standardized uptake value (SUVmax),and tumor-to-background (T/B) ratio were compared between the two methods.Results 18F-NaF PET/CT detected more metastases than 68Ga-PSMA-11 PET/CT (310 vs.264,P<0.001).The median SUVmax[23.2 (16.4,33.4) vs.4.1 (2.5,5.6)] and median T/B ratio[7.0 (4.9,9.9) vs.6.7 (3.7,9.6)] of 18F-NaF PET/CT were higher than those of 68Ga-PSMA-11 PET/CT (all P<0.001).With the number of lesions as the indicator,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of 18F-NaF PET/CT were 100.0%,92.0%,92.0%,98.7%,and 100.0% respectively,and those of 68Ga-PSMA-11 PET/CT were 85.2%,94.0%,79.2%,98.9%,and 50.5%,respectively.Conclusion 18F-NaF PET/CT is superior to 68Ga-PSMA-11 PET/CT in the detection of bone metastases of prostate cancer.
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Objective:To evaluate the diagnostic value of the 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in seminal vesicle invasion (SVI) of prostate cancer. Methods:Clinical and pathological materials of 88 patients (age: 51-84 years) who underwent radical prostatectomy (RP) between May 2019 and December 2021 in the First Affiliated Hospital of Xi′an Jiaotong University were analyzed retrospectively. All patients underwent 18F-PSMA-1007 PET/CT examination for primary staging before surgery. The diagnostic efficiency of 18F-PSMA-1007 PET/CT in SVI was obtained using postoperative pathological results as the " gold standard" and ROC curve was drawn. Furthermore, univariate and multivariate logistic regression analyses were used to screen the influencing factors for 18F-PSMA-1007 PET/CT prediction of SVI. Results:The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 18F-PSMA-1007 PET/CT in diagnosing SVI were 79.55%(70/88), 72.73%(16/22), 81.82%(54/66), 57.14%(16/28) and 90.00%(54/60), respectively. The ROC AUC was 0.77. Results of univariate logistic regression showed that total prostate specific antigen (tPSA), primary SUV max, Gleason score, International Society of Urological Pathology (ISUP) grade group were associated with 18F-PSMA-1007 PET/CT prediction of SVI. Results of multivariate logistic regression showed that Gleason score (odds ratio ( OR)=2.04, 95% CI: 1.19-3.50, P=0.009) was a predictor of SVI in prostate cancer. Conclusion:18F-PSMA-1007 PET/CT has certain diagnostic value in SVI of prostate cancer, and combining with Gleason score can improve the diagnostic efficiency.
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Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.
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Objective:To investigate the effects of different labeling conditions on the yield of Al 18F-labeled 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA)-prostate specific membrane antigen (PSMA)-137, and to determine the experimental condition for obtaining Al 18F-PSMA-137 probe in high yield. Methods:The effects of different pH values, buffer systems (acetic acid-sodium acetate buffer system and potassium hydrogen phthalate (KHP) buffer system), AlCl 3-ligand ratios, ligand amounts, ethanol volumes and reaction temperatures on the labeling rate were investigated in detail. Results:The pH value of the reaction solution had a significant effect on the labeling rate, and the optimal range was 4.0-4.5. When the pH value was higher than 4.5, the labeling rate decreased significantly. Both the acetic acid-sodium acetate buffer system and the KHP buffer system could be used to label NOTA-PSMA-137 with Al 18F, and the KHP buffer system obtained higher labeling rate. The ratio of AlCl 3-ligand affected the labeling rate, and the highest labeling rate could be obtained when the ratio of AlCl 3-ligand was 0.54-0.62. When the ratio of AlCl 3-ligand was fixed, increasing the amount of ligand could improve the labeling yield. Adding hydrophilic organic solvent ethanol to the reaction system could significantly increase yield, with the highest labeling rate being achieved at a volume of 100 μl ethanol. The most suitable reaction temperature was 100 ℃, and when the temperature raised to 110 ℃, the labeling rate decreased significantly. The most suitable labeling conditions for NOTA-PSMA-137 were as following: 25 μl KHP buffer (0.50 mol/L, pH=4.0), 7.0 μl AlCl 3 solution (20 mmol/L), 200 μl Na 18F solution (74-80 MBq) and 230 μg ligand NOTA-PSMA-137 were mixed in a vial, then stood for 5 min and 100 μl ethanol was added, and all reagents were heated at 100 ℃ for 10 min. The yield of Al 18F-PSMA-137 under above conditions were 85.7%-88.5%. Conclusion:Optimization of labeling condition can improve the yield of Al 18F-PSMA-137 and the stability of the labeling.
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Objective:To evaluate the value of 18F-prostate specific membrane antigen (PSMA)-3Q PET/CT imaging in prostate cancer patients with serum prostate specific antigen (PSA) less than 1.00 μg/L after radical prostatectomy. Methods:From May 2021 to August 2022, 18F-PSMA-3Q PET/CT images and clinical data of 58 patients with prostate cancer (age 52-82 years) after radical prostatectomy with PSA less than 1.00 μg/L in Chinese PLA General Hospital were analyzed retrospectively. According to the level of PSA, patients were divided into three groups (0-0.19 μg/L group, 0.20-0.49 μg/L group, and 0.50-0.99 μg/L group). 18F-PSMA-3Q PET/CT images were analyzed according to the standardized evaluation criteria of molecular imaging, and lesions with the scores of molecular imaging PSMA (miPSMA)≥1 were defined as recurrent or metastatic lesions. The detection rates of 18F-PSMA-3Q PET/CT for patients in different PSA level groups were compared ( χ2 test). The PSA levels of patients with positive and negative scans were compared by using independent-sample t test. Results:Of the 58 patients, 36(62.1%, 36/58) patients and 85 lesions were found by 18F-PSMA-3Q PET/CT. There was 91.7%(33/36) with oligofocal lesions (1≤number of foci≤3) and 8.3%(3/36) with multiple lesions (number of foci>3). According to the location, 5.2%(3/58) of the recurrent lesions were found in the prostatic bed, 39.7%(23/58) in the bone lesions, 37.9%(22/58) in the pelvic lymph nodes, 12.0%(7/58) in the retroperitoneal lymph nodes and 5.2%(3/58) in the left clavicular lymph node metastases. There were 15 cases in 0-0.19 μg/L group, 22 cases in 0.20-0.49 μg/L group, and 21 cases in 0.50-0.99 μg/L group. The detection rates of 18F-PSMA-3Q PET/CT in the above groups were 5/15, 59.1%(13/22) and 85.7%(18/21), respectively ( χ2=10.33, P=0.006). There was significant difference in PSA level between patients with positive ( n=36) and negative ( n=22) 18F-PSMA-3Q PET/CT scans ((0.48±0.28) vs (0.28±0.25) μg/L; t=2.67, P=0.010). Conclusions:18F-PSMA-3Q PET/CT can be used to detect the recurrence or metastasis in prostate cancer patients with PSA level lower than 1.00 μg/L after radical prostatectomy. In this kind of patients, the common sites of lesions are bone, pelvic lymph nodes, retroperitoneal lymph nodes, left clavicular lymph nodes and prostatic bed, and oligofocal patients are more common.
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Objective:To assess the performance of Al 18F-prostate specific membrane antigen (PSMA)-BCH PET/CT in the detection and localization of early recurrent prostate cancer after radical prostatectomy. Methods:From July 2021 to July 2022, a cohort of 51 patients (age: 49-80(64.8±6.9) years) who underwent Al 18F-PSMA-BCH for biochemical recurrence with the prostate specific antigen (PSA) level less than 2 μg/L in Peking University Cancer Hospital & Institute were retrospectively analyzed. The patients were stratified into 4 groups (PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L, 1 μg/L≤PSA<2 μg/L groups) according to different PSA levels. Lesions detected by Al 18F-PSMA-BCH PET/CT were recorded as prostate bed (including bed of seminal vesicles); pelvic, paraaortic, mediastinal/supraclavicular and axillary lymph nodes; bone lesions and visceral lesions. The detection rates among different groups were compared by Fisher exact test. Results:Of 51 patients, 30(58.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer, with 60.0%(18/30) had disease confined to the pelvis, including 26.7%(8/30) had prostate bed recurrence, 26.7%(8/30) had pelvic lymph nodes, 6.6%(2/30) had prostate bed recurrence with pelvic lymph nodes, while 40.0%(12/30) had extra pelvic disease. The detection rates of Al 18F-PSMA-BCH PET/CT in PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L and 1 μg/L≤PSA<2 μg/L groups were 39.1%(9/23), 6/11, 8/9 and 7/8, respectively. There were no significant differences of detection rates between PSA<0.2 μg/L group and 0.2 μg/L≤PSA<0.5 μg/L group ( P=0.397) and also between 0.5 μg/L≤PSA<1 μg/L group and 1 μg/L≤PSA<2 μg/L group ( P=0.929). Conclusion:Al 18F-PSMA-BCH has a high detection rate for early recurrent prostate cancer, even at low PSA levels less than 0.2 μg/L.
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Objective:To explore the value of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in newly diagnosed prostate cancer patients with different risk stratifications, and to compare the performance of this modality with conventional imaging in detecting metastases. Methods:From June 2019 to July 2020, the clinical and imaging data of 60 patients (age range: 44-88 years, median age 69 years) who underwent 68Ga-PSMA-11 PET/CT imaging in Fudan University Shanghai Cancer Center were retrospectively analyzed. Spearman rank correlation analysis was used to explore the correlation of SUV max in primary foci with prostate specific antigen (PSA) and Gleason score (GS). Based on the D′Amico risk stratification (PSA>20 μg/L and ≤20 μg/L, GS>7 and ≤7), the detection rates of 68Ga-PSMA-11 PET/CT for metastases were evaluated by χ2 test, and the differences of SUV max were analyzed by Mann-Whitney U test. Patients were divided into high-risk (PSA>20 μg/L and GS>7), medium-risk (PSA>20 μg/L and GS≤7, or PSA≤20 μg/L and GS>7), and low-risk (PSA<20 μg/L and GS<7) groups according to PSA levels and GS. Compared with conventional imaging (bone imaging, CT or MRI), the ability of 68Ga-PSMA-11 PET/CT to detect metastatic tumors, and the utility to change the prostate cancer stage were evaluated by Fisher′s exact test. Results:High uptake of 68Ga-PSMA-11 was observed in primary lesions of 60 patients, and SUV max was positively correlated with GS or PSA ( rs values: 0.42, 0.38; P values: 0.001, 0.002). The detection rates of lymph node and bone metastases in the group with PSA>20 μg/L were 11/18 and 13/18, respectively, which were higher than those in the group with PSA≤20 μg/L (28.57%(12/42) and 35.71%(15/42); χ2 values: 6.56, 7.56, P values: 0.010, 0.006. However, there was no statistical significance in the SUV max of these lesions( z values: -1.04, -0.96; P values: 0.299, 0.337). There was a statistical difference in the detection rates of lymph node and bone metastases between the group with GS>7 and the group with GS≤7 (lymph node: 54.05%(20/37) vs 13.04%(3/23), χ2=10.09, P=0.001; bone metastases: 59.46%(22/37) vs 26.09%(6/23), χ2=8.19, P=0.004), as well as the SUV max of bone metastases( z=-2.02, P=0.044). In the high-risk group, 68Ga-PSMA-11 PET/CT had the higher detection rate of metastases than conventional imaging (16/17 vs 10/17; P=0.039) and it changed 25.0%(15/60) of the patients′ staging. Conclusions:PSA and GS affect the detection rate of 68Ga-PSMA-11 PET/CT. In patients with high-risk prostate cancer, 68Ga-PSMA-11 PET/CT is superior to conventional imaging in detecting metastases. When PSA>20 μg/L and GS>7, it is better to use 68Ga-PSMA-11 PET/CT in prostate cancer staging.
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With wide application of 68Ga-prostate specific membrane antigen(PSMA)positron emission tomography(PET)technology in the diagnosis of prostate cancer (PCa), researchers have paid more attention to nodal staging in PCa by 68Ga-PSMA PET. Currently, 68Ga-PSMA PET has been used to detect lymph node metastases (LNMs) in primary prostate cancer patients and recurrent prostate cancer patients. Compared with the traditional imaging techniques, 68Ga-PSMA PET can detect LNMs with higher sensitivity, specificity and accuracy, which has great impact on treatment management of PCa patients. This article reviewed the research progress of detection of LNMs by 68Ga-PSMA PET in prostate cancer patients.
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Objective:To explore the feasibility of radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-PSMA PET/CT. Methods:Patients were enrolled in this single-arm prospective study from March 2019 to January 2022 in the Second Hospital of Tianjin Medical University. Eligible patients were aged ≤80 years with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. Based on mpMRI and 68Ga-PSMA PET/CT, patients were diagnosed with highly suspected localized prostate cancer with no evidence of distant lymphatic, bone or visceral metastases. Patients were excluded if they had obvious important organs dysfunction, suspected metastatic lesions or history of other malignant tumor. After fully informed of the surgical risks and possibilities of final pathology, patients received laparoscopic or robot-assisted laparoscopic radical prostatectomy. According to final pathological results, the diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was evaluated. Pathological features were compared between low 68Ga-PSMA PET/CT maximum standardized uptake value (SUV max) group (SUV max<10) and high SUV max group (SUV max≥10). Baseline characteristics were compared between clinically significant prostate cancer (CsPCa) and clinically insignificant prostate cancer (cisPCa) + high grade prostatic intraepithelial neoplasia (HGPIN) patients. Additional analysis of the correlation between baseline parameters and different subgroups including pathological stage, ISUP grades and risk groups were performed in CsPCa patients. Results:31 patients were enrolled. Median age was 68 (ranging 48-79)years old. Median BMI was 25.6(ranging 21.9-31.4)kg/m 2. Median prostate specific antigen (PSA) was 23.5 (ranging 5.6-94.7)ng/ml. Median prostate volume was 37.6(ranging 16.2-127.9)ml. Median PSA density (PSAD) was 0.56(ranging 0.11-2.86)ng/ml 2. Fifteen cases were scored prostate imaging reporting and data system (PI-RADS) 4 and 16 cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 13.3 (ranging 4.6-36.7). All surgeries were successfully accomplished without open conversion. Median postoperative hospitalization time was 5 (ranging 4-7)d. No major complication occurred perioperatively. Recovery of urinary continence was within 6 months in all patients. According to the final pathological results, 1(3.2%) patient was confirmed with HGPIN. 30 (96.8%) patients were confirmed with adenocarcinoma, including 26 (86.7%) patients with CsPCa and 4(13.3%) patients with cisPCa. Among prostate cancer cases, the pathological stage of 11(36.7%) was T 2 and 19(63.3%) was T 3. Four(13.3%) cases were with ISUP grade 1, 7(23.3%) cases were with ISUP grade 2, 7(23.3%) cases were with ISUP grade 3 and 12 (40.0%) cases were with ISUP grade≥4.Two(6.7%) cases were in low risk group, 3(10.0%) cases were in intermediate risk group and 25 (83.3%) cases were in high risk group. Twelve(40.0%) patients had positive surgical margins. Standard pelvic lymph node dissection was carried out in 18 (17 prostate cancer and 1 HGPIN) cases. Sixty-two lymph nodes were dissected and none of them was positive. The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was 96.8%(30/31) in prostate cancer. Compared to low SUV max group, patients in high SUV max group had higher ISUP grade ( P=0.003) but there was no significant difference in positive surgical margin, seminal vesical invasion or pathological stage ( P>0.05). Among CsPCa patients, 10 (38.5%) cases were scored PI-RADS 4 and 16(61.5%) cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 14.3 (range 6.1-36.7). Compared to cisPCa and HGPIN patients, a smaller median prostate volume (34.3 vs. 73.0 ml, P=0.006), higher median PSAD (0.70 vs. 0.13 ng/ml 2, P=0.001), higher rates of PI-RADS 5 patients (61.5% vs. 0, P=0.018) and higher 68Ga-PSMA PET/CT SUV max (14.3 vs. 6.1, P=0.001) were found in CsPCa patients. Subgroup analysis showed no significant difference between SUV max and pathological stage (25.5 vs. 13.9), ISUP grades (15.4 vs. 14.4 vs. 14.0) and risk groups (9.7 vs. 14.9) in CsPCa patients ( P>0.05). Conclusions:The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT is high in prostate cancer. With efficient communication, radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by mpMRI and 68Ga-PSMA PET/CT is safe.
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Objective:To study the efficacy of 68Ga-PSMA PET/CT in evaluating lymph node metastases (LNMs) in patients with prostate cancer (PCa). Methods:Patients who recieved 68Ga-PSMA PET /CT examination in the First Affiliated Hospital of Air Force Military Medical University from July 2021 to February 2022 were enrolled. The patients’ age was (64.4±6.1) years old, with median total prostate specific antigen (tPSA) 34.5 (6.1-99.0) ng/ ml, including PSA<10ng/ ml in 12 cases, 10-20ng/ ml in 21 cases, and > 20 ng/ml in 25 cases. Preoperative clinical staging: 1 case in T 1 stage, 38 cases in T 2 stage, 16 cases in T 3stage, 3 cases in T 4 stage. Preoperative Gleason score of 10 cases was <7, 20 cases was 7, and 28 cases was > 7. According to D 'Amico risk grouping criteria, there were 8 cases in the low-risk group, 20 cases in the medium-risk group and 30 cases in the high-risk group. Preoperative examination of 68Ga-PSMA PET/CT showed no distant metastasis such as visceral metastasis and bone metastasis. All patients underwent radical prostatectomy and pelvic lymph node dissection. The following patients were excluded: patients received preoperative prostate surgery, patients received endocrine therapy, chemotherapy and radiotherapy for prostate cancer before surgery, a history of other malignant tumors in the past 2 years, biopsy pathological diagnosis of neuroendocrine cell prostate cancer and other special types of prostate cancer, prior history of major pelvic surgery, etc. Radical prostatectomy was performed. 38 patients received laparoscopic surgery and 20 patients received robot-assisted laparoscopic surgery. The sensitivity and specificity of 68Ga-PSMA PET /CT for the diagnosis of lymph node metastasis of prostate cancer were calculated according to the comparison of lymph node metastasis in postoperative pathological results and preoperative examination. Results:Postoperative pathological diagnosis: Gleason score of 9 cases was <7, 19 cases was 7, and 30 cases was >7. 37 cases were in pT 2 stage, 17 cases in pT 3 stage, and 4 cases in T 4 stage. There were 12 cases (20.7%) of positive resection margin, and 7 cases (12.1%) of lymphatic fistula. There were 10 patients with lymph node metastasis diagnosed by 68Ga-PSMA PET/CT before surgery, and 17 positive lymph node regions. A total of 11 patients were pathologically positive in lymph nodes, and a total of 20 lymph nodes regions were positive. Based on the number of patients, the specificity and sensitivity of 68Ga-PSMA PET /CT in diagnosing lymph node metastasis in patients were 97.9% (46/47) and 81.2% (9/11), respectively. Based on the number of regional lymph nodes, the specificity and sensitivity of 68Ga-PSMA PET /CT for regional lymph node diagnosis were 99.4%(326/328) and 75.0%(15/20), respectively. The specificity of lymph node metastasis in the external iliac group, the internal iliac group and the obturator group were 100.0%(114/114), 99.1%(110/111) and 98.1%(101/103), and the sensitivity was 100.0%(2/2), 60.00%(3/5) and 69.2%(9/13), respectively. Conclusion:68Ga-PSMA PET/CT can be used as a strong tool for precise guidance of PLND in PCa patients.
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Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.
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Objective:To investigate the value of 18F-PSMA PET/CT-derived prostate specific membrane antigen(PSMA)expression parameters, including maximum standardize uptake value(SUV max), PSMA receptor expressing tumor volume(PSMA-TV), and total lesion PSMA receptor expression(TL-PSMA), in predicting the risk of metastasis in elderly prostate cancer patients aged 60 years and older. Methods:Clinical data of 39 patients with prostate cancer diagnosed in our hospital from January 2019 to May 2021 and imaging data of 18F-PSMA PET/CT before treatment were analyzed retrospectively.PSMA-TV and TL-PSMA of primary tumor tissue were calculated from PET/CT images with 40% of the SUV max as the threshold value.The influence of 18F-PSMA PET/CT on clinical TNM staging was evaluated.The Mann-Whitney U test was used to compare the differences in values of various indicators between the groups with or without metastasis, including the total prostate-specific antigen(tPSA)level, Gleason score and PSMA expression parameters.The correlation of PSMA expression parameters with tPSA and Gleason score was analyzed.The area under the receiver operating characteristic(ROC)curve(AUC)was used to determine the predictive ability of different indicators for the risk of prostate cancer metastasis, and multivariate logistic regression analysis was used to screen for independent predictors of prostate cancer metastasis. Results:The Gleason score of 39 prostate cancer patients(median age: 67 years, age range: 60-83 years)was 7.0(7.0, 8.0), and the median prostate specific antigen(PSA)level was 14.83(7.37, 30.93)μg/L.There were 11 cases(28.2%)with metastasis(the metastasis group), and 28 cases(71.8%)without metastasis(the non-metastasis group). Based on PET/CT, the clinical N and M stages of five patients(12.8%)were changed, but two cases(5.1%)with pelvic lymph node metastasis were missed.The median ages of the metastasis group and the non-metastasis group were 63(60-79)years and 69(60-83)years, respectively, and the difference was not statistically significant( P=0.115). The metastasis group and the non-metastasis group had tPSA levels at 54.0(9.9, 75.8)μg/L and 10.2(6.8, 22.8)μg/L, the SUV max at 29.1(16.8, 35.3)and 7.7(6.0, 13.6), the PSMA-TV at 41.5(22.4, 90.9)cm 3 and 6.8(3.6, 9.3)cm 3, TL-PSMA at 279(139.7, 996.4)and 25.5(15.9, 37.0), Gleason scores at 8.0(7.0, 8.0)and 7.0(7.0, 8.0), respectively.There were statistically significant differences in tPSA( Z=-2.528, P=0.011), SUV max( Z=-4.151, P<0.001), PSMA-TV( Z=-3.995, P<0.001)and TL-PSMA( Z=-4.213, P<0.001)between the two groups.SUV max( r=0.537, P<0.01), PSMA-TV( r=0.496, P<0.01)and TL-PSMA( r=0.508, P<0.01)were all positively correlated with tPSA.Furthermore, SUV max( r=0.547, P<0.01), PSMA-TV( r=0.412, P<0.01)and TL-PSMA( r=0.433, P<0.01)were also positively correlated with Gleason score.ROC curve analysis showed that the AUCs of SUV max, PSMA-TV, TL-PSMA and tPSA in predicting prostate cancer metastasis were 0.932, 0.916, 0.938 and 0.763, respectively.Multivariate Logistic regression analysis showed that SUV max( OR=1.203, 95% CI: 1.001-1.445, P=0.049)was an independent predictor of prostate cancer metastasis. Conclusions:These PSMA expression parameters of 18F-PSMA PET/CT have a good value in predicting the risk of metastasis in elderly prostate cancer patients, and SUV maxmay serve as a potential molecular imaging indicator to independently predict prostate cancer metastasis.
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Objective:To compare the diagnostic values of different diagnostic criteria of prostate specific membrane antigen (PSMA) PET/CT for primary prostate cancer (PCa).Methods:From May 2019 to May 2021, 2-(3-(1-carboxy-5-((6- 18F-fluoro-pyridine-3-carbonyl)-amino)-pentyl)-ureido)-pentanedioic acid ( 18F-DCFPyL) PET/CT images of 78 patients (age: (68.5±1.4) years) with clinically suspected PCa in Shanxi Bethune Hospital were retrospectively collected and blind diagnosed by the three criteria of SUV max, PSMA reporting and data system (PSMA-RADS) score and molecular imaging PSMA (miPSMA) score. The diagnostic efficacy for PCa, the correlation between the diagnostic results and disease risk, and the consistency of the diagnostic results of the three criteria were compared. Delong test, Spearman rank correlation analysis, and intra-class correlation coefficient (ICC) were used to analyze data. Results:The sensitivities of SUV max, PSMA-RADS score and miPSMA score for PCa were all 93.75%(60/64) and the specificities were 12/14, 10/14 and 12/14 respectively; AUCs of the three criteria were 0.951, 0.862 and 0.951, with no significant difference between SUV max and miPSMA score ( z=0.00, P=1.000), while there were significant differences between PSMA-RADS score and SUV max or miPSMA score ( z values: 2.71, 2.93, P values: 0.007, 0.030). There were positive correlations between the diagnostic results of the three criteria and the disease risk (International Society of Urological Pathology (ISUP) grading: rs values: 0.66, 0.62, 0.63, all P<0.001; D′Amico grouping: rs values: 0.67, 0.64, 0.67, all P<0.001). The diagnostic results of the three criteria were highly consistent (ICC=0.941, 95% CI: 0.903-0.967). Conclusion:The SUV max and miPSMA score have higher diagnostic efficiency and correlation of disease risk, which are more suitable for clinical application.
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Prostate specific membrane antigen (PSMA) radioligand therapy (RLT) is effective in metastatic castration-resistant prostate cancer (mCRPC). However, PSMA RLT can cause radiation damage to salivary glands, especially 225Ac/ 177Lu-PSMA-617. Radiation-related salivary glands damage can cause xerostomia, reduce the quality of life, and even limit the dose of radiopharmaceuticals and reduce the efficacy of tumor treatment. At present, there are few literatures on PSMA RLT related salivary glands damage in China. In this article, radiation-related salivary glands damage and the related protective measures during 225Ac/ 177Lu-PSMA-617 RLT are reviewed based on domestic and foreign studies.
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Objective:To optimize the preparation conditions and methods of Al 18F-prostate specific membrane antigen (PSMA)-11 and evaluate the feasibility of clinical transformation. Methods:PSMA- N, N′-bis(2-hydroxy-5-(carboxyethy)benzyl)ethylenediamine- N, N′-diacetic acid (HBED-CC) dissolved in CH 3COONH 4 buffer (pH=4.8) was reacted with AlCl 3·3H 2O dissolved in pure water at a molar ratio of 1∶1 (60 ℃, 10 min), and then purified by tC18 column and freeze-dried to obtain [Al]-PSMA-11. [Al]-PSMA-11 was labeled by 18F - and the effects of reaction temperature and pH value on the labeling rate were investigated. The labeled products were purified by tC18 column and filtered through sterile filter to obtain Al 18F-PSMA-11. The comparison of biodistribution between Al 18F-PSMA-11 and 68Ga-PSMA-11 was analyzed on 5 healthy volunteers (age (56±8) years). The differences of SUV max between two groups were analyzed by independent-sample t test. Besides, the early and delayed imaging of Al 18F-PSMA-11 PET/CT were performed on a patient (70 years old) with recurrent prostate cancer for assessment of its potential for prostate cancer recurrence monitoring. Results:The labeling rate was (42.3±3.2)% reacting in aqueous phase (60 ℃, pH=4.8) for 15 min. After being purified with tC18 cartridge, the radiochemical purity of the product was still more than 95% after placement at room temperature for 3 h. Preliminary application demonstrated that there was no significant difference in the biodistribution of Al 18F-PSMA-11 and 68Ga-PSMA-11 among lacrimal gland, parotid gland, submandibular gland, liver, spleen, kidney, bladder and part of intestine and SUV max of targeted organs were also not different ( t values: 0.19-1.95, all P>0.05) between two groups. Multiple bone metastases were observed by Al 18F-PSMA-11 PET/CT delayed imaging (3 h) in a patient with recurrent prostate cancer. Conclusion:Al 18F-PSMA-11 produced with pre-conjugated [Al]-PSMA-11 meets the requirement of the PET imaging application, and it has good potential of localization and imaging for prostate cancer metastatic lesions.
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Objective:To investigate the preparation methods and quality control of 177Lu-labeled radiopharmaceuticals, and conduct preliminary clinical application research. Methods:177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-Phe1-Tyr3-octreotide (TOC) and 177Lu-prostate specific membrane antigen (PSMA)-I&T were labeled by manual labeling and automatic labeling, respectively. Factors such as the amount of precursor and nuclide, reaction temperature, pH value, reaction time, labeling yield and specific activity were investigated. Quality control of the products were carried out, such as clarity, pH value, sterility, bacterial endotoxin and stability in vitro. 177Lu-PSMA-I&T was applied to the treatment of prostate cancer patients, and the efficacy was evaluated by SPECT/CT imaging. Paired t test was used to analyze the data. Results:The amount of precursor and nuclide, reaction temperature, pH value and reaction time of the two methods were basically the same, both with high yield and specific activity. The yield of 177Lu-DOTA-TOC automatic labeling was significantly higher than that of manual labeling (99.2±0.4)% vs (95.3±1.5)% ( t=7.17, P<0.001), and the specific activity were (91.6±13.7) vs (89.1±13.2) GBq/μmol. The yield of 177Lu-PSMA-I&T automatic labeling was also significantly higher than that of manual labeling (99.6±0.3)% vs (95.7±1.3)% ( t=8.24, P<0.001), and the specific activity were (96.1±14.3) vs (93.2±13.8) GBq/μmol. The labeled products were colorless clear solution with pH value of 6.5-7.0. The sterility and bacterial endotoxin met the requirements. The radiochemical purity of the labeled products was more than 95% after 48 h, which showed good stability. The clinical application of 177Lu-PSMA-I&T in patients with prostate cancer showed that both primary and metastatic lesions had good uptake. Conclusions:The labeling of 177Lu radiopharmaceuticals is simple and has high yield and stability. The application of automatic labeling can simplify the process, improve the yield and reduce irradiation.
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Objective:To estimate the radiation dose (RD) to the public from patients undergoing 177Lu-prostate specific membrane antigen (PSMA)-617 therapy, and provide reference for the formulation of radiation protection measures. Methods:From July 2020 to January 2021, 10 patients with prostate cancer (age (71.1±5.9) years) who received 177Lu-PSMA-617 therapy in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. According to the different doses of 177Lu-PSMA-617, the patients were divided into the low-dose (5.55-6.29 GBq) group and high-dose (6.70-8.94 GBq) group. Respectively at 5, 30 min and 1, 2, 4, 24, 48, 72, 96, 144 h after intravenous injection of 177Lu-PSMA-617, whole-body initial dose-equivalent rate (DR) was measured with a radiation-survey meter at 0.3, 1.0 and 2.0 m from the patients. The statistics of ROI were analyzed by HERMES, and the corresponding equations were obtained by fitting the curve regression with double exponential function model. On the basis of human social contact model proposed by the National Council on Radiation Protection and Measurements (NCRP), the RD to the public from the patient discharged from the hospital at different times after completing the 177Lu-PSMA-617 injection was estimated. Results:All patients were discharged from the hospital at 72 h after treatment. The initial DR at 0.3, 1.0 and 2.0 m were (12.6±3.3), (4.7±1.2) and (1.6±0.4) μSv/h, respectively, and the RD to the co-sleeping partner, family members and colleagues who were in contact during the day were (999±253), (121±29) and (160±39) μSv, respectively. If the patients were discharged at 48 h after treatment, the RD to the adult family members could be controlled ≤5 mSv, and the RD to colleagues and children could be controlled ≤1 mSv. Starting from the injection of 177Lu-PSMA-617, the restriction duration for co-sleeping partner and colleagues were both 2 d and the restriction duration for children were 2 d (high-dose group) or 1 d (low-dose group). The patients needed to limit the time for public transportation from the 1st to 4th day after treatment, and there was no restriction from the 5th day. Conclusion:According to the current RD restrictions on the public, 177Lu-PSMA-617 is a relatively safe treatment modality for prostate cancer if good safety precautions are taken.
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Objective:Apt-A10-3.2 (aptamer of prostate specific membrane antigen (PSMA)) can be used as a specific ligand for early diagnosis and targeted treatment of prostate cancer. Mouse double minute 2 homolog (MDM2) is closely related to the malignancy of prostate cancer, and MDM2 small interfering RNA (siRNA) can silence MDM2 gene through RNA interference. To design a novel chimera of PSMA Apt-MDM2 siRNA and combine it with docetaxel (DTX) to explore a new diagnosis and treatment model combining targeted therapy of PSMA-positive prostate cancer with 99Tc m-chimera imaging monitoring. Methods:Apt-siRNA were obtained by covalent connection of PSMA Apt-A10-3.2 and MDM2 siRNA, which was combined with DTX to treat PSMA-positive prostate cancer cell lines (22RV1 and LNCaP). Cell lines were treated with Apt-siRNA alone or in combination with DTX. The levels of MDM2 and apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), poly ADP-ribose polymerase (PARP), caspase-3) were detected by Western blot, which were used to evaluate the therapeutic effect. Fifteen BALB/c mice bearing 22RV1 xenografts were treated with PBS, DTX+ Apt-siRNA (200 pmol) and DTX+ Apt-siRNA (400 pmol), respectively. Tumor volume and MDM2 level were observed, and 99Tc m-Apt-siRNA SPECT imaging was performed to obtain the tumor/muscle (T/M) ratio. One-way analysis of variance, Tukey′s test and linear regression analysis were used for data analysis. Results:The levels of MDM2 protein were significantly decreased by Apt-siRNA (0.25±0.02, F=183.40, P<0.001; 0.56±0.03, F=37.15, P<0.001) in 22RV1 and LNCaP cells. After the treatment of Apt-siRNA+ DTX, the levels of Bcl-2 were significantly decreased, and the levels of Bax, PARP and caspase-3 were significantly increased. MDM2 protein level (400 pmol: 0.59±0.12; F=49.99, P=0.023) and tumor volume (400 pmol: (0.22±0.07) cm 3;F=71.30, P=0.039) were significantly inhibited by Apt-siRNA+ DTX in mice bearing 22RV1 xenografts. As for 99Tc m-Apt-siRNA SPECT imaging in vivo, T/M ratio of treatment group was significantly decreased (400 pmol: 2.07±0.22; F=34.99, P=0.022), and there was a linear regression relationship between T/M ratio and the expression level of MDM2 ( R2=0.875, P<0.001). Conclusion:Apt-siRNA combined with DTX can effectively inhibit the progression of prostate cancer, and realize visual targeted diagnosis and treatment of PSMA-positive prostate cancer by coupling radionuclide technetium.
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Objective:To compare the effect of different β values on the semi-quantitative accuracy and image quality of 68Ga-prostate specific membrane antigen (PSMA) PET/CT imaging after partial volume effect correction (PVC). Methods:In the model experiment, image reconstruction was carried out based on block sequential regularized expectation maximization algorithm (BSREMA) with the range of β values from 100 to 1 000. Recovery coefficient (RC), contrast recovery (CR) and background variability (BV) were measured to evaluate semi-quantitative accuracy and image quality. In the clinical study, image data of 21 prostate cancer patients (age 45-78 years) who underwent 68Ga-PSMA PET/CT examination in the First Hospital of Shanxi Medical University from March 2019 to February 2020 were retrospectively collected. A total of 29 abdominal imaging positive lymph nodes were divided into the small lymph node group (diameter <10 mm; n=12) and the large lymph node group (10 mm≤diameter≤30 mm; n=17). SUV parameters including SUV max, SUV mean and peak of SUV (SUV peak) and the influence of different β values on the SUV parameters were evaluated. The signal to noise ratio (SNR) and subjective scores were used to evaluate image quality. Independent-sample t test, Kappa test and Pearson correlation analysis were used to analyze data. Results:The model experiment showed that CR, RC and BV decreased with the increase of β values. The image quality, image clarity, lesion significance, and total image scores given by nuclear medicine physicians showed strong consistency ( Kappa values: 0.65-0.87, P values: 0.026-0.043). The small lymph node group had the highest score (13 and 14) with β value of 600, while the large lymph node group had the highest score (13 and 14) with β value of 700. SNR of the two groups increased steadily within β values from 100 to 600 ( t values: 2.49-8.99, P values: 0.023-0.038). When the β value was higher than 600, SNR of the small lymph node group reached a plateau ( t values: 1.28-2.00, P values: 0.072-0.098), while the SNR of the large lymph node group continued to increase ( t values: 2.98-4.63, P values: 0.012-0.029). Before PVC, there were significant negative correlations between SUV parameters and β values ( r values: from -0.94 to -0.64, P values: 0.039-0.046). After PVC, it was found that SUV mean and SUV max still had significant negative correlation with β values ( r values: from -0.78 to -0.68, P values: 0.035-0.042), while the SUV peak showed no significant correlation with β values ( r values: -0.22, -0.28, P values: 0.069, 0.126). Conclusions:Based on subjective scores and semi-quantitative indicators, 68Ga-PSMA PET/CT is superior to select β values of 600 and 700 for image reconstruction based on BSREMA. The SUV peak of small lesions is stable after PVC and the clinical value should be explored in further.
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Prostate cancer is the most common malignant tumor in male urinary system, and the morbidity and mortality rate are increasing year by year. Traditional imaging examinations have some limitations in the diagnosis of prostate cancer, and the advent of molecular imaging probes and imaging technology have provided new ideas for the integration of diagnosis and treatment of prostate cancer. In recent years, prostate-specific membrane antigen (PSMA) has attracted much attention as a target for imaging and treatment of prostate cancer. PSMA ligand positron emission tomography (PET) has important reference value in the diagnosis, initial staging, detection of biochemical recurrence and metastasis, clinical decision-making guidance and efficacy evaluation of prostate cancer. This article briefly reviews the clinical research and application progress on PSMA ligand PET imaging in prostate cancer in recent years, so as to raise the efficiency of clinical applications.