| Project ⅠPart ⅠAl18F-PSMA-617 PET/CT Dynamic Imaging for Characterization of Primary Prostate CancerObjective:Al18F-PSMA-617 is a novel agent based on prostate specific membrane antigen(PSMA).The aims of this study were to investigate the pharmacokinetics of Al18F-PSMA-617 and to explore a clinically applicable imaging protocol.Methods:26 biopsy-confirmed,treatment-na?ve prostate cancer patients were included.All patients underwent an early dynamic imaging of the prostate bed for 60 minutes,followed by static scans at 2 and 4 hours post-injection.The differences in lesion detectability at different time point were compared.SUVmax,time-activity curves,quantitative analysis based on a 2-tissue compartment model and Patlak analysis were compared between prostate cancer and normal prostate tissue.Results:(1).Tumor detection:25/26 patients showed at least one PSMA positive lesion on dynamic imaging and delayed imaging(2hp.i,and 4h p.i),only 1 patient showed no PSMA positive lesion on multi time-point imaging.Lesion-based analysis showed delayed imaging at 4h p.i revealed more intraprostatic lesions than dynamic imaging and static imaging at 2h p.i,but there was no difference in detecting metastatic lesions(intraprostatic lesions:42 vs.33 vs.33;metastatic lesions:17 vs.17 vs.17).(2).Tracer uptake over time:tracer uptake in PCa was increased over time.Also,the tumor-to-prostate ratio improved over time(the mean TPR at 60 min,2h and 4h p.i were 3.18,4.77,and 6.41,respectively;p<0.001).Both the influx rate(Ki:0.11±0.11 vs.0.03±0.02,p<0.0001)and SUVmax(4h p.i.:19.23±15.28 vs.2.61±0.52,p<0.0001)in PCa was also significantly higher than in normal prostate tissue.Conclusion:Multi time-point imaging showed that static imaging at 4h p.i detected more intraprostatic lesions than imaging within 2h p.i.The tumor-to-prostate ratio improves over time,suggesting delayed imaging at 4h p.i.for optimal visualization of prostate cancer.Part ⅡComparison of the detection efficiencies of Al18F-PSMA-617 and 68Ga-PSMA-61 7 PET/CT in patients with prostate cancerObjective:The aims of this study was to head-to-head compare the detection efficiency of Al18F-PSMA-617 with 68Ga-PSMA-617 PET/CT in the setting of newly diagnosed intermediate-or high-risk PCa.Methods:79 patients with biopsy-confirmed prostate cancer underwent Al18F-PSMA-617 and 68Ga-PSMA-617 PET/CT within 7 days.PET findings were head-to-head compared using pathologic examination of whole-mount slices or biopsy specimens as gold-standard.The Cohen κ-coefficient was used to assess the concordance between Al18F-PSMA-617 and 68Ga-PSMA-617 for detecting intraprostatic lesions.The SUVmax was measured for all lesions and tumor-to-prostate SUVmax ratio(TPR)was calculated.Patient-and lesion-based detection rate,SUVmax,and TPR were compared between 68Ga-PSMA-617 and Al18F-PSMA-617.Sensitivity,specificity,positive predictive value,and negative predictive value for diagnosing csPCa were reported for each radiotracer.And finally,areas under receiver-operating-characteristic curves(ROC)were calculated for discriminating clinically significant PCa(csPCa)from insignificant ones,and best-fit SUV and TPR cutoffs were calculated using the Youden index for each radiotracer.Results:1.Comparison of Al18F-PSMA-617 and 68Ga-PSMA-617 PET/CT images:(1)Al18F-PSMA-617 PET and 68Ga-PSMA-617 PET revealed 116 and 103 PSMA-positive intraprostatic lesions.The dominant intraprostatic lesions were similarly detected by both radiotracers in 74 patients with a κ value of 0.737(p<0.001).(2)Patient-based detection rate of PCa was significantly higher for Al18F-PSMA-617 than 68Ga-PSMA-617(94.9%vs.93.7%,p<0.001).(3)There were 18 patients had metastatic diseases,among which Al18F-PSMA-617 and 68Ga-PSMA-617 were similarly positive in 14 patients.Per-patient level sensitivity,specificity,PPV,and NPV for detecting metastatic diseases for both tracers were 77.8%,100%,100%,and 92.7%,respectively.2.Using surgical pathology results as a reference:(1)Qualitative analysis:41 patients received radical prostatectomy and pathological examination totally identified 76 prostate cancer foci.Lesion-based detection rate of PCa was higher for Al18F-PSMA-617 than 68Ga-PSMA-617(75%vs.68.4%,p<0.01).As for detection of csPCa,lesion-based analysis achieved a sensitivity of 86.8%,a specificity of 48%,a PPV of 78.0%,and a NPV of 63.2%for Al18F-PSMA-617,while for 68Ga-PSMA-617,the corresponding results were 83.0%,60.0%,81.5%,and 62.5%,respectively.(2)Quantitative analysis:According to ROC curve analysis,the optimal cut-off values of 18F-SUVmax,18F-TPR,68Ga-SUVmax and 68Ga-TPR for identifying csPCa were 4.81,1.91,4.37,and 2.28,respectively,and the areas under the operating curve(AUC)were 0.84,0.85,0.86 and 0.78,respectively.3.Analysis of PET semi-parameters:there was a strong positive correlation of tracer uptake in matched lesions between the 2 radiotracers(r=0.9109,p<0.0001),but Al18F-PSMA-617 PET exhibited significantly higher SUVmax than 68Ga-PSMA-617 PET both in intraprostatic(18.62±17.80 vs.14.79± 12.12,p<0.0001)and metastatic lesions(11.55±9.94 vs.9.68±7.94,p=0.0044),and the TPR in intraprostatic lesions for Al18F-PSMA-617 was also higher than that for 68Ga-PSMA-617(6.06±4.97 vs.5.15±4.55,p=0.0004).SUVmax of the intraprostatic lesions for Al18F-PSMA-617 was moderate positive correlation with PSA level(r=0.449,p<0.0001)and postprostatectomy ISUP grade group(r=0.547,p=0.0084).Conclusion:Al18F-PSMA-617 exhibited higher tumor uptake and better detectability in intraprostatic tumor than 68Ga-PSMA-617 PET/CT,which suggest that Al18F-PSMA-617 may be more suitable in the setting of detecting primary PCa.Project ⅡPSMA and 18F-FDG PET imaging for the Treatment of Metastatic Prostate Cancer with 223Ra:Initial application and experienceObjective:Imaging plays a vital role in screening patients with metastatic prostate cancer for radium-223 dichloride(223Ra)treatment of bone metastases.The purpose of this study was to share our experience of the use of prostate specific membrane antigen(PSMA)and/or 18F-fluoroodexyglucose(18F-FDG)positron emission tomography(PET)in the setting of radium-223 in treatment of bone metastases of prostate cancer.Methods:Imaging data of 11 consecutive PCa patients who were scheduled to undergo 223Ra treatment for bone metastases at Peking Union Medical College Hospital between September 2021 to January 2023 were retrospectively analyzed.Comparison was performed between baseline PET/CT images and bone scintigraphy,and we also evaluated the value of different modalities in efficacy evaluation.Results:(1)In 2 patients PET revealed visceral metastases,which changed the therapeutic decision.9 patients(8 metastatic castration resistant prostate cancer patients and 1 metastatic hormone-sensitive prostate cancer patient)were enrolled and totally received 36 injections of 223Ra,the corresponding number of patients received 6,5,4,2,and 1 injection were 3,1,2,2,and 1,respectively.(2)At baseline,3 patients were classified as a match pattern between PET and bone scintigraphy,among whom 1 patient had a partial remission disease(completed 6 injections),1 had a stabled disease(completed 6 injections),and the remaining 1 had experienced disease progression(died of heart failure after 5 injections).PET revealed more bone involvements than bone scintigraphy in 6 patients,which caused a mismatch pattern between PET and bone scintigraphy,among whom 5/6 patients had experienced disease progression,except 1 changed to endocrine therapy after receiving 1 injection of 223Ra treatment with no evaluation conducted.(3)5 patients additionally received both bone scintigraphy and PET/CT scans after 3 or 6 injections of 223Ra for evaluating therapeutic response.3 patients had similarly therapeutic response according to bone scintigraphy and PET/CT,and in the remaining 2,according to bone scintigraphy,both showed stable disease.While according to PET/CT,1 showed progressive disease and the other showed partial response.Conclusion:PSMA PET and/or 18F-FDG PET could help detect visceral metastases and assist in patient screening.A mismatch pattern between baseline PET images and bone scintigraphy suggests a worse outcome of 223Ra treatment.During the efficacy evaluation process,PSMA and/or 18F-FDG PET(especially PSMA PET)also outperform to bone scan. |
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