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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 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 diagnostic performance of repeat biopsy 68Ga-PSMA PET/CT to distinguish between benign and malignant prostate disease. Methods:The clinical data and medical imaging of thirty-nine patients underwent repeat prostate biopsy were analyzed respectively in this study. The median age of patients was 65 years (range 46-81 years), the median PSA level was 11.0ng/ml (range 5.4-49.8 ng/ml), f/tPSA was 0.15(0.01-16.50)ng/ml, prostate volume was 43.80(7.79-108.63)ml, and PSA density was 0.24(0.09-2.31)ng/ml 2. All patients underwent pre-biopsy 68Ga-PSMA PET/CT and the standard transrectal ultrasound-guided systematic prostate biopsy. Based on the biopsy results, 68Ga-PSMA PET/CT images of all patients were visually and semi-quantitatively analyzed. By visual analysis, 68Ga-PSMA uptake in prostate was defined as focal, multimodal and inhomogeneous, and then the detection rate of prostate cancer in each subgroup was analyzed. The value of the ROC curve in the diagnosis of prostate cancer was analyzed based on the SUV max of prostate cancer(SUV max), tumor-to-normal-prostate background(SUV T/BGp)as semi-quantitative parameters of 68Ga-PSMA PET/CT. Results:Prostate cancer was detected in 18 patients (46.2%) and 12 patients (30.8%) had clinically significant disease. There were 11, 5 and 2 patients with prostate cancer respectively in men with a focal (12 patients), multifocal(7 patients) and inhomogeneous (20 patients) 68Ga-PSMA uptake. The ROC analysis revealed a SUV max 5.3 and SUV T/BGp1.8 as an optimal cut-off level to distinguish between non-prostate cancer and prostate cancer in 68Ga-PSMA PET/CT, the sensitivity and specificity were 100.0% and 85.7% for SUV max (AUC=0.979), 83.3% and 90.5% for SUV T/BGp (AUC=0.915). Conclusions:Pre-biopsy 68Ga-PSMA PET/CT could help to distinguish between benign and malignant prostate disease before repeat prostate biopsy and detect the foci of prostate cancer.
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Objective@#To investigate the relationship between SUVmax on preoperative 68Ga-PSMA PET-CT and the clinicopathological characteristics of patients treated with radical prostatectomy.@*Methods@#The clinicopahtological data of patients evaluated with 68Ga-PSMA PET-CT preoperatively and treated with radical prostatectomy between May 2016 and August 2019 were retrospectively reviewed. 31 patients with a mean age (63.1±4.9) and baseline PSA (72.71±173.15)ng/ml were enrolled. Their BMI mean (24.6±3.0)kg/m2. Baseline testosterone of 14 patients was (4.72±1.64)ng/ml.Based on the Gleason scores related ISUP classification, all patients were classified into grade one in 5 cases, grade 2in 7 cases, grade 3 in 4 cases, grade 4 in 10 cases and grade 5 in 5 cases. The clinical classification included 6 cases in T2a stage, 2 cases in T2b stage, 17 cases in T2c stage, 1 case in T3a stage, 4 cases in T3b stage and 1 case in T4 stage. SUVmax was accessed by two independent professional nuclear medicine physicians. SUVmax was 12.49±9.38. SPSS 16.0 software was used to do statistic analysis.@*Results@#The post-operative pathological results showed the surgical margin positive in 19 cases, negative in 12 cases, vascular positive in 5 cases, negative in 20 case, positive nerve invasion in 20 cases and negative in 11 cases. 2 patients were low risk, 7 patients were medium risk and 22 patients were high risk according to D′Amico classification. Based on the basis of PSA(≤10 or>10) and Gleason score(≤6 or>6), 6 patients were in group with low PSA and low Gleason score, 5 patients were low PSA and high Gleason score, 9 patients were high PSA and low Gleason score, 11 patients were high PSA and high Gleason score. SUVmax had a significant positive relationship with pathological ISUP(r=0.434, P=0.015) and SUVmax in patients with positive intravascular tumor emboli was significantly higher than those with negative intravascular tumor emboli(14.78±10.68 vs. 8.17±2.81, P=0.005). No significant correlation was found between SUVmax and baseline PSA, testosterone, pathologic T stage, surgical margin, nerve invasion, pelvic lymph node status as well as risk stratification. SUVmax could distinguish pathologic ISUP grade 5 with a maximum AUC 0.747 (P=0.033) and the sensitivity was 88.9%. The specificity was 77.3% when SUVmax≥11.34. SUVmax in patients with upgrading ISUP was significantly higher than that in patients with downgrading ISUP (16.01±5.40 vs. 4.98±2.11, P=0.007).@*Conclusions@#SUVmax measured on preoperative 68Ga-PSMA PET-CT may have a clinical significance in predicting unfavorable pathological factors for patients treated with radical prostatectomy.
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Objective:To produce the solid target nuclide 89Zr , and prepare the probe 89Zr-desferrioxamine (DFO)-Trastuzumab. Methods:The 89Y(p, n) 89Zr nuclear reaction was used for 89Zr production. 89Y target was irradiated by 20 μA proton in a medical cyclotron ( E=12.5 MeV) for about 1-2 h. 89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution. The characteristic peak, radionuclide purity and radiochemical purity of 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature, and the radiochemical purity was measured. Results:89Zr was prepared successfully for 11 times, and the production of 89Zr was 555-1 506 MBq, with production rate of (34.8±5.2) MBq·μA -1·h -1. After the purification (purification rate: 42%-87%), 227.2-991.6 MBq 89Zr was obtained, with the concentration of 1.0×10 6 MBq/L. The γ spectrum showed that the characteristic peak of 89Zr were 511 and 909 keV, and no impurities were found. The radionuclide purity and radiochemical purity were both close to 100%. 89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%, and it was above 90% within 72 h in human serum albumin (HSA) solution. Conclusion:Through the self-designed target assembling, the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved, which provides guarantee for the clinical application of the 89Zr drug.
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Objective To investigate the relationship between SUVmax on preoperative 68Ga-PSMA PET-CT and the clinicopathological characteristics of patients treated with radical prostatectomy.Methods The clinicopahtological data of patients evaluated with 68Ga-PSMA PET-CT preoperatively and treated with radical prostatectomy between May 2016 and August 2019 were retrospectively reviewed.31 patients with a mean age (63.1 ± 4.9) and baseline PSA (72.71 ± 173.15) ng/ml were enrolled.Their BMI mean (24.6 ± 3.0) kg/m2.Baseline testosterone of 14 patients was (4.72 ± 1.64) ng/ml.Based on the Gleason scores related ISUP classification,all patients were classified into grade one in 5 cases,grade 2in 7 cases,grade 3 in 4 cases,grade 4 in 10 cases and grade 5 in 5 cases.The clinical classification included 6 cases in T2a stage,2 cases in T2b stage,17 cases in T2c stage,1 case in T3a stage,4 cases in T3b stage and 1 case in T4 stage.SUVmax was accessed by two independent professional nuclear medicine physicians.SUVmax was 12.49 ± 9.38.SPSS 16.0 software was used to do statistic analysis.Results The post-operative pathological results showed the surgical margin positive in 19 cases,negative in 12 cases,vascular positive in 5 cases,negative in 20 case,positive nerve invasion in 20 cases and negative in 11 cases.2 patients were low risk,7 patients were medium risk and 22 patients were high risk according to D'Amico classification.Based on the basis of PSA(≤ 10 or > 10) and Gleason score (≤6 or > 6),6 patients were in group with low PSA and low Gleason score,5 patients were low PSA and high Gleason score,9 patients were high PSA and low Gleason score,11 patients were high PSA and high Gleason score.SUVmax had a significant positive relationship with pathological ISUP (r =0.434,P =0.015) and SUVmax in patients with positive intravascular tumor emboli was significantly higher than those with negative intravascular tumor emboli (14.78 ± 10.68 vs.8.17 ± 2.81,P =0.005).No significant correlation was found between SUVmax and baseline PSA,testosterone,pathologic T stage,surgical margin,nerve invasion,pelvic lymph node status as well as risk stratification.SUVmax could distinguish pathologic ISUP grade 5 with a maximum AUC 0.747 (P =0.033) and the sensitivity was 88.9%.The specificity was 77.3% when SUVmax ≥ 11.34.SUVmax in patients with upgrading ISUP was significantly higher than that in patients with downgrading ISUP (16.01 ± 5.40 vs.4.98 ± 2.11,P =0.007).Conclusions SUVmax measured on preoperative 68 Ga-PSMA PET-CT may have a clinical significance in predicting unfavorable pathological factors for patients treated with radical prostatectomy.
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Objective To investigate the value of 68Ga-prostate specific membrane antigen (PSMA)-617 PET/CT in predicting high-risk prostate cancer.Methods From May 2016 to January 2017,30 patients (median age 67 years) with biopsy-proven prostate cancer were included.The 68Ga-PSMA-617 PET/CT images and clinical data of all patients were analyzed retrospectively.According to prostate cancer risk stratification criteria of National Comprehensive Cancer Network (NCCN) Guidelines (including Gleason scores,prostate specific antigen (PSA)),all patients were classified into low-moderate-risk group and high-riak group.PET images were analyzed semi-quantitatively and maximum standardized uptake value (SUVmax) of primary prostate cancer was measured.SUVmax of 68Ga-PSMA-617 PET/CT was used to establish logistic regression model for predicting high-risk prostate cancer,and the diagnostic efficiency of the model was evaluated by receiver operating characteristic (ROC) curve analysis.Results The median Gleason score of 30 patients was 7.5 (7,9),and the median PSA was 34.0 (19.4,119.1) μg/L,including 9 patients with PSA≤ 20 μg/L and 21 patients with PSA>20 μg/L.According to the NCCN Guidelines,there were 24 patients with high-risk prostate cancer and 6 patients with low-moderate-risk prostate cancer.SUVmax was higher in high-risk group than that in low-moderate-risk group (14.2 (11.4,23.1) vs 7.9 (3.8,13.1);u =118,P< 0.05).Logistic regression model established with SUVmax could effectively predict high-risk prostate cancer with the area under ROC curve of 0.819.When the cut-off value was set as 0.73,the sensitivity and specificity of the model were 87.5%(21/24) and 4/6 respectively.Conclusion SUVmax of 68Ga-PSMA-617 PET/CT can be used as an imaging biomarker for predicting high-risk prostate cancer.
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Objective To prepare a novel somatostatin receptor (SSTR) antagonist 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-JR11 (Cpa-c(D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2 ) tracer and observe its biodistribution and microPET imaging in mice. Methods One ml HCl (0.05 mol/L) containing 68GaCl3(148 MBq) was added into 65μl NaAc (1 mol/L) and 4μg NOTA-JR11. The mixture reacted at 95 ℃ for 15 min, and then was purified with Sep-Pak? C18 Light column to obtain 68 Ga-NOTA-JR11. 68 Ga-NOTA-JR11 was subjected to quality control analysis including radiochemical purity and in vitro stability by radio-high performance liquid chromatography. Biodistribution of 68Ga-NOTA-JR11 (0.37 MBq) in BALB/c mice (n=9) at 5, 30, 60 min postinjection were observed (n=3 for each time point), and the percentage activity of injection dose per gram of tissue (%ID/g) was calculated. 68Ga-NOTA-JR11 (14.8 MBq) microPET imaging of BALB/c mice (n=1) at 60 min postinjection was observed. Results 68 Ga-NOTA-JR11 was obtained successfully within 15 min, with yielding rate of 90%, radiochemical purity of more than 99%, and specific activity of 6. 10 GBq/μmol. The tracer showed excellent stability ( radio-chemical purity:95%) in different buffers within 150 min. The biodistribution was basically consistent with microPET imaging results. 68 Ga-NOTA-JR11 was metabolized through the kidneys and had low uptake in the liver ((0.75±0.26) %ID/g) at 60 min postinjection. Conclusions 68 Ga-NOTA-JR11 can be prepared rapidly, with high yielding rate and radiochemical purity. Biodistribution and imaging results provide basic information for the further study of somatostatin receptor imaging in neuroendocrine tumors.
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Immunosuppressant targeting programmed death protein-1 and its ligand (PD-1/PD-L1) is a hot topic in solid tumor immunotherapy.Detection of PD-1/PD-L1 expression in solid tumor patients by molecular imaging can predict whether tumor patients can benefit from immunotherapy.Small molecular polypeptide inhibitors have the advantages of low molecular weight,fast diffusion in tumor microenvironment,uniform distribution and easy access to the deep part of solid tumor.Non-invasive,real-time and quantitative detection of PD-1/PD-L1 expression in tumor patients can be performed by radionuclide labeled small molecular polypeptide inhibitor molecular probe PET imaging.It is expected to provide new detection methods for patient screening,efficacy monitoring,treatment plan optimization and prognosis evaluation.
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Objective@#To optimize the radiolabeling of prostate specific membrane antigen (PSMA)-targeted probe Al18F-PSMA-BCH (Beijing Cancer Hospital) and to evaluate its potential for clinical trial and translation.@*Methods@#The mixture of PSMA-BCH, AlCl3, potassium biphthalate and no-carrier loaded 18F- was reacted at 110 ℃ for 15 min, then purified by Sep-Pak Light C18 column and filtered through 0.22 μm sterile filter to obtain Al18F-PSMA-BCH. The radiolabeled yield and radiochemical purity were determined. Al18F-PSMA-BCH PET/CT imaging was performed on 5 healthy volunteers (age: (68±7) years) for biodistribution and radiation dosimetry estimate and on 1 patient (65 years) with recurrent prostate cancer.@*Results@#The non-decay-corrected radiochemical yield of Al18F-PSMA-BCH was (38.0±3.5)% with the radiochemical purity >99% and the specific activity of (16.4±4.4) MBq/nmol. Al18F-PSMA-BCH was stable in saline at room temperature. In healthy volunteers, radioactivity was mainly accumulated in the bladder, kidneys, lacrimal glands, parotid glands and submandibular glands, of which kidneys were the most critical organs with the dosimetry of (152.89±33.43) μGy/MBq, while bones showed lower uptake ((11.10±1.23) μGy/MBq) than most organs. The effective dose of whole body was (0.013 5 ±0.002 5) mSv/MBq. Multiple bone metastases were observed by Al18F-PSMA-BCH PET/CT imaging in a patient with recurrent prostate cancer.@*Conclusions@#Al18F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis, staging and monitoring recurrence of prostate cancer.
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Objective To optimize the radiolabeling of prostate specific membrane antigen (PSMA)-targeted probe Al18 F-PSMA-BCH (Beijing Cancer Hospital) and to evaluate its potential for clinical trial and translation. Methods The mixture of PSMA-BCH, AlCl3 , potassium biphthalate and no-carrier loaded 18F- was reacted at 110 ℃ for 15 min, then purified by Sep-Pak Light C18 column and filtered through 0.22 μm sterile filter to obtain Al18 F-PSMA-BCH. The radiolabeled yield and radiochemical purity were determined. Al18 F-PSMA-BCH PET/ CT imaging was performed on 5 healthy volunteers (age: (68±7) years) for bio-distribution and radiation dosimetry estimate and on 1 patient (65 years) with recurrent prostate cancer. Re-sults The non-decay-corrected radiochemical yield of Al18F-PSMA-BCH was (38. 0±3.5)% with the radiochem-ical purity >99% and the specific activity of (16.4±4.4) MBq/ nmol. Al18 F-PSMA-BCH was stable in saline at room temperature. In healthy volunteers, radioactivity was mainly accumulated in the bladder, kidneys, lacrimal glands, parotid glands and submandibular glands, of which kidneys were the most critical organs with the dosim-etry of (152.89±33.43) μGy/ MBq, while bones showed lower uptake ((11.10±1.23) μGy/ MBq) than most or-gans. The effective dose of whole body was (0.0135 ±0.0025) mSv/ MBq. Multiple bone metastases were ob-served by Al18F-PSMA-BCH PET/ CT imaging in a patient with recurrent prostate cancer. Conclusions Al18 F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis, staging and monitoring recurrence of prostate cancer.
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Objective To briefly retrospect the production and quality control of 64 Cu(n = 9) in Department of Nuclear Medicine of Peking University Cancer Hospital in order to provide useful information for the further production and application of this novel radionuclide. Methods 64 Ni(p, n) 64 Cu nuclide re-action was used for the 64 Cu production. Firstly, a new electro-planting device for 64 Ni planting was de-signed. HM-20 cyclotron was applied to irradiate the slice for 5-8 h. 64 CuCl2 was purified, collected and in-jected into normal mice. MicroPET was conducted to monitor the metabolism in vivo. Results A new type of electro-planting device was designed and assembled. The enriched 64 Ni target showed smooth, even, dense surface and without obvious pits and cracks. High specific 64 Cu (1.3-4.1 GBq) can be collected after radio-chemical purification. 64 Cu was finally dissolved in 0.01 mol/ L HCl with high radionuclide purity (over 99.97%). MicroPET of 64 CuCl2 in normal mice showed that the radioactivity was mainly accumulated in the liver. Conclusion A new and real-time observable device for 64 Ni electro-plating has been designed and successfully used in the production of 64 Cu with high specific activity.