scholarly journals 68Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry and First Comparison with 68Ga-PSMA-11 in Prostate Cancer

Author(s):  
Jiaying Zhang ◽  
Zefang Lin ◽  
Xiaojun Zhang ◽  
Rong Lin ◽  
Mengchao Cui ◽  
...  

Abstract PurposeThis prospective trial aimed to evaluate the safety, dosimetry, biodistribution, and diagnostic efficacy of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first comparison with 68Ga-PSMA-11 in prostate cancer (PCa) patients.MethodsFive healthy volunteers and ten PCa patients with a previous clinical 68Ga-PSMA-11 PET/CT were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA with a dose of 1.85MBq/kg. Healthy volunteers received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan, whole-body PET was performed with 2 min per bed position in 40 min post-injection. In addition, 68Ga-PSMA-11 scanning was performed on PCa patients within 10 days under the same acquisition procedure. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake (SUVmax) were measured. A lesion-by-lesion analysis was performed.Results68Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 uSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 uSv/MBq) in accordance with the expected PSMA renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 μSv/MBq. The SUVmax of 68Ga-PSMA-11 and 68Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases were 11.2 ± 10.76 vs. 4.41 ± 2.72, 7.6 ± 1.58 vs. 2.95 ± 1.11 and 4.86 ± 1.94 vs. 3.26 ± 1.2, respectively.ConclusionInjection of 68Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. Compared to 68Ga-PSMA-11, 68Ga-DOTA-DiPSMA shows comparable pharmacokinetics and detection ability in PCa patients that warrant further head-to-head comparison. Low non-specific uptake in salivary glands and kidneys of 68Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with 177Lu, 90Y, or 225Ac.

2020 ◽  
Author(s):  
Chunxia Qin ◽  
Yongkang Gai ◽  
Qingyao Liu ◽  
Weiwei Ruan ◽  
Fang Liu ◽  
...  

Abstract Purpose To analyze 68Ga-PSMA-617 PET/CT or PET/MR and delayed PET/MR images in patients diagnosed with or suspected of prostate cancer, and to explore the optimal use of PET/CT and PET/MR for initial diagnosis and staging in prostate diseases.Methods Images from conventional scan by 68Ga-PSMA whole-body PET/CT or PET/MR followed by delayed pelvic PET/MR were retrospectively analyzed. Prostatic 68Ga-PSMA uptake was measured as SUVmax1 (conventional scan 1 h post injection) and SUVmax2 (delayed scan 3 h post injection). Age, PSA levels, and SUVmax were compared between benign and malignant cases. The correlation of SUVmax1 and SUVmax 2 was analyzed. Diagnostic performance was evaluated by ROC analysis.Results We enrolled 56 patients with 41 malignant and 15 benign prostate lesions. Fifty-three patients had paired conventional and delayed scans. Age, PSA levels, and SUVmax were significantly different between benign and malignant cases. A good correlation was found between SUVmax1 and SUVmax2. There was significant difference between SUVmax1 and SUVmax2 in the malignant group (p = 0.001). SUVmax1 had superior diagnostic performance than SUVmax2, SUVmax difference and PSA levels, with a sensitivity of 85.4%, a specificity of 100% and an AUC of 0.956. A combination of SUVmax1 with nodal and/or distant metastases and MR PIRADS V2 score had a sensitivity and specificity of 100%. Delayed pelvic PET/MR imaging in 33 patients were found to be redundant because these patients had nodal and/or distant metastases which can be easily detected by PET/CT.Conclusion Combined 68Ga-PSMA whole-body PET/CT and pelvic PET/MR can accurately differentiate benign prostate diseases from prostate cancer and accurately stage prostate cancer. Whole-body PET/CT is sufficient for advanced prostate cancer, and more economic and time-saving than PET/MR. Pelvic PET/MR contributes to diagnosis and accurate staging in early prostate cancer. Imaging at about 1 hour after injection is sufficient in most patients.Trial registration: NCT03756077. Registered 27 November 2018 - Retrospectively registered, https://clinicaltrials.gov/show/NCT03756077


2021 ◽  
Vol 8 ◽  
Author(s):  
Chunxia Qin ◽  
Yongkang Gai ◽  
Qingyao Liu ◽  
Weiwei Ruan ◽  
Fang Liu ◽  
...  

Purpose: To analyze 68Ga-PSMA-617 PET/CT or PET/MR and delayed PET/MR images in patients diagnosed with or suspicion of prostate cancer, and to explore the optimal use of PET/CT and PET/MR for initial diagnosis and staging in prostate cancer.Methods: Images from conventional scan by 68Ga-PSMA whole-body PET/CT or PET/MR followed by delayed pelvic PET/MR were retrospectively analyzed. Prostatic 68Ga-PSMA uptake was measured as SUVmax1 (conventional scan 1 h post injection) and SUVmax2 (delayed scan 3 h post injection). Age, PSA levels, and SUVmax were compared between benign and malignant cases. The correlation of SUVmax1 and SUVmax2 was analyzed. Diagnostic performance was evaluated by ROC analysis.Results: Fifty-six patients with 41 prostate cancers and 15 benign prostate lesions were enrolled. Fifty-three patients had paired conventional and delayed scans. Age, tPSA, fPSA levels, and SUVmax were significantly different between benign and malignant cases. A good correlation was found between SUVmax1 and SUVmax2. There was significant difference between SUVmax1 and SUVmax2 in the malignant group (p = 0.001). SUVmax1 had superior diagnostic performance than SUVmax2, SUVmax difference and PSA levels, with a sensitivity of 85.4%, a specificity of 100% and an AUC of 0.956. A combination of SUVmax1 with nodal and/or distant metastases and MR PI-RADS V2 score had a sensitivity and specificity of 100%. Delayed pelvic PET/MR imaging in 33 patients were found to be redundant because these patients had nodal and/or distant metastases which can be easily detected by PET/CT. PET/MR provided incremental value in 8 patients at early-stage prostate cancer based on precise anatomical localization and changes in lesion signal provided by MR.Conclusion: Combined 68Ga-PSMA whole-body PET/CT and pelvic PET/MR can accurately differentiate benign prostate diseases from prostate cancer and accurately stage prostate cancer. Whole-body PET/CT is sufficient for advanced prostate cancer. Pelvic PET/MR contributes to diagnosis and accurate staging in early prostate cancer. Imaging at about 1 h after injection is sufficient in most patients.ClinicalTrials.gov: NCT03756077. Registered 27 November 2018—Retrospectively registered, https://clinicaltrials.gov/show/NCT03756077.


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1191
Author(s):  
Steffen Bayerschmidt ◽  
Christian Uprimny ◽  
Alexander Stephan Kroiss ◽  
Josef Fritz ◽  
Bernhard Nilica ◽  
...  

Background: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min post-injection (p.i.) in the detection of LR in patients with biochemical recurrence (BR) of prostate carcinoma. Materials and Methods: 190 image sets of patients with BR in PCa who underwent 68Ga-PSMA-11 PET/CT were assessed retrospectively (median prostate specific antigen (PSA) value, 0.70 ng/mL (range, 0.1–105.6 ng/mL)). Patients received an early static scan of the pelvic area (median, 248 s p.i. (range, 56–923 s)) and a whole-body scan 60 min p.i. (median, 64 min p.i. (range, 45–100 min)) with intravenous administration of 20 mg furosemide i.v. at the time of tracer application, followed by intravenous hydration with 500 mL of sodium chloride (NaCl 0.9%). Assessment was based on visual analysis and calculation of the maximum standardized uptake value (SUVmax) of the pathologic lesions present in the prostate fossa found in the early PET imaging and 60 min PET scans. The scans were characterized as negative, positive, or equivocal. The results were compared, and the combination of early and 60 min p.i. imaging was evaluated. Results: Image assessment resulted in 30 (15.8%) positive, 17 (8.9%) equivocal, and 143 (75.3%) negative findings in early scans, and 28 (14.7%) positive, 25 (13.2%) equivocal, and 137 (72.1%) negative findings of LR in 60 min p.i. images. For combined image analysis, 33 (17.4%) cases were positive and 20 (10.5%) were equivocal. There was no statistical significance between the number of positive (p = 0.815), negative (p = 0.327), and equivocal (p = 0.152) findings. Furthermore, the combination of both scans showed no statistically significant differences for the positive and negative findings (p = 0.063). The median SUVmax was 4.9 (range, 2.0–55.2) for positive lesions in the early scans and 8.0 (range, 2.1–139.9) in the scans 60 min p.i. The median SUVmax for bladder activity was 2.5 (range, 0.9–12.2) in the early scans and 8.2 (range, 1.8–27.6) in the scans 60 min p.i. Conclusion: Early static imaging additional to 68Ga-PSMA-11 PET images acquired 60 min p.i. has limited value in patients prepared with furosemide and hydration, and showed no statistically significant change in the detection rate (DR) of LR and the number of equivocal findings. Based on our results, in departments following a protocol with forced diuresis, including furosemide, additional early static imaging cannot be routinely recommended for the assessment of BR in PCa patients.


2018 ◽  
Vol 64 (6) ◽  
pp. 799-804
Author(s):  
Darya Ryzhkova ◽  
M. Poyda

Purpose: To study the diagnostic value of PET-CT with 68Ga-PSMA-11 in the diagnosis of a primary prostate cancer, preoperative staging, and the detection of recurrence of prostate cancer (PCa). Methods: 28 patients aged 64.7 ± 8.74 years were included. 10 patients primary prostate cancer, and 18 patients with biochemical recurrence of the disease after radical treatment were examined. All patients underwent PET-CT with 68Ga-PSMA-11 according the whole body protocol. Interpretation of images was performed visually and quantitatively by calculation of SUL max. Results: High focal or diffuse 68Ga-PSMA-11 uptake was found in prostate parenchyma in patients with primary prostate cancer. Additionally metastases in regional lymph nodes were diagnosed in 4 patients and bone metastases were found in one patient. The correlation between 68Ga-PSMA-11 uptake level and Gleason index in the primary tumor (R Spearmen = 0.25, p = 0.57) was not observed. PET-positive results were obtained in 14 patients and PET-negative results in 4 patients with biochemical recurrence of PCa. The relationship between the frequency of PET-positive results and Gleason index was not revealed (R Spearmen = 0.2, p = 0.39). We found a weak but significant correlation between the frequency of PET-positive results and the prostate tumor stage according to the T category (R Spearmen = 0.49, p = 0.049). In patients with low values of PSA (less than 1.0 ng/ml) in 4 out of 9 cases, PET-negative results were obtained. In patients with PSA level more than 1.0 ng/ml PET-positive results were obtained in all cases. Conclusions: PET/CT with 68Ga-PSMA-11 allows to diagnose the primary prostate cancer, to establish the stage of the disease in categories N and M, and also to determine the localization and dissemination of the tumor in patients with biochemical recurrence of prostate cancer. The relationship between 68Ga-PSMA-11 uptake in primary tumor and Gleason index was not found. The probability of obtaining PET-positive results in cases of biochemical recurrence is affected by a PSA level above 1 ng/ml and a high stage of the disease according to the T category (T3-T4).


Author(s):  
Simona Malaspina ◽  
Vesa Oikonen ◽  
Anna Kuisma ◽  
Otto Ettala ◽  
Kalle Mattila ◽  
...  

Abstract Purpose This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. Methods Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35–45, 60–88 and 90–118 min. Net influx rates (Ki) were calculated using Patlak plots. Results Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. Conclusion 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. Trial Registration NCT03995888 (24 June 2019).


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pengcheng Hu ◽  
Xin Lin ◽  
Weihai Zhuo ◽  
Hui Tan ◽  
Tianwu Xie ◽  
...  

Abstract Purpose A 2-m axial field-of-view, total-body PET/CT scanner (uEXPLORER) has been recently developed to provide total-body coverage and ultra-high sensitivity, which together, enables opportunities for in vivo time-activity curve (TAC) measurement of all investigated organs simultaneously with high temporal resolution. This study aims at quantifying the cumulated activity and patient dose of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18 FDG ) imaging by using delayed time-activity curves (TACs), measured out to 8-h post-injection, for different organs so that the comparison between quantifying approaches using short-time method (up to 75 min post-injection) or long-time method (up to 8 h post-injection) could be performed. Methods Organ TACs of 10 healthy volunteers were collected using total-body PET/CT in 4 periods after the intravenous injection of F-18 FDG. The 8-h post-injection TACs of 6 source organs were fitted using a spline method (based on Origin (version 8.1)). To compare with cumulated activity estimated from spline-fitted curves, the cumulated activity estimated from multi-exponential curve was also calculated. Exponential curve was fitted with shorter series of data consistent with clinical procedure and previous dosimetry works. An 8-h dynamic bladder wall dose model considering 2 voiding were employed to illustrate the differences in bladder wall dose caused by the different measurement durations. Organ absorbed doses were further estimated using Medical Internal Radiation Dose (MIRD) method and voxel phantoms. Results A short-time measurement could lead to significant bias in estimated cumulated activity for liver compared with long-time-measured spline fitted method, and the differences of cumulated activity were 18.38% on average. For the myocardium, the estimated cumulated activity difference was not statistically significant due to large variation in metabolism among individuals. The average residence time differences of brain, heart, kidney, liver, and lungs were 8.38%, 15.13%, 25.02%, 23.94%, and 16.50% between short-time and long-time methods. Regarding effective dose, the maximum differences of residence time between long-time-measured spline fitted curve and short-time-measured multi-exponential fitted curve was 9.93%. When using spline method, the bladder revealed the most difference in the effective dose among all the investigated organs with a bias up to 21.18%. The bladder wall dose calculated using a long-time dynamic model was 13.79% larger than the two-voiding dynamic model, and at least 50.17% lower than previous studies based on fixed bladder content volume. Conclusions Long-time measurement of multi-organ TACs with high temporal resolution enabled by a total-body PET/CT demonstrated that the clinical procedure with 20 min PET scan at 1 h after injection could be used for retrospective dosimetry analysis in most organs. As the bladder content contributed the most to the effective dose, a long-time dynamic model was recommended for the bladder wall dose estimation.


2008 ◽  
Vol 113 (6) ◽  
pp. 895-904 ◽  
Author(s):  
E. Pelosi ◽  
V. Arena ◽  
A. Skanjeti ◽  
V. Pirro ◽  
A. Douroukas ◽  
...  

2021 ◽  
Author(s):  
Teli Liu ◽  
Chen Liu ◽  
Zhongyi Zhang ◽  
Ning Zhang ◽  
Xiaoyi Guo ◽  
...  

Abstract PurposeDevelop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. Methods64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. Results64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA (+) 22Rv1 cells than PSMA (-) PC-3 cells (5.59±0.36 and 1.97±0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 h to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 4 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. Conclusion64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.


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