Monosodium glutamate reduces 68Ga-PSMA-11 uptake in salivary glands and kidneys in preclinical prostate cancer model.
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ABSTRACT:
SUBMITTER: Rousseau E
PROVIDER: S-EPMC6278899 | biostudies-other | 2018 Aug
REPOSITORIES: biostudies-other
Publications
Monosodium Glutamate Reduces <sup>68</sup>Ga-PSMA-11 Uptake in Salivary Glands and Kidneys in a Preclinical Prostate Cancer Model.
Rousseau Etienne E Lau Joseph J Kuo Hsiou-Ting HT Zhang Zhengxing Z Merkens Helen H Hundal-Jabal Navjit N Colpo Nadine N Lin Kuo-Shyan KS Bénard François F
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20180810 12
We evaluated the ability of monosodium glutamate (MSG) to reduce salivary and kidney uptake of a prostate-specific membrane antigen (PSMA) radioligand without affecting tumor uptake. <b>Methods:</b> LNCaP tumor-bearing mice were intraperitoneally injected with MSG (657, 329, or 164 mg/kg) or phosphate-buffered saline (PBS). Fifteen minutes later, the mice were intravenously administered <sup>68</sup>Ga-PSMA-11. PET/CT imaging and biodistribution studies were performed 1 h after administration. < ...[more]
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Project description:Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting the prostate-specific membrane antigen (PSMA) with a 68Ga-labelled PSMA-analog (68Ga-PSMA-11) is discussed as a promising diagnostic method for patients with suspicion or history of prostate cancer. One potential drawback of this method are severe photopenic (halo-) artifacts surrounding the bladder and the kidneys in the scatter-corrected PET images, which have been reported to occur frequently in clinical practice. The goal of this work was to investigate the occurrence and impact of these artifacts and, secondly, to evaluate variants of the standard scatter correction method with regard to halo-artifact suppression.Experiments using a dedicated pelvis phantom were conducted to investigate whether the halo-artifact is modality-, tracer-, and/or concentration-dependent. Furthermore, 31 patients with history of prostate cancer were selected from an ongoing 68Ga-PSMA-11-PET/MRI study. For each patient, PET raw data were reconstructed employing six different variants of PET scatter correction: absolute scatter scaling, relative scatter scaling, and relative scatter scaling combined with prompt gamma correction, each of which was combined with a maximum scatter fraction (MaxSF) of MaxSF = 75% or MaxSF = 40%. Evaluation of the reconstructed images with regard to halo-artifact suppression was performed both quantitatively using statistical analysis and qualitatively by two independent readers.The phantom experiments did not reveal any modality-dependency (PET/MRI vs. PET/CT) or tracer-dependency (68Ga vs. 18F-FDG). Patient- and phantom-based data indicated that halo-artifacts derive from high organ-to-background activity ratios (OBR) between bladder/kidneys and surrounding soft tissue, with a positive correlation between OBR and halo size. Comparing different variants of scatter correction, reducing the maximum scatter fraction from the default value MaxSF = 75% to MaxSF = 40% was found to efficiently suppress halo-artifacts in both phantom and patient data. In 1 of 31 patients, reducing the maximum scatter fraction provided new PET-based information changing the patient's diagnosis.Halo-artifacts are particularly observed for 68Ga-PSMA-11-PET/MRI due to 1) the biodistribution of the PSMA-11-tracer resulting in large OBRs for bladder and kidneys and 2) inaccurate scatter correction methods currently used in clinical routine, which tend to overestimate the scatter contribution. If not compensated for, 68Ga-PSMA-11 uptake pathologies may be masked by halo-artifacts leading to false-negative diagnoses. Reducing the maximum scatter fraction was found to efficiently suppress halo-artifacts.
| S-EPMC5560715 | biostudies-other
Project description:Purpose:To preliminarily evaluate the feasibility and potential of using 68Ga-PSMA-11 PET/CT in evaluating the function of salivary glands and lacrimal glands in comparison with 99mTc-pertechnetate (99mTcO4 -) salivary gland scintigraphy (SGS). Methods:A retrospective study was performed in 15 patients with different degrees of xerostomia and suspected salivary gland dysfunction. Each patient underwent 68Ga-PSMA-11 PET/CT first and SGS the next day, and the findings of both scans were compared. Results:The results of 68Ga-PSMA-11 PET/CT and SGS were consistent in 12/15 patients (80%) and were inconsistent in the remaining patients (20%). For 5 (33.3%) of 15 patients, 68Ga-PSMA-11 PET/CT provided more information than did SGS. Additionally, 68Ga-PSMA-11 PET/CT corrected the misdiagnosis by SGS for 1 patient. Conclusions:68Ga-PSMA-11 PET/CT is a potentially useful imaging tool for evaluating the function of salivary glands and lacrimal glands. 68Ga-PSMA-11 PET/CT can be a promising supplement to SGS, and its clinical value deserves further study.
| S-EPMC7201830 | biostudies-literature
Project description:BACKGROUND:68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients. METHODS:Six low-risk prostate cancer patients were injected with 133-178?MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255?min post-injection. Urine was collected up to 4?h post-injection, and venous blood samples were drawn at 45?min, 85?min, 175?min, and 245?min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods. RESULTS:[68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5?min (91%) and 4.4?h (9%). The effective dose was calculated to 0.022?mSv/MBq. The kidneys received approximately 40?mGy after an injection with 160?MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12?mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051?mGy/MBq). CONCLUSION:The effective dose for [68Ga]PSMA-11 is 0.022?mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.
| S-EPMC6328430 | biostudies-literature
Project description:We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.
| S-EPMC5355341 | biostudies-literature
Project description:BACKGROUND:Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50-60% of patients. SRT is commonly initiated in patients with serum PSA levels <?1?ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT. METHODS:We will randomize 193 patients to proceed with standard SRT (control arm 1, n?=?90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n?=?103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA???0.2?ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5?years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death. DISCUSSION:This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy. ACRONYM:PSMA-SRT Phase 3 trial. CLINICAL TRIAL REGISTRATION:? IND#130649 ? Submission: 04.26.2016 ? Safe-to-proceed letter issued by FDA: 05.25.2016 ? UCLA IRB #18-000484, ? First submission: 3.27.2018 ? Date of approval: 5.31.2018 ? UCLA JCCC Short Title NUC MED 18-000484 ? NCI Trial Identifier NCI-2018-01518 ? ClinicalTrials.gov Identifier NCT03582774 ? First Submitted: 06.19.2018 ? First Submitted that Met QC Criteria: 06.27.2018 ? First Posted: 07.11.2018 ? Last Update Submitted that Met QC Criteria: 07.17.2018 ? Last Update Posted: 07.19.2018 TRIAL STATUS: Current Trial Status Active as of 08/13/2018 Trial Start Date 09/01/2018-Actual Primary Completion Date 09/01/2023-Anticipated Trial Completion Date 09/01/2024-Anticipated.
| S-EPMC6322287 | biostudies-literature
Project description:Objective:To synthesize 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) with a synthesis module and investigate PET-CT imaging to monitor PSMA expression during prostate cancer (PCa) progression and tumor growth in mice bearing subcutaneous PCa xenografts. Method:The radiochemical purity and stability of??68Ga-PSMA-11 were determined via radio-HPLC. The PCa cell lines of different PSMA expression levels (PC3, VCAP±, CWR22RV1+, and LNCaP++) were selected to mimic the PCa progression. 68Ga-PSMA-11 biodistribution was studied by dissection method and in vivo imaging with micro PET-CT. The expression levels of PSMA in tumor cells and tissues were analyzed by immunofluorescence, flow cytometry, and western blot. The correlation between PSMA expression and radio-uptake was also evaluated. 2-PMPA preadministration served as a block group. Results:The radiochemical purity of??68Ga-PSMA-11 was 99.6 ± 0.1% and stable in vitro for 2?h. The equilibrium binding constant (Kd) of??68Ga-PSMA-11 to LNCaP, CWR22Rv1, PC-3, and VCAP cells was 4.3 ± 0.8?nM, 16.4 ± 1.3?nM, 225.3 ± 20.8?nM, and 125.6 ± 13.1?nM, respectively. Results of tumor uptake (% ID and % ID/g or % ID/cm3) of??68Ga-PSMA-11 in biodistribution and micro PET imaging were LNCaP > CWR22RV1 > PC-3 and VCAP due to different PSMA expression levels. It was confirmed by flow cytometry, western blot, and immunofluorescence. Tumor uptake (% ID/cm3) of??68Ga-PSMA-11 increased with the tumor anatomical volume in quadratic polynomial fashion and reached the peak (when tumor volume was 0.5?cm3) earlier than tumor uptake (% ID). Tumor uptake (% ID/cm3) of??68Ga-PSMA-11 based on functional volume correlated well with the PSMA expression in a linear manner (y = 9.35x + 2.59, R2 = 0.8924, and p < 0.0001); however, low dose 2-PMPA causes rapid renal clearance of increased tumor/kidney uptake of??68Ga-PSMA-11. Conclusions:The 68Ga-PSMA-11 PET-CT imaging could invasively evaluate PSMA expression during PCa progression and tumor growth with % ID/cm3 (based on functional volume) as an important index. Low dose 2-PMPA preadministration might be a choice to decrease kidney uptake of??68Ga-PSMA-11.
| S-EPMC5944242 | biostudies-literature
Project description:RationalePSMA-directed therapy for metastatic prostate cancer is gaining adoption as a treatment option. However, accumulation of 177Lu/225Ac-PSMA in the salivary glands remains a problem, with risk of dose-limiting xerostomia and potentially severe effect on the quality of life. Gustatory stimulation is an approach that has commonly been used in radioactive iodine therapy to reduce accumulation in the salivary glands. However, based on theoretical differences in biodistribution, it was hypothesized that this could potentially lead to adverse increased toxicity for PSMA-ligand therapy. The primary objective of this work was to determine if gustatory stimulation by eating an assortment of sweet/fatty/acidic foods during the biodistribution phase of [18F]DCFPyl could result in a clinically relevant (> 30%) change in the uptake of the tracer in the salivary glands.Methods10 patients who already received a whole-body [18F]DCFPyl PET/CT scan for evaluation of prostate cancer, underwent a repeat (intervention) PET/CT scan within a month of the first (control) scan. During the intervention scan, patients chose from an assortment of sweet/fatty/acidic foods, which they then chewed and swallowed for a period of time starting 1 min before tracer administration to 10 min thereafter. Data from both scans were analyzed by placing VOIs on the major salivary glands and segmenting them using relative thresholds.ResultsA slight increase in PSMA uptake in the parotid glands was observed on the intervention scan when compared to the baseline scan (+ 7.1% SULmean and + 9.2% SULmax, p < 0.05). No significant difference in PSMA uptake in the submandibular glands was seen.ConclusionsEating only slightly increases uptake of [18F]DCFPyl in the parotid glands. We nonetheless recommend refraining from gustatory stimulation during the administration and early biodistribution phase of radionuclide therapy with PSMA-ligands to reduce the risk of avoidable additional toxicity.
| S-EPMC8473516 | biostudies-literature
Project description:BACKGROUND:In this study, we investigate the impact of increased PET acquisition time per bed position on lesion detectability, standard uptake value, and image noise in 68Ga-PSMA-11 PET/MRI scans. METHODS:Scans of twenty patients were analyzed in this study. Patients were injected with 68Ga-PSMA-11 (mean, 5.50?±?1.49?mCi) and imaged on a 3.0 T time-of-flight PET/MRI. PET images were retrospectively reconstructed using 0.5, 1, 2, 4, 7, and 10?min of PET data. Lesion detectability was evaluated on a 5-point Likert Scale for each lesion in each reconstruction. Quantitative analysis was performed measuring image noise and lesion uptake. RESULTS:A total of 55 lesions were identified, and lesion detectability increased from 2.07?±?1.14 for 0.5?min to 4.93?±?0.26 for 10?min (p?<?0.001), with no significant difference detected between 7 and 10?min of scan time. Average SUVmax decreased from 9.89?±?6.62 for 0.5?min to 8.64?±?6.81 for 10 min. Noise decreased from 0.72?±?0.22 for 0.5?min to 0.31?±?0.12 for 10?min (p?<?0.001) and were nearly equivalent between 7 and 10?min. Pairwise interaction terms between size, SUVmax, and scan time were all found to be significant, although the interaction term between SUVmax and scan time was found to be the most significant. CONCLUSIONS:Increased acquisition duration improves image quality by increasing detectability and reducing noise. In patients with biochemical recurrence, increased acquisition time up to 7?min improves lesion detection.
| S-EPMC7447708 | biostudies-literature
Project description:Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa. Our objective was to investigate whether PSMA-expression patterns of the primary tumour on immunohistochemistry (IHC) are associated with PSMA-PET detection rate of recurrent PCa. Methods: Retrospective institutional review board approved single-centre analysis of patients who had undergone 68Ga-PSMA-11-PET for BCR after radical prostatectomy (RPE) between 04/2016 and 07/2019, with tumour specimens available for PSMA-IHC. Clinical information (age, PSA-level, ongoing androgen deprivation therapy (ADT), Gleason score) and PSMA-IHC of the primary tumour were collected and their relationship to results from PSMA-PET (positive/negative) was investigated using a multiple logistic regression analysis. Results: 120 PSMA-PET scans in 74 patients were available for this analysis. Overall detection rate was 62% (74/120 scans), with a mean PSA value at scan time of 0.99 ng/ml (IQR 0.32-4.27). Of the clinical factors, only PSA-level and ADT were associated with PSMA-PET positivity. The percentage of PSMA-negative tumour area on IHC (PSMA%neg) had a significant association to PSMA-PET negativity (OR = 2.88, p < 0.001), while membranous PSMA-expression showed no association (p = 0.73). The positive predictive value of PSMA%neg ? 50% for a negative PSMA-PET was 85% (13/11) and for a PSMA%neg of 80% or more, 100% (9/9). Conclusions: PSMA-negative tumour area on IHC exhibited the strongest association with negative PSMA-PET scans, beside PSA-level and ADT. Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA%neg ? 50%.
| S-EPMC7255040 | biostudies-literature
Project description:IntroductionDynamic PET/CT allows visualization of pharmacokinetics over the time, in contrast to static whole body PET/CT. The objective of this study was to assess 68Ga-PSMA-11 uptake in pathological lesions and benign tissue, within 30 minutes after injection in primary prostate cancer (PCa) patients in test-retest setting.Materials and methodsFive patients, with biopsy proven PCa, were scanned dynamically in list mode for 30 minutes on a digital PET/CT-scanner directly after an intravenous bolus injection of 100 MBq 68Ga-PSMA-11. Approximately 45 minutes after injection a static whole body scan was acquired, followed by a one bed position scan of the pelvic region. The scans were repeated approximately four weeks later, without any intervention in between. Semi-quantitative assessment was performed using regions-of-interest in the prostate tumor, bladder, gluteal muscle and iliac artery. Time-activity curves were extracted from the counts in these regions and the intra-patient variability between both scans was assessed.ResultsThe uptake of the iliac artery and gluteal muscle reached a plateau after 5 and 3 minutes, respectively. The population fell apart in two groups with respect to tumor uptake: in some patients the tumor uptake reached a plateau after 5 minutes, whereas in other patients the uptake kept increasing, which correlated with larger tumor volumes on PET/CT scan. Median intra-patient variation between both scans was 12.2% for artery, 9.7% for tumor, 32.7% for the bladder and 14.1% for the gluteal muscle.ConclusionDynamic 68Ga-PSMA-11 PET/CT scans, with a time interval of four weeks, are reproducible with a 10% variation in uptake in the primary prostate tumor. An uptake plateau was reached for the iliac artery and gluteal muscle within 5 minutes post-injection. A larger tumor volume seems to be related to continued tumor uptake. This information might be relevant for both response monitoring and PSMA-based radionuclide therapies.
| S-EPMC7853454 | biostudies-literature