Dataset Information

Intra-individual dynamic comparison of ¹⁸F-PSMA-11 and ⁶⁸Ga-PSMA-11 in LNCaP xenograft bearing mice.

ABSTRACT: Recently, a ¹⁸F-labeled derivative of the widely used ⁶⁸Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although ¹⁸F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with ¹⁸F-PSMA-11 or ⁶⁸Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received?±?3.7 MBq ¹⁸F-PSMA-11 and ⁶⁸Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as?±?15 MBq ¹⁸F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUV_mean, SUV_max, TBR_mean and TBR_max). Mice underwent ex vivo biodistribution where ¹⁸F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (K_d) of ¹⁸F-PSMA-11 and ⁶⁸Ga-PSMA-11 was 2.95?±?0.87 nM and 0.49?±?0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both ¹⁸F-PSMA-11 and ⁶⁸Ga-PSMA-11, while no difference was found for ¹⁸F-FDG uptake (except for SUV_max). Tumor uptake of ¹⁸F-PSMA-11 showed a similar trend over time as ⁶⁸Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBR_mean and TBR_max were significantly higher at the later timepoint, as well as the SUV_max of ⁶⁸Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0?±?13.6%ID/g 1 h p.i.) and the bladder (6.48?±?2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for ¹⁸F-PSMA-11 compared to ⁶⁸Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late ¹⁸F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of ¹⁸F-PSMA-11 as well as no significant increase in bone uptake.

SUBMITTER: Piron S

PROVIDER: S-EPMC7713063 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice.

Piron Sarah S Verhoeven Jeroen J Descamps Benedicte B Kersemans Ken K De Man Kathia K Van Laeken Nick N Pieters Leen L Vral Anne A Vanhove Christian C De Vos Filip F

Scientific reports 20201203 1

Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by deter ...[more]

PMID: 33273603

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Project description:PurposeDetailed data comparing the biodistribution of PSMA radioligands is still scarce, raising concerns regarding the comparability of different compounds. We investigated differences in normal-organ biodistribution and uptake variability between the two most commonly PSMA tracers in clinical use, 68Ga-PSMA-11 and 18F-DCFPyL.MethodsThis retrospective analysis included 34 patients with low tumor burden referred for PET/CT imaging with 68Ga-PSMA-11 and subsequently 18F-DCFPyL. Images were acquired with 4 cross-calibrated PET/CT systems. Volumes of interest were placed on major salivary and lacrimal glands, liver, spleen, duodenum, kidneys, bladder, blood-pool and muscle. Normal-organ biodistribution of both tracers was then quantified as SUVpeak and compared using paired tests, linear regression and Bland-Altman analysis. Between-patient variability was also assessed. Clinical and protocol variables were investigated for possible interference.ResultsFor both tracers the highest uptake was found in the kidneys and bladder and low background activity was noted across all scans. In the quantitative analysis there was significantly higher uptake of 68Ga-PSMA-11 in the kidneys, spleen and major salivary glands (p < 0.001), while the liver exhibited slightly higher 18F-DCFPyL uptake (p = 0.001, mean bias 0.79 ± 1.30). The lowest solid-organ uptake variability was found in the liver (COV 21.9% for 68Ga-PSMA-11, 22.5% for 18F-DCFPyL). There was a weak correlation between 18F-DCFPyL uptake time and liver SUVpeak (r = 0.488, p = 0.003) and, accordingly, patients scanned at later time-points had a larger mean bias between the two tracers' liver uptake values (0.05 vs 1.46, p = 0.001).ConclusionNormal tissue biodistribution patterns of 68Ga-PSMA-11 and 18F-DCFPyL were similar, despite subtle differences in quantitative values. Liver uptake showed an acceptable intra-patient agreement and low inter-patient variability between the two tracers, allowing its use as a reference organ for thresholding scans in the qualitative comparison of PSMA expression using these different tracers.

Project description:Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced 68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

Project description:BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

Project description:PurposeWe aimed to compare the diagnostic performance and biodistribution of two similar PET agents, [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11, in the same group of primary prostate cancer (PCa) patients.MethodsFifty patients with untreated, histologically confirmed PCa by needle biopsy were enrolled. Each patient underwent [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT within a week. In addition to visual analysis, the standardized uptake value (SUV) was measured for semiquantitative comparison and correlation analysis.Results[68Ga]Ga-P16-093 PET/CT detected more positive tumors than [68Ga]Ga-PSMA-11 PET/CT (202 vs. 190, P = 0.002), both for intraprostatic lesions (48 vs. 41, P = 0.016) and metastatic lesions (154 vs. 149, P = 0.125), especially for intraprostatic lesions in low- and intermediate-risk PCa patients (21/23 vs. 15/23, P = 0.031). Furthermore, [68Ga]Ga-P16-093 PET/CT exhibited a significantly higher SUVmax for most matched tumors (13.7 ± 10.2 vs. 11.4 ± 8.3, P < 0.001). For normal organs, [68Ga]Ga-P16-093 PET/CT showed significantly lower activity in the kidney (SUVmean: 20.1 ± 6.1 vs. 29.3 ± 9.1, P < 0.001) and urinary bladder (SUVmean: 6.5 ± 7.1 vs. 20.9 ± 17.4, P < 0.001), but displayed a higher uptake in the parotid gland (SUVmean: 8.7 ± 2.6 vs. 7.6 ± 2.1, P < 0.001), liver (SUVmean: 7.0 ± 1.9 vs. 3.7 ± 1.3, P < 0.001), and spleen (SUVmean: 8.2 ± 3.0 vs. 5.2 ± 2.2, P < 0.001) than [68Ga]Ga-PSMA-11 PET/CT.Conclusion[68Ga]Ga-P16-093 PET/CT demonstrated higher tumor uptake and better tumor detectability than [68Ga]Ga-PSMA-11 PET/CT, especially in low- and intermediate-risk PCa patients, which indicated that [68Ga]Ga-P16-093 may serve as an alternative agent for detection of PCa.Trial registration68Ga-P16-093 and 68Ga-PSMA-11 PET/CT Imaging in the Same Group of Primary Prostate Cancer Patients (NCT05324332, Registered 12 April 2022, retrospectively registered). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT05324332 .

Project description:Background68Ga-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.MethodsSix 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).ConclusionThe effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

Project description:PurposeThis study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [68Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence.ProceduresUnder IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [68Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [68Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~ 60 min and ~ 140 min post-[68Ga]Ga-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using IDAC Dose 2.1. The prior [68Ga]Ga-PSMA-11 PET/CT exam (whole-body PET imaging at 60 min post-injection, performed with contrast-enhanced diagnostic CT) served as a reference scan for comparison to the [68Ga]Ga-P16-093 findings.Results[68Ga]Ga-P16-093 PET images at 60 min post-injection provided diagnostic information that appeared equivalent to the subject's prior [68Ga]Ga-PSMA-11 scan. With both radiopharmaceuticals, sites of tumor recurrence were found in eight of the ten patients, identifying 16 lesions. The site of recurrence was not detected with either agent for the other two subjects. Bladder activity was consistently lower with [68Ga]Ga-P16-093 than [68Ga]Ga-PSMA-11. The kidneys, spleen, salivary glands, and liver receive the highest radiation exposure from [68Ga]Ga-P16-093, with estimated doses of 1.7 × 10-1, 6.7 × 10-2, 6.5 × 10-2, and 5.6 × 10-2 mGy/MBq, respectively. The corresponding effective dose from [68Ga]Ga-P16-093 is 2.3 × 10-2 mSv/MBq.Conclusions[68Ga]Ga-P16-093 provided diagnostic information that appeared equivalent to [68Ga]Ga-PSMA-11 in this limited series of ten prostate cancer patients presenting with biochemical recurrence, with the kidneys found to be the critical organ. Diminished tracer appearance in the urine represents a potential advantage of [68Ga]Ga-P16-093 over [68Ga]Ga-PSMA-11 for detection of lesions in the pelvis.

Dataset Information

Intra-individual dynamic comparison of ¹⁸F-PSMA-11 and ⁶⁸Ga-PSMA-11 in LNCaP xenograft bearing mice.

Publications

Intra-individual dynamic comparison of <sup>18</sup>F-PSMA-11 and <sup>68</sup>Ga-PSMA-11 in LNCaP xenograft bearing mice.

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