Dataset Information

Performance of [⁶⁸Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy-a multi-centre evaluation of 2533 patients.

ABSTRACT:

Purpose

To evaluate the performance of [⁶⁸Ga]Ga-PSMA-11 PET/CT in the diagnosis of recurrent prostate cancer (PC) after prostatectomy in a large multicentre cohort.

Methods

The centres, which contributed to this study, were the departments of nuclear medicine of Heidelberg (Germany), Technical University of Munich (Germany) and Albert Einstein Hospital of São Paulo (Brazil). A total of 2533 patients who were scanned with [⁶⁸Ga]Ga-PSMA-11 PET/CT at 1 h p.i. due to recurrent PC after prostatectomy were included in this retrospective analysis. Exclusion criteria were as follows: patients with untreated primary tumour, previous chemotherapy or Xofigo®; those previously treated with exclusively external beam radiation therapy or HIFU; those referred for PSMA-therapy; and those treated with ADT (including first- and second-generation ADT) within the last 6 months. Potential influences of different factors such as PSA level, PSA doubling-time (PSA_DT), PSA velocity (PSA_Vel), Gleason Score (GSC, including the separate analysis of 7a and 7b), age and amount of injected tracer were evaluated in a multivariable analysis.

Results

The rate of pathologic PET/CT-scans was 43% for PSA ≤ 0.2 ng/ml, 58% for PSA > 0.2 to ≤ 0.5, 72% for PSA > 0.5 to ≤ 1.0 and increased to a maximum of 93% for PSA > 10 ng/ml. A pathological PET/CT was significantly (p = 0.001) associated with PSA level and higher GSC. Amount of injected tracer, age, PSA_DT and PSA_Vel were not associated with a higher probability of a pathological scan.

Conclusion

[⁶⁸Ga]Ga-PSMA-11 PET/CT at 1 h p.i. confirmed its high performance in the largest patient cohort yet analysed. Tumour detection showed a clear association with higher PSA and higher GSC. No association was found between a pathological [⁶⁸Ga]Ga-PSMA-11 PET/CT and age, amount of injected tracer, PSA_DT or PSA_Vel.

SUBMITTER: Afshar-Oromieh A

PROVIDER: S-EPMC8263399 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:18F-labeled prostate-specific membrane antigen (PSMA)-ligand PET has several principal advantages over 68Ga-PSMA-11. The purpose of this retrospective study was to evaluate the frequency of non-tumor-related uptake and the detection efficacy comparing 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT in recurrent prostate cancer (PC) patients. Methods: The study included 102 patients with biochemically recurrent PC after radical prostatectomy undergoing 18F-PSMA-1007 PET/CT imaging. On the basis of various clinical variables, patients with corresponding 68Ga-PSMA-11 PET/CT scans were matched. All PET/CT scans (n = 204) were reviewed by 1 nuclear medicine physician. First, all PET-positive lesions were noted. Then, lesions suspected of being recurrent PC were differentiated from lesions attributed to a benign origin on the basis of known pitfalls and information from CT. For each region, the SUVmax of the lesion with the highest PSMA-ligand uptake was noted. Detection rates were determined, and SUVmax was compared separately for 68Ga-PSMA-11 and 18F-PSMA-1007. Results: In total, 18F-PSMA-1007 PET and 68Ga-PSMA-11 PET revealed 369 and 178 PSMA-ligand-positive lesions, respectively. 18F-PSMA-1007 PET revealed approximately 5 times more lesions attributed to a benign origin than did 68Ga-PSMA-11 PET (245 vs. 52 lesions, respectively). The benign lesions most frequently observed were ganglia, unspecific lymph node, and bone lesions, at a rate of 43%, 31%, and 24% for 18F-PSMA-1007 PET and 29%, 42%, and 27% for 68Ga-PSMA-11 PET, respectively. The SUVmax of lesions attributed to a benign origin was significantly higher (P < 0.0001) for 18F-PSMA-1007 PET. Further, a similar number of lesions was attributed to recurrent PC (124/369 for 18F-PSMA-1007 PET and 126/178 for 68Ga-PSMA-11 PET). Conclusion: The number of lesions with increased PSMA-ligand uptake attributed to a benign origin is considerably higher for 18F-PSMA-1007 PET than for 68Ga-PSMA-11 PET. This finding indicates the need for sophisticated reader training emphasizing known pitfalls and reporting within the clinical context.

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:Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with 68Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and 68Ga-RM2 (68Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm3), 68Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and 68Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered 68Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of 68Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for 68Ga-RM2. Median 68Ga-RM2 SUVmax was significantly higher than median 68Ga-PSMA-617 SUVmax in the ISUP-2 subgroup (P = 0.01). Conclusion: 68Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and 68Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.

Project description:PurposeIn PSMA-ligand PET/CT imaging, standardized evaluation frameworks and image-derived parameters are increasingly used to support prostate cancer staging. Clinical applicability remains challenging wherever manual measurements of numerous suspected lesions are required. Deep learning methods are promising for automated image analysis, typically requiring extensive expert-annotated image datasets to reach sufficient accuracy. We developed a deep learning method to support image-based staging, investigating the use of training information from two radiotracers.MethodsIn 173 subjects imaged with 68Ga-PSMA-11 PET/CT, divided into development (121) and test (52) sets, we trained and evaluated a convolutional neural network to both classify sites of elevated tracer uptake as nonsuspicious or suspicious for cancer and assign them an anatomical location. We evaluated training strategies to leverage information from a larger dataset of 18F-FDG PET/CT images and expert annotations, including transfer learning and combined training encoding the tracer type as input to the network. We assessed the agreement between the N and M stage assigned based on the network annotations and expert annotations, according to the PROMISE miTNM framework.ResultsIn the development set, including 18F-FDG training data improved classification performance in four-fold cross validation. In the test set, compared to expert assessment, training with 18F-FDG data and the development set yielded 80.4% average precision [confidence interval (CI): 71.1-87.8] for identification of suspicious uptake sites, 77% (CI: 70.0-83.4) accuracy for anatomical location classification of suspicious findings, 81% agreement for identification of regional lymph node involvement, and 77% agreement for identification of metastatic stage.ConclusionThe evaluated algorithm showed good agreement with expert assessment for identification and anatomical location classification of suspicious uptake sites in whole-body 68Ga-PSMA-11 PET/CT. With restricted PSMA-ligand data available, the use of training examples from a different radiotracer improved performance. The investigated methods are promising for enabling efficient assessment of cancer stage and tumor burden.

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.

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:Background/aimProstate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment.Materials and methodsThis analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy.ResultsOne-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001).ConclusionLow PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Dataset Information

Performance of [⁶⁸Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy-a multi-centre evaluation of 2533 patients.

Purpose

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Performance of [68Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy-a multi-centre evaluation of 2533 patients.

Purpose

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Performance of [⁶⁸Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy-a multi-centre evaluation of 2533 patients.