Publications by authors named "Karina Knorr"

8 Publications

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PSMA-ligand uptake can serve as a novel biomarker in primary prostate cancer to predict outcome after radical prostatectomy.

EJNMMI Res 2021 Aug 21;11(1):76. Epub 2021 Aug 21.

Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Background: The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immunohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) standardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging biomarker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP).

Methods: In this retrospective analysis, 186 primary prostate cancer patients treated with RP who had undergone a Ga-PSMA-11 PET up to three months prior to the surgery were included. Maximum standardized uptake value (SUV), SUV, tumor volume (TV) and total lesion (TL) were collected from PET-imaging. Moreover, clinicopathological information, including age, serum prostate-specific antigen (PSA) level, and pathological characteristics, was assessed for disease outcome prediction. A stage group system for PET-imaging findings based on the miTNM framework was developed.

Results: At a median follow-up after RP of 38 months (interquartile range (IQR) 22-53), biochemical recurrence (BCR) was observed in 58 patients during the follow-up period. A significant association between a positive surgical margin and miN status (miN1 vs. miN0, odds ratio (OR): 5.428, p = 0.004) was detected. miT status (miT ≥ 3a vs. miT < 3, OR: 2.696, p = 0.003) was identified as an independent predictor for Gleason score (GS) ≥ 8. Multivariate Cox regression analysis indicated that PSA level (hazard ratio (HR): 1.024, p = 0.014), advanced GS (GS ≥ 8 vs. GS < 8, HR: 3.253, p < 0.001) and miT status (miT ≥ 3a vs. miT < 3, HR: 1.941, p = 0.035) were independent predictors for BCR. For stage I disease as determined by PET-imaging, a shorter BCR-free survival was observed in the patients with higher SUV (IA vs. IB stage, log-rank, p = 0.022).

Conclusion: Preoperative miTNM classification from Ga-PSMA-11 PET correlates with postoperative GS, surgical margin status and time to BCR. The association between miTNM staging and outcome proposes Ga-PSMA-11 PET as a novel non-invasive imaging biomarker and potentially serves for ancillary pre-treatment stratification.
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http://dx.doi.org/10.1186/s13550-021-00818-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380207PMC
August 2021

[Positron emission tomography with computed tomography/magnetic resonance imaging for primary staging of prostate cancer].

Radiologe 2021 Sep 5;61(9):818-824. Epub 2021 Aug 5.

Klinik und Poliklinik für Nuklearmedizin, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.

Clinical/methodological Issue: Prostate cancer is the most common malignancy and the second leading cause of cancer-related death in men. Accurate imaging diagnosis and staging are crucial for patient management and treatment. The role of nuclear medicine in the diagnosis of prostate cancer has evolved rapidly in recent years due to the availability of hybrid imaging with radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA).

Standard Radiological Procedures: Hybrid imaging provides higher diagnostic accuracy compared to conventional imaging and has a significant impact on clinical management. Numerous radiotracers have been used in clinical applications, with PSMA ligands being the most commonly used.

Methodological Innovations: Hybrid imaging provides higher diagnostic accuracy for lymph node and bone metastases compared to conventional imaging and has a significant impact on clinical management.

Performance: The high accuracy for primary staging in high-risk prostate cancer using PSMA ligands has led to the inclusion of PSMA positron emission tomography (PET)/computed tomography (CT) in the new German S3 guideline for primary staging of prostate cancer.

Purpose: The aim of this article is to provide an overview of the use of PET imaging in the primary diagnosis of prostate cancer, to present the most commonly used radiotracers, and to highlight the results of recent studies.
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http://dx.doi.org/10.1007/s00117-021-00895-3DOI Listing
September 2021

Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA.

Eur Urol 2021 03 5;79(3):343-350. Epub 2020 Dec 5.

Department of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany; German Cancer Consortium (DKTK), partnersite Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Beta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time.

Objective: To report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.

Design, Setting, And Participants: Twenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects.

Outcome Measurements And Statistical Analysis: Prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured.

Results And Limitations: Sixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval [CI] 1.8-11.2), 4.1 (95% CI 3-14.8), and 7.7 (95% CI 4.5-12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. A limitation is the retrospective design.

Conclusions: Ac-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late-stage mCRPC. Grade 3/4 hematological side effects were observed in up to one-third of patients, and xerostomia led to treatment halt in a relevant number of patients.

Patient Summary: Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.
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http://dx.doi.org/10.1016/j.eururo.2020.11.013DOI Listing
March 2021

First In-Human Medical Imaging with a PASylated Zr-Labeled Anti-HER2 Fab-Fragment in a Patient with Metastatic Breast Cancer.

Nucl Med Mol Imaging 2020 Apr 20;54(2):114-119. Epub 2020 Apr 20.

5Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.

Purpose: PASylation® offers the ability to systematically tune and optimize the pharmacokinetics of protein tracers for molecular imaging. Here we report the first clinical translation of a PASylated Fab fragment (Zr∙Df-HER2-Fab-PAS) for the molecular imaging of tumor-related HER2 expression.

Methods: A patient with HER2-positive metastatic breast cancer received 37 MBq of Zr∙Df-HER2-Fab-PAS at a total mass dose of 70 μg. PET/CT was carried out 6, 24, and 45 h after injection, followed by image analysis of biodistribution, normal organ uptake, and lesion targeting.

Results: Images show a biodistribution typical for protein tracers, characterized by a prominent blood pool 6 h p.i., which decreased over time. Lesions were detectable as early as 24 h p.i. Zr∙Df-HER2-Fab-PAS was tolerated well.

Conclusion: This study demonstrates that a PASylated Fab tracer shows appropriate blood clearance to allow sensitive visualization of small tumor lesions in a clinical setting.
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http://dx.doi.org/10.1007/s13139-020-00638-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198682PMC
April 2020

Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer.

Eur Urol 2019 06 22;75(6):920-926. Epub 2018 Nov 22.

Department of Nuclear Medicine, Medical Center rechts der Isar, Technical University of Munich, Munich, Germany.

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly being used in metastatic castration-resistant prostate cancer (mCRPC). The objective of this study is to report our clinical experience with RLT using 177-lutetium-labeled PSMA-I&T. A total of 100 patients were treated under a compassionate use protocol with a total number of 319 cycles (median two cycles, range 1-6). Eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or chemoineligibility, and positive PSMA-ligand uptake at positron-emission tomography scan. The Lu-PSMA-I&T was given 6-8 weekly with an activity of 7.4 GBq up to six cycles. The median number of previous mCRPC regimens was 3 (range 1-6), and 35 patients had visceral metastases. Prostate-specific antigen decline of ≥50% was achieved in 38 patients, median clinical progression-free survival (cPFS) was 4.1mo, and median overall survival (OS) was 12.9mo. Subgroup analyses identified an association of visceral metastases with a poor prostate-specific antigen (PSA) response and shorter cPFS and OS, and an association of rising lactate dehydrogenase (LDH) with shorter cPFS and OS. Patients achieving PSA decline of ≥50% within 12wk of treatment showed longer cPFS and OS. Treatment-emergent hematologic grade 3/4 toxicities were anemia (9%), thrombocytopenia (4%), and neutropenia (6%). Grade 3/4 nonhematologic toxicities were not observed. RLT with Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage mCRPC at low toxicity. Presence of visceral metastases and rising LDH were associated with worse treatment outcome. PATIENT SUMMARY: We analyzed the treatment outcome and toxicity of prostate-specific membrane antigen-targeted radioligand therapy in patients with metastatic castration-resistant prostate cancer. We found that a good treatment response could be achieved in a subgroup of patients with few side effects. We also observed that treatment outcome was worse in patients with organ metastases and elevated lactate dehydrogenase in blood tests.
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http://dx.doi.org/10.1016/j.eururo.2018.11.016DOI Listing
June 2019

Early Experience of Rechallenge Lu-PSMA Radioligand Therapy After an Initial Good Response in Patients with Advanced Prostate Cancer.

J Nucl Med 2019 05 15;60(5):644-648. Epub 2018 Nov 15.

Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; and.

Our aim was to retrospectively evaluate the feasibility of rechallenge Lu-prostate-specific membrane antigen (Lu-PSMA) radioligand therapy. Rechallenge radioligand therapy was defined as subsequent treatment with Lu-PSMA after initial exposure with an excellent response followed by progression. Biochemical, radiographic, clinical antitumor response, and adverse events were analyzed. Prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival were calculated. Eight patients underwent a median of 2 (range: 1-4) cycles of rechallenge with Lu-PSMA for imaging and therapy. A maximum PSA decrease of 50% was achieved in 3 patients (37.5%). Radiographic response was favorable in 3 patients, whereas 4 exhibited progressive disease. Eastern Cooperative Oncology Group performance status was stable during therapy in all patients. No grade 4 toxicity was noticed, and grade 3 toxicity occurred in 3 patients (37.5%). The median PSA-PFS and overall survival were 3.2 mo (95% confidence interval, 2.6-3.7 mo) and 14.0 mo (95% confidence interval, 6.2-21.8 mo), respectively. In a small patient cohort with an initial excellent response, Lu-PSMA rechallenge is still active, with lower efficacy and higher toxicity.
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http://dx.doi.org/10.2967/jnumed.118.215715DOI Listing
May 2019

Detection Efficacy of F-PSMA-1007 PET/CT in 251 Patients with Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy.

J Nucl Med 2019 03 24;60(3):362-368. Epub 2018 Jul 24.

German Cancer Consortium (DKTK), Heidelberg, Germany.

Prostate-specific membrane antigen (PSMA)-targeted PET imaging recently emerged as a new method for the staging and restaging of prostate cancer. Most published studies investigated the diagnostic potential of Ga-labeled PSMA agents that are excreted renally. F-PSMA-1007 is a novel PSMA ligand that has excellent preclinical characteristics and that is only minimally excreted by the urinary tract, a potential advantage for pelvic imaging. The aim of this study was to investigate the diagnostic efficacy of F-PSMA-1007 for biochemical recurrence (BCR) after radical prostatectomy. From 3 academic centers, 251 patients with BCR after radical prostatectomy were evaluated in a retrospective analysis. Patients who had received second-line androgen deprivation therapy (ADT) or chemotherapy were excluded, but prior first-line ADT exposure was allowed. The median prostate-specific antigen (PSA) level was 1.2 ng/mL (range, 0.2-228 ng/mL). All patients underwent PSMA PET/CT at 92 ± 26 min after injection of 301 ± 46 MBq of F-PSMA-1007. The rate of detection of presumed recurrence sites was correlated with the PSA level and original primary Gleason score. A comparison to a subset of patients treated previously with ADT was undertaken. Of the 251 patients, 204 (81.3%) had evidence of recurrence on F-PSMA-1007 PET/CT. The detection rates were 94.0% (79/84), 90.9% (50/55), 74.5% (35/47), and 61.5% (40/65) for PSA levels of greater than or equal to 2, 1 to less than 2, 0.5 to less than 1, and 0.2 to less than 0.5 ng/mL, respectively. F-PSMA-1007 PET/CT revealed local recurrence in 24.7% of patients ( = 62). Lymph node metastases were present in the pelvis in 40.6% of patients ( = 102), in the retroperitoneum in 19.5% of patients ( = 49), and in supradiaphragmatic locations in 12.0% of patients ( = 30). Bone and visceral metastases were detected in 40.2% of patients ( = 101) and in 3.6% of patients ( = 9), respectively. In tumors with higher Gleason scores (≤7 vs. ≥8), detection efficacy trended higher (76.3% vs. 86.7%) but was not statistically significant ( = 0.32). However, detection efficacy was higher in patients who had received ADT (91.7% vs. 78.0%) within 6 mo before imaging ( = 0.0179). F-PSMA-1007 PET/CT offers high detection rates for BCR after radical prostatectomy that are comparable to or better than those published for Ga-labeled PSMA ligands.
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http://dx.doi.org/10.2967/jnumed.118.212233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424235PMC
March 2019

Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging.

J Nucl Med 2018 09 25;59(9):1406-1411. Epub 2018 Jan 25.

Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

The study aims to investigate the presence of physiologic prostate-specific membrane antigen (Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. Four hundred seven patients who underwent Glu-NH-CO-NH-Lys radiolabeled with Ga-gallium -bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine--diacetic acid (Ga-PSMA-HBED-CC) PET (combined with a diagnostic CT) were retrospectively analyzed. The number of Ga-PSMA PET-positive cervical, celiac, and sacral ganglia was determined, and the configuration and SUV of each ganglion were measured. In addition, the configuration and SUV of adjacent lymph node metastases in the respective region (cervical, celiac, or sacral) were determined. Ga-PSMA-ligand uptake above background was detected in 401 (98.5%) patients in any peripheral ganglia, in 369 (92%) patients in cervical ganglia, in 363 (89%) patients in celiac ganglia, and in 183 (46%) patients in sacral ganglia. The Ga-PSMA-ligand uptake was highest in celiac (mean SUV, 2.9 ± 0.8 vs. cervical mean SUV, 2.4 ± 0.6) and sacral (mean SUV 1.7 ± 0.5; both < 0.0001) ganglia. Intraindividually there was a statistically significant but weak to moderate correlation between the Ga-PSMA-ligand uptake in cervical versus celiac ganglia ( = 0.34, < 0.0001), cervical versus sacral ( = 0.52, < 0.0001), and celiac versus sacral ( = 0.16, < 0.05). The Ga-PSMA-ligand uptake was significantly more intense in adjacent lymph node metastases than the respective ganglia (cervical: 18.0 ± 16.2 vs. 2.4 ± 0.6, < 0.0001; celiac: 13.5 ± 12.3 vs. 2.9 ± 0.8, < 0.0001; sacral: 13.4 ± 11.6 vs. 1.7 ± 0.5, < 0.0001). Furthermore, ganglia predominantly exhibit a band-shaped configuration (71.2%), followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%). Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more often show teardrop (40.3%) or nodular appearance (58.6%) ( < 0.00001). Ga-PSMA-ligand uptake in ganglia along the sympathetic trunk as assessed by Ga-PSMA-HBED-CC PET represents an important pitfall in prostate cancer PET imaging. The Ga-PSMA-ligand uptake is higher in celiac ganglia than cervical or sacral ganglia, and the level of Ga-PSMA-ligand uptake seems to be patient-related. For the differentiation between lymph node metastases and sympathetic ganglia, both intensity of Ga-PSMA-ligand uptake and exact localization and configuration of the respective lesion should be examined carefully.
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http://dx.doi.org/10.2967/jnumed.117.204677DOI Listing
September 2018
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