25 results on '"Kürpig S"'
Search Results
2. Theranostics in nuclear medicine practice
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Yordanova A, Eppard E, Kürpig S, Bundschuh RA, Schönberger S, Gonzalez-Carmona M, Feldmann G, Ahmadzadehfar H, and Essler M
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theranostics ,nuclear medicine ,personalized medicine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Anna Yordanova,1 Elisabeth Eppard,2 Stefan Kürpig,2 Ralph A Bundschuh,3 Stefan Schönberger,4 Maria Gonzalez-Carmona,5 Georg Feldmann,6 Hojjat Ahmadzadehfar,1 Markus Essler1 1Department of Nuclear Medicine (Clinical Nuclear Medicine), 2Department of Nuclear Medicine (Radiochemistry), 3Department of Nuclear Medicine (Medical Physics and PET), 4Department of Paediatric Haematology and Oncology, 5Department of Medicine 1, 6Department of Medicine 3, University Hospital Bonn, Bonn, Germany Abstract: The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices. Keywords: theranostics, nuclear medicine, personalized medicine, PET/CT, therapy, diagnostics
- Published
- 2017
3. Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga–PSMA uptake in LNCaP cells
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Mathy, C. S., Mayr, T., Kürpig, S., Meisenheimer, M., Dolscheid-Pommerich, R. C., Stoffel-Wagner, B., Kristiansen, G., Essler, M., Muders, M. H., and Bundschuh, R. A.
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- 2021
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4. Therapeutic response and side effects of repeated radioligand therapy with 177Lu- PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer
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Ahmadzadehfar, H., Eppard, E., Kürpig, S., Fimmers, R., Yordanova, A., Schlenkhoff, C.D., Rogenhofer, S., and Essler, M.
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ddc: 610 ,610 Medical sciences ,Medicine ,urologic and male genital diseases - Abstract
Introduction: Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer, making it an optimal target for the treatment of metastasized prostate cancers. Radioligand therapy (RLT) with 177Lu- PSMA-DKFZ-617 (Lu-PSMA) is a novel[for full text, please go to the a.m. URL], 62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie
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- 2016
5. Therapeutic response and side effects of repeated radioligand therapy with 177Lu- PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer
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Ahmadzadehfar, H, Eppard, E, Kürpig, S, Fimmers, R, Yordanova, A, Schlenkhoff, CD, Rogenhofer, S, Essler, M, Ahmadzadehfar, H, Eppard, E, Kürpig, S, Fimmers, R, Yordanova, A, Schlenkhoff, CD, Rogenhofer, S, and Essler, M
- Published
- 2016
6. Diagnosis of periprosthetic loosening of total hip and knee arthroplasty using 68Gallium-Zoledronate PET/CT.
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Touet, A., Koob, S., Kürpig, S., Roos, J., Roesch, F., Wirtz, DC., Essler, M., and Gaertner, FC.
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TOTAL knee replacement , *TOTAL hip replacement , *CHOICE (Psychology) , *REOPERATION , *CLINICAL medicine - Abstract
Purpose: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Methods: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Results: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Conclusion: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Radiolabeling Strategies of Nanobodies for Imaging Applications.
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Küppers J, Kürpig S, Bundschuh RA, Essler M, and Lütje S
- Abstract
Nanobodies are small recombinant antigen-binding fragments derived from camelid heavy-chain only antibodies. Due to their compact structure, pharmacokinetics of nanobodies are favorable compared to full-size antibodies, allowing rapid accumulation to their targets after intravenous administration, while unbound molecules are quickly cleared from the circulation. In consequence, high signal-to-background ratios can be achieved, rendering radiolabeled nanobodies high-potential candidates for imaging applications in oncology, immunology and specific diseases, for instance in the cardiovascular system. In this review, a comprehensive overview of central aspects of nanobody functionalization and radiolabeling strategies is provided.
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- 2021
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8. DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis-Challenges and Critical Points in Implementation into Clinical Routine.
- Author
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Meisenheimer M, Kürpig S, Essler M, and Eppard E
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- Bone Density Conservation Agents chemistry, Bone Neoplasms diagnostic imaging, Bone Neoplasms secondary, Bronchial Neoplasms diagnostic imaging, Bronchial Neoplasms pathology, Gallium Radioisotopes, Humans, Isotope Labeling, Quality Control, Zoledronic Acid chemistry, Bone Density Conservation Agents pharmacology, Bone Neoplasms drug therapy, Bronchial Neoplasms drug therapy, Heterocyclic Compounds, 1-Ring chemistry, Palliative Care, Radiopharmaceuticals chemistry, Zoledronic Acid pharmacology
- Abstract
The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory requirements turned out to be unexpectedly challenging. The scope of this work is the presentation and discussion of problems encountered during this process. Briefly, the radiolabelling process and purification, as well as the quality control published, did not meet the expectations. The constant effort setting up an automated radiolabelling procedure resulted in (a) an enhanced manual method using coated glass reactors, (b) a combination of three different reliable radio thin-layer chromatography (TLC) methods instead of the published and (c) a preliminary radio high-pressure liquid chromatography (HPLC) method for identification of the compound. Additionally, an automated radiolabelling process was developed, but it requires further improvement, e.g., in terms of a reactor vessel or purification of the crude product. The published purification method was found to be unsuitable for clinical routine, and an intense screening did not lead to a satisfactory result; here, more research is necessary. To sum up, implementation of DOTA-ZOL was possible but revealed a lot of critical points, of which not all could be resolved completely yet.
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- 2020
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9. [177Lu]Lu-DOTA-zoledronate therapy - first application in a patient with primary osseous metastatic bronchial carcinoma.
- Author
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Kreppel B, Gaertner FC, Ahmadzadehfar H, Khawar A, Roesch F, Kürpig S, Meisenheimer M, Essler M, and Bundschuh RA
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- Humans, Male, Bronchial Neoplasms drug therapy, Bronchial Neoplasms diagnostic imaging, Bronchial Neoplasms secondary, Bronchial Neoplasms radiotherapy, Organometallic Compounds therapeutic use, Middle Aged, Octreotide therapeutic use, Octreotide analogs & derivatives, Carcinoma, Bronchogenic secondary, Carcinoma, Bronchogenic drug therapy, Carcinoma, Bronchogenic radiotherapy, Carcinoma, Bronchogenic diagnostic imaging, Radiopharmaceuticals therapeutic use, Bone Neoplasms secondary, Bone Neoplasms radiotherapy, Bone Neoplasms diagnostic imaging, Bone Neoplasms drug therapy, Zoledronic Acid therapeutic use
- Abstract
Competing Interests: The authors declare that they have no conflict of interest.
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- 2020
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10. Manual vs automated 68 Ga-radiolabelling-A comparison of optimized processes.
- Author
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Meisenheimer M, Kürpig S, Essler M, and Eppard E
- Abstract
A critical factor for clinical practice is the production of
68 Ga radiopharmaceuticals manufactured manually or through an automated procedure.68 Ga radiopharmaceuticals are often prepared manually, although this method can lead to an increased operator's radiation dose and potential variability within production. The present work compares68 Ga-radiolabelling (PSMA-11; DOTA-TOC) utilizing a cassette module (GAIA; Elysia-Raytest; Germany) with a manual setup for routine clinical production with regard to process reliability and reproducibility., (© 2019 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)- Published
- 2020
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11. Biodistribution and post-therapy dosimetric analysis of [ 177 Lu]Lu-DOTA ZOL in patients with osteoblastic metastases: first results.
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Khawar A, Eppard E, Roesch F, Ahmadzadehfar H, Kürpig S, Meisenheimer M, Gaertner FC, Essler M, and Bundschuh RA
- Abstract
Background: Preclinical biodistribution and dosimetric analysis of [
177 Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177 Lu]Lu-DOTAZOL in patients with metastatic skeletal disease., Method: Four patients with metastatic skeletal disease (age range, 64-83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177 Lu]Lu-DOTAZOL . Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier's dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose., Results: Qualitative biodistribution analysis revealed early and high uptake of [177 Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177 Lu]Lu-DOTAZOL are consistent with preclinical data., Conclusion: [177 Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177 Lu]Lu-DOTAZOL in the clinical setting.- Published
- 2019
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12. Ethanol effects on 68 Ga-radiolabelling efficacy and radiolysis in automated synthesis utilizing NaCl post-processing.
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Meisenheimer M, Kürpig S, Essler M, and Eppard E
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Objective: Recent studies showed that ethanol in the reaction mixture improves radiolabelling with trivalent radiometals in terms of precursor amount, reaction time, reaction temperature and radiolysis. With regard to clinical application, this effect is of practical interest in radiopharmacy. The aim of this study was to evaluate whether the positive effect of ethanol can be exploited in automated systems utilizing NaCl-post processing., Methods: Gallium-68 was obtained from a 1.85 GBq
68 Ge/68 Ga-generator. Radiolabelling was performed on an automated68 Ga-labelling cassette module. The standard labelling protocol was used without modifications. 0-40 vol% ethanol were added to the reaction mixture. Quality control was performed using radioHPLC and radioTLC., Results: Utilization of additional ethanol on an automated cassette module can be achieved by adding ethanol directly to the buffer solution without further modifications of the standard procedure. Radiolysis was decreased significantly as analysed by radioHPLC., Conclusion: It was possible to combine the positive effects of ethanol on radiolabelling efficacy and radiolysis with the standard labelling procedure of an automated cassette module system. The whole process guarantees safe preparation of highly pure68 Ga-peptide for clinical application.- Published
- 2019
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13. Preliminary results of biodistribution and dosimetric analysis of [ 68 Ga]Ga-DOTA ZOL : a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases.
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Khawar A, Eppard E, Roesch F, Ahmadzadehfar H, Kürpig S, Meisenheimer M, Gaertner FC, Essler M, and Bundschuh RA
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- Aged, Aged, 80 and over, Bone Neoplasms secondary, Female, Humans, Male, Middle Aged, Radiometry, Retrospective Studies, Tissue Distribution, Bone Neoplasms diagnostic imaging, Bone Neoplasms metabolism, Gallium Radioisotopes, Heterocyclic Compounds, 1-Ring chemistry, Positron Emission Tomography Computed Tomography, Zoledronic Acid chemistry, Zoledronic Acid pharmacokinetics
- Abstract
Objective: Pre-clinical studies with gallium-68 zoledronate ([
68 Ga]Ga-DOTAZOL ) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [177 Lu]Lu-DOTAZOL and [225 Ac]Ac-DOTAZOL . This study aims to be the first human biodistribution and dosimetric analysis of [68 Ga]Ga-DOTAZOL ., Methods: Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190 MBq (4.05-5.14 mCi) of [68 Ga]Ga-DOTAZOL i.v. Biodistribution of [68 Ga]Ga-DOTAZOL was studied with PET/CT initial dynamic imaging for 30 min; list mode over abdomen (reconstructed as six images of 300 s) followed by static (skull to mid-thigh) imaging at 45 min and 2.5 h with Siemens Biograph 2 PET/CT camera. Also, blood samples (8 time points) and urine samples (2 time points) were collected over a period of 2.5 h. Total activity (MBq) in source organs was determined using interview fusion software (MEDISO Medical Imaging Systems, Budapest, Hungary). A blood-based method for bone marrow self-dose determination and a trapezoidal method for urinary bladder contents residence time calculation were used. OLINDA/EXM version 2.0 software (Hermes Medical Solutions, Stockholm, Sweden) was used to generate residence times for source organs, organ absorbed doses and effective doses., Results: High uptake in skeleton as target organ, kidneys and urinary bladder as organs of excretion and faint uptake in liver, spleen and salivary glands were seen. Qualitative and quantitative analysis supported fast blood clearance, high bone to soft tissue and lesion to normal bone uptake with [68 Ga]Ga-DOTAZOL . Urinary bladder with the highest absorbed dose of 0.368 mSv/MBq presented the critical organ, followed by osteogenic cells, kidneys and red marrow receiving doses of 0.040, 0.031 and 0.027 mSv/MBq, respectively. The mean effective dose was found to be 0.0174 mSv/MBq which results in an effective dose of 2.61 mSv from 150 MBq., Conclusions: Biodistribution of [68 Ga]Ga-DOTAZOL was comparable to [18 F]NaF, [99m Tc]Tc-MDP and [68 Ga]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [18 F]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [177 Lu]Lu-DOTAZOL and [225 Ac]Ac-DOTAZOL .- Published
- 2019
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14. Radionuclide intake risks in the clinical administration of 223 RaCl 2 .
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Scholl C, Bundschuh RA, Hirzebruch S, Glanert T, Wei X, Kürpig S, Rödel R, Essler M, Thomas L, and Ahmadzadehfar H
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- Humans, Male, Radioisotopes administration & dosage, Risk Assessment, Antineoplastic Agents administration & dosage, Occupational Exposure analysis, Prostatic Neoplasms, Castration-Resistant radiotherapy, Radioisotopes analysis, Radium administration & dosage
- Abstract
An intake monitoring program covering more than half a year of clinical administration of Radium-223-dichloride for the palliative treatment of castration-resistant prostate cancer was carried out in the nuclear medicine department of the university hospital Bonn. Radioactivity in a total of 87 samples of gloves, air filters, faecal bioassays and face masks was measured and evaluated to assess the need for radiation protection measures for the medical staff. The main aim was to quantify or obtain an upper limit for the intake factor. An intake factor of 10
-8 was measured when the preparation of patient doses took place in part in a laminar flow cabinet, which indicates an intake factor of 10-7 in more commonplace practice without a cabinet. The intake factor is therefore at the same level as other standard applications of unsealed sources in nuclear medicine. Our findings confirmed that masks are not required under any circumstances. However, the investigation also revealed that contamination risks, especially during the preparation of doses in syringes, should not be neglected.- Published
- 2019
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15. Outcome and safety of rechallenge [ 177 Lu]Lu-PSMA-617 in patients with metastatic prostate cancer.
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Yordanova A, Linden P, Hauser S, Meisenheimer M, Kürpig S, Feldmann G, Gaertner FC, Essler M, and Ahmadzadehfar H
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- Aged, Aged, 80 and over, Feasibility Studies, Humans, Ligands, Lutetium, Male, Middle Aged, Neoplasm Metastasis, Prostate-Specific Antigen, Retrospective Studies, Survival Analysis, Treatment Outcome, Dipeptides adverse effects, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring adverse effects, Heterocyclic Compounds, 1-Ring therapeutic use, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Safety
- Abstract
Background: Data are sparse regarding the feasibility of radioligand therapy (RLT) with [
177 Lu]Lu-PSMA-617 as a retreatment. We aimed to assess the outcome and safety of rechallenge PSMA-RLT in patients with progressive prostatic cancer who previously benefited from this therapy., Materials and Methods: Patients who received rechallenge therapy at our department from January 2015 to March 2018 were assessed. Non-haematological and haematological adverse events were evaluated from laboratory data and clinical reports and were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Time to prostate-specific-antigen (PSA) progression and the overall survival (OS) rate of the study patients were calculated from the date of the first rechallenge cycle. Furthermore, the OS calculated from the first cycle baseline PSMA-RLT was compared with the survival of patients who received only baseline PSMA-RLT. The response data were determined using [68 Ga]Ga-PSMA-PET/CT and measurements of the tumour marker PSA., Results: Included in this retrospective study were 30 patients who were initially treated with a median of 3 cycles (range 1-5) of PSMA-RLT and were eventually retreated after a median of 6 months (range 2-26). Each patient received a median of 3 (range 1-6) rechallenge cycles. None of the patients experienced a disabling or life-threatening grade 4 adverse event according to the Common Toxicity Criteria (CTC). Grade 3 toxicity occurred in 8 patients (27%). Serious adverse events included leucopoenia (n = 2), neutropoenia (n = 1), anaemia (n = 4), thrombopenia (n = 4) and elevated renal parameters (n = 1). Irreversible adverse events occurred in 21 patients (70%). The permanent adverse events were mild/moderate (CTC grade 1/2) in 19 patients and serious (CTC grade 3) in two patients, respectively. According to PSA measurements, 75-90% of patients showed a benefit (response/stable) from the first 4 rechallenge cycles. The median OS was 12 months calculated from the first rechallenge cycle and 25 months calculated from the first cycle baseline PSMA-RLT. For comparison, the median OS in patients who received only baseline PSMA-RLT was 9 months. The difference according to the logrank test was significant: p value <0.001. Patients with a PSA decrease after the first cycle of rechallenge PSMA-RLT survived a median of 19 months, while patients with a PSA increase survived only 6 months., Conclusion: Rechallenge prostate-specific membrane antigen (PSMA) therapy has an acceptable safety profile. The majority of the retreated patients benefited from the rechallenge therapy. Patients who showed a biochemical response achieved a longer OS compared to patients who did not respond. The median OS was significantly longer in patients after rechallenge PSMA-RLT than in patients who received only baseline PSMA-RLT.- Published
- 2019
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16. Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.
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Khawar A, Eppard E, Sinnes JP, Roesch F, Ahmadzadehfar H, Kürpig S, Meisenheimer M, Gaertner FC, Essler M, and Bundschuh RA
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- Aged, Carcinoma diagnostic imaging, Carcinoma pathology, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring therapeutic use, Humans, Lutetium, Male, Neoplasm Metastasis, Organometallic Compounds therapeutic use, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant diagnostic imaging, Prostatic Neoplasms, Castration-Resistant pathology, Radiopharmaceuticals therapeutic use, Radiotherapy Dosage, Scandium, Carcinoma radiotherapy, Dipeptides pharmacokinetics, Heterocyclic Compounds, 1-Ring pharmacokinetics, Organometallic Compounds pharmacokinetics, Positron Emission Tomography Computed Tomography methods, Prostatic Neoplasms, Castration-Resistant radiotherapy, Radiation Dosage, Radiopharmaceuticals pharmacokinetics, Radiotherapy Planning, Computer-Assisted methods
- Abstract
In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma., Methods: Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body., Results: The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients)., Conclusions: [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.
- Published
- 2018
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17. [44Sc]Sc-PSMA-617 Biodistribution and Dosimetry in Patients With Metastatic Castration-Resistant Prostate Carcinoma.
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Khawar A, Eppard E, Sinnes JP, Roesch F, Ahmadzadehfar H, Kürpig S, Meisenheimer M, Gaertner FC, Essler M, and Bundschuh RA
- Subjects
- Aged, Humans, Male, Neoplasm Metastasis, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant pathology, Radiation Dosage, Tissue Distribution, Dipeptides pharmacokinetics, Heterocyclic Compounds, 1-Ring pharmacokinetics, Positron Emission Tomography Computed Tomography, Prostatic Neoplasms, Castration-Resistant diagnostic imaging, Radioisotopes pharmacokinetics, Radiopharmaceuticals pharmacokinetics, Scandium pharmacokinetics
- Abstract
Aim: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients., Methods: Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection. Time-dependent changes in percentage activity in source organs (kidneys, bladder, salivary glands, small intestine, liver, spleen, and whole body) were determined. Bone marrow and urinary bladder contents residence time were also calculated. Source organs residence time, organ-absorbed doses, and effective doses were determined using OLINDA/EXM software., Results: Physiological tracer uptake was seen in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and in metastases. Kidneys with highest radiation absorbed dose of 3.19E-01 mSv/MBq were the critical organs, followed by urinary bladder wall (2.24E-01 mSv/MBq, spleen [1.85E-01], salivary glands [1.11E-01], and liver [1.07E-01] mSv/MBq). Red marrow dose was found to be 3.31E-02 mSv/MBq. The mean effective dose of 3.89E-02 mSv/MBq and effective dose of 1.95 mSv was estimated from 50 MBq (treatment planning dose) of [Sc]Sc-PSMA-617., Conclusions: [Sc]Sc-PSMA-617 is found to be a very promising radiopharmaceutical that can be used for pre [Lu]Lu-PSMA-617 therapeutic dosimetric assessment.
- Published
- 2018
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18. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [ 177 Lu]Lu-PSMA-617.
- Author
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Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kürpig S, Eppard E, Wei X, Schlenkhoff C, Hauser S, and Essler M
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Dipeptides metabolism, Heterocyclic Compounds, 1-Ring metabolism, Humans, Ligands, Male, Middle Aged, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant metabolism, Retrospective Studies, Survival Analysis, Treatment Outcome, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring therapeutic use, Lutetium therapeutic use, Prostatic Neoplasms, Castration-Resistant pathology, Prostatic Neoplasms, Castration-Resistant radiotherapy, Radioisotopes therapeutic use
- Abstract
Purpose: Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [
177 Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT., Methods: CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation., Results: Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA., Conclusion: Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.- Published
- 2017
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19. The impact of repeated cycles of radioligand therapy using [ 177 Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer.
- Author
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Yordanova A, Becker A, Eppard E, Kürpig S, Fisang C, Feldmann G, Essler M, and Ahmadzadehfar H
- Subjects
- Aged, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring therapeutic use, Humans, Ligands, Lutetium adverse effects, Male, Neoplasm Metastasis, Prostate-Specific Antigen, Prostatic Neoplasms physiopathology, Radioisotopes adverse effects, Risk Factors, Time Factors, Treatment Failure, Dipeptides adverse effects, Heterocyclic Compounds, 1-Ring adverse effects, Hormones therapeutic use, Kidney physiopathology, Kidney radiation effects, Lutetium therapeutic use, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Radioisotopes therapeutic use
- Abstract
Background: [
177 Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring., Methods: Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [177 Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values., Results: None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C., Conclusion: Renal toxicity in patients treated with [177 Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.- Published
- 2017
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20. Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer.
- Author
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Gaertner FC, Halabi K, Ahmadzadehfar H, Kürpig S, Eppard E, Kotsikopoulos C, Liakos N, Bundschuh RA, Strunk H, and Essler M
- Abstract
Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load., Results: In patients with high tumor load, SUV
mean was reduced to 61.5% in the lacrimal glands, to 56.6% in the parotid glands, to 63.7% in the submandibular glands, to 61.3% in the sublingual glands and to 55.4% in the kidneys ( p < 0.001). Further significant differences were observed for brain, mediastinum, liver, spleen and muscle. Total tracer retention was higher in patients with high tumor load ( p < 0.05). SUV in lacrimal, salivary glands and kidneys correlated negatively with PSA., Materials and Methods: 135 patients were retrospectively evaluated. SUV was measured in the lacrimal and salivary glands, brain, heart, liver, spleen, kidneys, muscle and bone. SUV was correlated with visual tumor load, total tracer retention and PSA., Conclusions: Patients with high tumor load show a significant reduction of tracer uptake in dose-limiting organs. As similar effects might occur when performing RLT using Lu-177-labeled PSMA-ligands, individual adaptations of therapy protocols based on diagnostic PSMA PET imaging before therapy might help to further increase efficacy and safety of RLT., Competing Interests: CONFLICTS OF INTEREST RAB has a non-commercial research contract with and has received a speaker honorarium from Mediso Medical Imaging Systems Ltd., Budapest, Hungary. ME is a consultant to Bayer, Novartis, Eisai and Ipsen.- Published
- 2017
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21. 68 Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with 223 Ra: Proof of Concept.
- Author
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Ahmadzadehfar H, Azgomi K, Hauser S, Wei X, Yordanova A, Gaertner FC, Kürpig S, Strunk H, and Essler M
- Subjects
- Aged, Bone Neoplasms diagnostic imaging, Edetic Acid analogs & derivatives, Gallium Isotopes, Gallium Radioisotopes, Humans, Male, Oligopeptides, Prognosis, Prostatic Neoplasms radiotherapy, Radioisotopes therapeutic use, Radiopharmaceuticals therapeutic use, Radiotherapy Dosage, Radiotherapy, Image-Guided methods, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Treatment Outcome, Bone Neoplasms radiotherapy, Bone Neoplasms secondary, Organometallic Compounds, Positron-Emission Tomography methods, Prostatic Neoplasms diagnostic imaging, Radium therapeutic use
- Abstract
We retrospectively evaluated the utility of
68 Ga-PSMA-11 PET for planning223 RaCl2 therapy of patients with metastatic prostate cancer and its impact on the therapeutic response as determined by prostate-specific antigen (PSA) and alkaline phosphatase (ALP), as well as the correlation of PSA changes with the results of prostate-specific membrane antigen (PSMA) PET follow-up scans. Methods: Sixty-three patients with a median age of 73 y who underwent 307 cycles of therapy with223 RaCl2 were analyzed. In 31 patients, bone scanning and radiologic imaging were performed for pretherapeutic imaging (group 1). In 32 patients, bone scanning and PSMA PET were performed before therapy (group 2). Patients with small lymph node metastases and local recurrence were not excluded from treatment, consistent with current guidelines. PSA and ALP were measured before each treatment cycle and 4 wk after the final cycle. Thirteen patients from group 2, who underwent a second PSMA PET scan as a follow-up, were evaluated to determine the significance of PSA changes as a follow-up marker. Results: In group 1, 4 patients (12.9%) showed a PSA decline, of whom 2 patients and 1 patient showed a PSA decline of more than 30% and more than 50%, respectively. In contrast, in group 2, 14 patients (43.8%) showed a PSA decline, of whom 10 and 8 patients showed a decline of more than 30% and more than 50%, respectively ( P = 0.007). Thirty-seven patients had a high ALP level (19 from group 1 and 18 from group 2). Twelve (63.2%) and 16 (88.9%) patients in groups 1 and 2, respectively, showed an ALP decline. This difference was not significant; however, 7 (36%) and 13 (72.2%) patients in groups 1 and 2, respectively, showed an ALP decline of more than 30% ( P = 0.04). Considering any ALP decline as a response, no patient with increasing ALP showed a PSA response ( P = 0.036). There was a significant correlation between the PSA changes and the therapeutic response according to follow-up PSMA PET. Conclusion: When PSMA PET is used as the gatekeeper in addition to bone scanning, radionuclide therapy with223 Ra may be more effective and have more success regarding changes in the PSA. An increase in PSA during therapy cycles occurs because of disease progression., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2017
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22. Radioligand therapy of metastatic prostate cancer using 177 Lu-PSMA-617 after radiation exposure to 223 Ra-dichloride.
- Author
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Ahmadzadehfar H, Zimbelmann S, Yordanova A, Fimmers R, Kürpig S, Eppard E, Gaertner FC, Wei X, Hauser S, and Essler M
- Abstract
Radioligand therapy with
177 Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with223 Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of177 Lu-PSMA-617 after exposure to more cycles of223 Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with223 Ra. Group 1 included 20 patients, who had received therapy with223 Ra prior to Lu-PSMA-617 therapy. Group 2, which was the control group regarding hematotoxicity, comprised 29 patients without any history of a bone-targeted radionuclide therapy. No CTC 4° hematotoxicity was observed in the entire study population. There was no CTC 3° or CTC 4° leucopenia in either group. One and three patients from group 1 and 2, respectively, showed CTC 3° anemia. In group 1 there was significantly more CTC 2° anemia (50% vs. 6.9%) (p=0.008). One patient from group 1 (5%) showed a CTC 3° thrombocytopenia without any concurrent anemia, and two patients from group 2 (7%) showed a CTC 3° thrombocytopenia, one with CTC 3° anemia and one without any anemia. There were no significant differences between the two groups regarding leucopenia and thrombocytopenia. These results confirmed that performing repeated cycles of Lu-PSMA-617 after223 Ra seems to be safe with a very small probability of hematotoxicity., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no financial or nonfinancial competing interests.- Published
- 2017
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23. Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with 177Lu-PSMA-617.
- Author
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Ferdinandus J, Eppard E, Gaertner FC, Kürpig S, Fimmers R, Yordanova A, Hauser S, Feldmann G, Essler M, and Ahmadzadehfar H
- Subjects
- Aged, Biomarkers, Tumor blood, Carcinoma blood, Humans, Lutetium, Male, Prognosis, Prostatic Neoplasms, Castration-Resistant diagnosis, Radiopharmaceuticals therapeutic use, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Treatment Outcome, Carcinoma radiotherapy, Carcinoma secondary, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring therapeutic use, Prostate-Specific Antigen blood, Prostatic Neoplasms, Castration-Resistant blood, Prostatic Neoplasms, Castration-Resistant radiotherapy
- Abstract
Radioligand therapy (RLT) with
177 Lu-PSMA-617 (PSMA is prostate-specific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. In this study, we evaluated the effect of different pretherapeutic parameters on the therapeutic response measured by prostate-specific antigen (PSA) 2 mo after RLT., Methods: RLT was performed in 40 hormone-refractory patients with distant metastases and progressive disease (mean age, 71.4 y).68 Ga-PSMA-11 PET/CT was performed in all patients 1-2 wk before RLT. All patients were treated with a mean of 6 GBq. The SUVmax of tumor lesions was determined using region-of-interest analysis. Complete blood counts, renal and liver function assessments, previous therapies, pain medication, and SUVs were included in the analysis. PSA was assessed 2 mo after RLT., Results: In the univariate analysis, younger age, higher levels of γ-glutamyl transferase, lower pretherapeutic hemoglobin, a higher Gleason score, a higher number of platelets, higher C-reactive protein, regular need for pain medication, and higher lactate dehydrogenase had a negative impact on the therapeutic response; however, the multivariate analysis revealed that the most significant independent factors were the number of platelets and regular need for pain medication. The response was independent of the amount of PSMA uptake as well as previous therapies and other measured factors., Conclusion: A PSA decline of more than 50% was observed significantly more in patients without a regular need for analgesics., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2017
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24. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer.
- Author
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Ahmadzadehfar H, Eppard E, Kürpig S, Fimmers R, Yordanova A, Schlenkhoff CD, Gärtner F, Rogenhofer S, and Essler M
- Subjects
- Aged, Aged, 80 and over, Humans, Lutetium administration & dosage, Lutetium chemistry, Male, Middle Aged, Positron Emission Tomography Computed Tomography, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant diagnostic imaging, Prostatic Neoplasms, Castration-Resistant pathology, Radioisotopes administration & dosage, Radioisotopes chemistry, Retrospective Studies, Dipeptides administration & dosage, Heterocyclic Compounds, 1-Ring administration & dosage, Organometallic Compounds administration & dosage, Peptides administration & dosage, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant radiotherapy, Radiopharmaceuticals therapeutic use
- Abstract
Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64-82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17-2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients.
- Published
- 2016
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25. Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study.
- Author
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Ahmadzadehfar H, Rahbar K, Kürpig S, Bögemann M, Claesener M, Eppard E, Gärtner F, Rogenhofer S, Schäfers M, and Essler M
- Abstract
Background: Radioligand therapy (RLT) with (177)Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments., Methods: RLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). (68)Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5-853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1-6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes., Results: Eight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4)., Conclusions: Our initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.
- Published
- 2015
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