Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy
Abstract Background In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to...
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SpringerOpen
2025-01-01
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| Series: | EJNMMI Research |
| Online Access: | https://doi.org/10.1186/s13550-024-01190-7 |
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| author | Jan Heilinger Katrin Sabine Roth Henning Weis Antonis Fink Jasmin Weindler Felix Dietlein Philipp Krapf Klaus Schomäcker Bernd Neumaier Markus Dietlein Alexander Drzezga Carsten Kobe |
| author_facet | Jan Heilinger Katrin Sabine Roth Henning Weis Antonis Fink Jasmin Weindler Felix Dietlein Philipp Krapf Klaus Schomäcker Bernd Neumaier Markus Dietlein Alexander Drzezga Carsten Kobe |
| author_sort | Jan Heilinger |
| collection | DOAJ |
| description | Abstract Background In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different 18F-labeled PSMA ligands to today’s standard radiopharmaceutical 68Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach. Results Differences in background activity among different PSMA-PET tracers lead to variations in tumor-to-background ratios (TBR). In [18F]F-DCFPyL-PET, TBR with the liver as the reference organ (TBRliver) was comparable to [68Ga]Ga-PSMA-11-PET, while [18F]F-PSMA-1007-PET and [18F]F-JK-PSMA-7-PET showed significantly lower values. Using the parotid gland as the reference (TBRparotidgland), [18F]F-DCFPyL-PET exhibited significantly higher values, whereas [18F]F-PSMA-1007-PET and [18F]F-JK-PSMA-7-PET were comparable. For the spleen (TBRspleen), [18F]F-JK-PSMA-7-PET was comparable, but [18F]F-DCFPyL-PET and [18F]F-PSMA-1007-PET showed significantly higher and lower values, respectively. An additional Bland-Altman analyses revealed low bias for [18F]F-DCFPyL-PET in TBRparotidgland, whereas significant differences in TBRliver and TBRspleen for the other tracers resulted in higher bias. Conclusion Different PSMA-PET tracers exhibit distinct biodistribution patterns, leading to variations in tumor-to-background ratios (TBR) in reference organs such as the liver, parotid gland, and spleen. Patient selection for PSMA-directed radioligand therapy is currently based on a semiquantitative approach using the liver as a reference region in [68Ga]Ga-PSMA-11-PET. Thus, the use of alternative [18F]-labeled tracers may result in under- or overestimation of a patient’s suitability for therapy. This highlights the importance of a comprehensive understanding of the differences in tracer-specific uptake behavior for accurate decisions regarding PSMA-expression levels. However, as the patient cohort in this study is at earlier disease stages, the generalizability of these findings to later-stage patients remains unclear and requires further investigation. |
| format | Article |
| id | doaj-art-6e40440f3f174804b75da0255d55e0ee |
| institution | Kabale University |
| issn | 2191-219X |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-6e40440f3f174804b75da0255d55e0ee2025-01-12T12:39:23ZengSpringerOpenEJNMMI Research2191-219X2025-01-011511810.1186/s13550-024-01190-7Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapyJan Heilinger0Katrin Sabine Roth1Henning Weis2Antonis Fink3Jasmin Weindler4Felix Dietlein5Philipp Krapf6Klaus Schomäcker7Bernd Neumaier8Markus Dietlein9Alexander Drzezga10Carsten Kobe11Department of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneInstitute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbHDepartment of Nuclear Medicine, University Hospital of CologneInstitute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbHDepartment of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneDepartment of Nuclear Medicine, University Hospital of CologneAbstract Background In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different 18F-labeled PSMA ligands to today’s standard radiopharmaceutical 68Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach. Results Differences in background activity among different PSMA-PET tracers lead to variations in tumor-to-background ratios (TBR). In [18F]F-DCFPyL-PET, TBR with the liver as the reference organ (TBRliver) was comparable to [68Ga]Ga-PSMA-11-PET, while [18F]F-PSMA-1007-PET and [18F]F-JK-PSMA-7-PET showed significantly lower values. Using the parotid gland as the reference (TBRparotidgland), [18F]F-DCFPyL-PET exhibited significantly higher values, whereas [18F]F-PSMA-1007-PET and [18F]F-JK-PSMA-7-PET were comparable. For the spleen (TBRspleen), [18F]F-JK-PSMA-7-PET was comparable, but [18F]F-DCFPyL-PET and [18F]F-PSMA-1007-PET showed significantly higher and lower values, respectively. An additional Bland-Altman analyses revealed low bias for [18F]F-DCFPyL-PET in TBRparotidgland, whereas significant differences in TBRliver and TBRspleen for the other tracers resulted in higher bias. Conclusion Different PSMA-PET tracers exhibit distinct biodistribution patterns, leading to variations in tumor-to-background ratios (TBR) in reference organs such as the liver, parotid gland, and spleen. Patient selection for PSMA-directed radioligand therapy is currently based on a semiquantitative approach using the liver as a reference region in [68Ga]Ga-PSMA-11-PET. Thus, the use of alternative [18F]-labeled tracers may result in under- or overestimation of a patient’s suitability for therapy. This highlights the importance of a comprehensive understanding of the differences in tracer-specific uptake behavior for accurate decisions regarding PSMA-expression levels. However, as the patient cohort in this study is at earlier disease stages, the generalizability of these findings to later-stage patients remains unclear and requires further investigation.https://doi.org/10.1186/s13550-024-01190-7 |
| spellingShingle | Jan Heilinger Katrin Sabine Roth Henning Weis Antonis Fink Jasmin Weindler Felix Dietlein Philipp Krapf Klaus Schomäcker Bernd Neumaier Markus Dietlein Alexander Drzezga Carsten Kobe Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy EJNMMI Research |
| title | Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy |
| title_full | Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy |
| title_fullStr | Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy |
| title_full_unstemmed | Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy |
| title_short | Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy |
| title_sort | do you know your psma tracer variability in the biodistribution of different psma ligands and its potential impact on defining psma positivity prior to psma targeted therapy |
| url | https://doi.org/10.1186/s13550-024-01190-7 |
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