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18. CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors—a comprehensive analysis of imaging findings and comparison with histopathology.

Author

Dreher, Niklas, Hahner, Stefanie, Fuß, Carmina T., Schlötelburg, Wiebke, Hartrampf, Philipp E., Serfling, Sebastian E., Schirbel, Andreas, Samnick, Samuel, Higuchi, Takahiro, Weich, Alexander, Lapa, Constantin, Rosenwald, Andreas, Buck, Andreas K., Kircher, Stefan, and Werner, Rudolf A.

Subjects
POSITRON emission tomography, IMAGE analysis, SMALL cell lung cancer
Abstract

Background: C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings. Methods: A total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients' tumor tissue and investigated possible correlations with SUVmax (by providing Spearman's rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10). Results: One hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05–24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort. Conclusions: In a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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21. CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors—a comprehensive analysis of imaging findings and comparison with histopathology

Author

Dreher, Niklas, primary, Hahner, Stefanie, additional, Fuß, Carmina T., additional, Schlötelburg, Wiebke, additional, Hartrampf, Philipp E., additional, Serfling, Sebastian E., additional, Schirbel, Andreas, additional, Samnick, Samuel, additional, Higuchi, Takahiro, additional, Weich, Alexander, additional, Lapa, Constantin, additional, Rosenwald, Andreas, additional, Buck, Andreas K., additional, Kircher, Stefan, additional, and Werner, Rudolf A., additional

Published
2023
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23. 68Ga-PSMA I&T PET/CT for primary staging of prostate cancer

Author

Cytawa, Wojciech, Seitz, Anna Katharina, Kircher, Stefan, Fukushima, Kazuhito, Tran-Gia, Johannes, Schirbel, Andreas, Bandurski, Tomasz, Lass, Piotr, Krebs, Markus, Połom, Wojciech, Matuszewski, Marcin, Wester, Hans-Jürgen, Buck, Andreas K., Kübler, Hubert, and Lapa, Constantin

Published
2020
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24. Biodistribution and Radiation Dosimetry for a Probe Targeting Prostate-Specific Membrane Antigen for Imaging and Therapy

Author

Herrmann, Ken, Bluemel, Christina, Weineisen, Martina, Schottelius, Margret, Wester, Hans-Jürgen, Czernin, Johannes, Eberlein, Uta, Beykan, Seval, Lapa, Constantin, Riedmiller, Hubertus, Krebs, Markus, Kropf, Saskia, Schirbel, Andreas, Buck, Andreas K, and Lassmann, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prostate Cancer, Urologic Diseases, Biomedical Imaging, Bioengineering, Cancer, Aged, Antigens, Surface, Bone Marrow, Edetic Acid, Gallium Isotopes, Gallium Radioisotopes, Glutamate Carboxypeptidase II, Humans, Kidney, Male, Middle Aged, Oligopeptides, Positron-Emission Tomography, Prostatic Neoplasms, Radiometry, Radiopharmaceuticals, Salivary Glands, Spleen, Tissue Distribution, Whole Body Imaging, PET, PSMA, Ga-68, dosimetry, prostate cancer, 68Ga, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

UnlabelledProstate-specific membrane antigen (PSMA) is a promising target for diagnosis and treatment of prostate cancer. EuK-Subkff-(68)Ga-DOTAGA ((68)Ga-PSMA Imaging & Therapy [PSMA I&T]) is a recently introduced PET tracer for imaging PSMA expression in vivo. Whole-body distribution and radiation dosimetry of this new probe were evaluated.MethodsFive patients with a history of prostate cancer were injected intravenously with 91-148 MBq of (68)Ga-PSMA I&T (mean ± SD, 128 ± 23 MBq). After an initial series of rapid whole-body scans, 3 static whole-body scans were acquired at 1, 2, and 4 h after tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM.ResultsInjection of 150 MBq of (68)Ga-PSMA I&T resulted in an effective dose of 3.0 mSv. The kidneys were the critical organ (33 mGy), followed by the urinary bladder wall and spleen (10 mGy each), salivary glands (9 mGy each), and liver (7 mGy).Conclusion(68)Ga-PSMA I&T exhibits a favorable dosimetry, delivering organ doses that are comparable to (kidneys) or lower than those delivered by (18)F-FDG.

Published
2015

25. Radiopharmaceuticals for Treatment of Adrenocortical Carcinoma.

Author

Michalski, Kerstin, Schlötelburg, Wiebke, Hartrampf, Philipp E., Kosmala, Aleksander, Buck, Andreas K., Hahner, Stefanie, and Schirbel, Andreas

Subjects
CHEMOKINE receptors, RADIOPHARMACEUTICALS, DRUG target, NUCLEAR medicine, CARCINOMA, CANCER invasiveness
Abstract

Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [123/131I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients.

Author

Cytawa, Wojciech, Hendel, Robin, Tomasik, Bartłomiej, Weinzierl, Franz-Xaver, Bley, Thorsten, Jassem, Jacek, Schirbel, Andreas, Buck, Andreas K., Bundschuh, Ralph A., Hartrampf, Philipp E., Werner, Rudolf A., and Lapa, Constantin

Subjects
CASTRATION-resistant prostate cancer, PROSTATE cancer patients, LUTEINIZING hormone releasing hormone, PATIENT experience, LUTETIUM compounds
Abstract

Purpose: The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. Methods: This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2–9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). Results: After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1–5) and 2 (1–6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). Conclusion: In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome. [ABSTRACT FROM AUTHOR]

Published
2023
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27. CXCR4-Directed Imaging and Endoradiotherapy in Desmoplastic Small Round Cell Tumors.

Author

Hartlapp, Ingo, Hartrampf, Philipp E., Serfling, Sebastian E., Wild, Vanessa, Weich, Alexander, Rasche, Leo, Roth, Sabine, Rosenwald, Andreas, Mihatsch, Patrick W., Hendricks, Anne, Wiegering, Armin, Wiegering, Verena, Hänscheid, Heribert, Schirbel, Andreas, Werner, Rudolf A., Buck, Andreas K., Wester, Hans-Jürgen, Einsele, Hermann, Kunzmann, Volker, and Lapa, Constantin

Published
2023
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30. Impact of 68Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors

Author

Kosmala, Aleksander, primary, Serfling, Sebastian E., additional, Schlötelburg, Wiebke, additional, Lindner, Thomas, additional, Michalski, Kerstin, additional, Schirbel, Andreas, additional, Higuchi, Takahiro, additional, Hartrampf, Philipp E., additional, Buck, Andreas K., additional, Weich, Alexander, additional, and Werner, Rudolf A., additional

Published
2022
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32. Reduced splenic uptake on (68)Ga-Pentixafor-PET/CT imaging in multiple myeloma - a potential imaging biomarker for disease prognosis

Author

Kraus, Sabrina, Klassen, Philipp, Kircher, Malte, Dierks, Alexander, Habringer, Stefan, Gäble, Alexander, Kortüm, Klaus Martin, Weinhold, Niels, Ademaj-Kospiri, Valëza, Werner, Rudolf A, Schirbel, Andreas, Buck, Andreas K, Herhaus, Peter, Wester, Hans-Jürgen, Rosenwald, Andreas, Weber, Wolfgang A, Einsele, Hermann, Keller, Ulrich, Rasche, Leo, and Lapa, Constantin

Subjects
Cancer Research, Medicine (miscellaneous), ddc:610, Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Abstract

Beyond being a key factor for tumor growth and metastasis in human cancer, C-X-C motif chemokine receptor 4 (CXCR4) is also highly expressed by a number of immune cells, allowing for non-invasive read-out of inflammatory activity. With two recent studies reporting on prognostic implications of the spleen signal in diffusion-weighted magnetic resonance imaging in patients with plasma cell dyscrasias, the aim of this study was to correlate splenic (68)Ga-Pentixafor uptake in multiple myeloma (MM) with clinical parameters and to evaluate its prognostic impact. METHODS: Eighty-seven MM patients underwent molecular imaging with (68)Ga-Pentixafor-PET/CT. Splenic CXCR4 expression was semi-quantitatively assessed by peak standardized uptake values (SUV(peak)) and corresponding spleen-to-bloodpool ratios (TBR) and correlated with clinical and prognostic features as well as survival parameters. RESULTS: (68)Ga-Pentixafor-PET/CT was visually positive in all MM patients with markedly heterogeneous tracer uptake in the spleen. CXCR4 expression determined by (68)Ga-Pentixafor-PET/CT corresponded with advanced disease and was inversely associated with the number of previous treatment lines as compared to controls or untreated smouldering multiple myeloma patients (SUV(peak)Spleen 4.06 ± 1.43 vs. 6.02 ± 1.16 vs. 7.33 ± 1.40; (P5.79 ((P

Published
2022

34. CXCR4 expression of multiple myeloma as a dynamic process: influence of therapeutic agents

Author

Bögelein, Anna, primary, Stolzenburg, Antje, additional, Eiring, Patrick, additional, Lückerath, Katharina, additional, Munawar, Umair, additional, Werner, Rudolf, additional, Schirbel, Andreas, additional, Samnick, Samuel, additional, Kortüm, Klaus Martin, additional, Sauer, Markus, additional, Lapa, Constantin, additional, and Buck, Andreas K., additional

Published
2022
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35. Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Author

Heinze, Britta, Fuss, Carmina T., Mulatero, Paolo, Beuschlein, Felix, Reincke, Martin, Mustafa, Mona, Schirbel, Andreas, Deutschbein, Timo, Williams, Tracy Ann, Rhayem, Yara, Quinkler, Marcus, Rayes, Nada, Monticone, Silvia, Wild, Vanessa, Gomez-Sanchez, Celso E., Reis, Anna-Carinna, Petersenn, Stephan, Wester, Hans-Juergen, Kropf, Saskia, Fassnacht, Martin, Lang, Katharina, Herrmann, Ken, Buck, Andreas K., Bluemel, Christina, and Hahner, Stefanie

Published
2018
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37. C-X-C Motif Chemokine Receptor 4–Targeted Radioligand Therapy in Patients with Advanced T-Cell Lymphoma

Author

Buck, Andreas K., primary, Grigoleit, Götz Ulrich, additional, Kraus, Sabrina, additional, Schirbel, Andreas, additional, Heinsch, Michael, additional, Dreher, Niklas, additional, Higuchi, Takahiro, additional, Lapa, Constantin, additional, Hänscheid, Heribert, additional, Samnick, Samuel, additional, Einsele, Hermann, additional, Serfling, Sebastian E., additional, and Werner, Rudolf A., additional

Published
2022
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38. Associations between Normal Organs and Tumor Burden in Patients Imaged with Fibroblast Activation Protein Inhibitor-Directed Positron Emission Tomography

Author

Kosmala, Aleksander, primary, Serfling, Sebastian E., additional, Dreher, Niklas, additional, Lindner, Thomas, additional, Schirbel, Andreas, additional, Lapa, Constantin, additional, Higuchi, Takahiro, additional, Buck, Andreas K., additional, Weich, Alexander, additional, and Werner, Rudolf A., additional

Published
2022
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39. USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K

Author

Prieto‐Garcia, Cristian, primary, Hartmann, Oliver, additional, Reissland, Michaela, additional, Braun, Fabian, additional, Bozkurt, Süleyman, additional, Pahor, Nikolett, additional, Fuss, Carmina, additional, Schirbel, Andreas, additional, Schülein‐Völk, Christina, additional, Buchberger, Alexander, additional, Calzado Canale, Marco A., additional, Rosenfeldt, Mathias, additional, Dikic, Ivan, additional, Münch, Christian, additional, and Diefenbacher, Markus E., additional

Published
2022
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40. Author response for 'USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K'

Author

null Prieto-Garcia, Cristian, null Hartmann, Oliver, null Reissland, Michaela, null Braun, Fabian, null Bozkurt, Suleyman, null Pahor, Nikolett, null Fuss, Carmina, null Schirbel, Andreas, null Schuelein-Voelk, Christina, null Buchberger, Alexander, null Canale, Marco A. Calzado, null Rosenfeldt, Mathias, null Dikic, Ivan, null Muench, Christian, and null Diefenbacher, Markus E.

Published
2022

45. Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms using 68Ga-PentixaFor PET

Author

Buck, Andreas K., primary, Haug, Alexander, additional, Dreher, Niklas, additional, Lambertini, Alessandro, additional, Higuchi, Takahiro, additional, Lapa, Constantin, additional, Weich, Alexander, additional, Pomper, Martin G., additional, Wester, Hans-Jürgen, additional, Zehnder, Anja, additional, Schirbel, Andreas, additional, Samnick, Samuel, additional, Hacker, Marcus, additional, Pichler, Verena, additional, Hahner, Stefanie, additional, Fassnacht, Martin, additional, Einsele, Hermann, additional, Serfling, Sebastian, additional, and Werner, Rudolf A, additional

Published
2022
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46. Reduced splenic uptake on 68Ga-Pentixafor-PET/CT imaging in multiple myeloma - a potential imaging biomarker for disease prognosis

Author

Kraus, Sabrina, primary, Klassen, Philipp, additional, Kircher, Malte, additional, Dierks, Alexander, additional, Habringer, Stefan, additional, Gäble, Alexander, additional, Kortüm, Klaus Martin, additional, Weinhold, Niels, additional, Ademaj-Kospiri, Valëza, additional, Werner, Rudolf A, additional, Schirbel, Andreas, additional, Buck, Andreas K, additional, Herhaus, Peter, additional, Wester, Hans-Jürgen, additional, Rosenwald, Andreas, additional, Weber, Wolfgang A, additional, Einsele, Hermann, additional, Keller, Ulrich, additional, Rasche, Leo, additional, and Lapa, Constantin, additional

Published
2022
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49. Targeting 11-Beta Hydroxylase With [131I]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma

Author

Hahner, Stefanie, primary, Hartrampf, Philipp E, additional, Mihatsch, Patrick W, additional, Nauerz, Marc, additional, Heinze, Britta, additional, Hänscheid, Heribert, additional, Teresa Fuß, Carmina, additional, Werner, Rudolf A, additional, Pamporaki, Christina, additional, Kroiss, Matthias, additional, Fassnacht, Martin, additional, Buck, Andreas K, additional, and Schirbel, Andreas, additional

Published
2021
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