@article{BluemelLinkeHerrmannetal.2016,
  author    = {Bluemel, Christina and Linke, Fraenze and Herrmann, Ken and Simunovic, Iva and Eiber, Matthias and Kestler, Christian and Buck, Andreas K. and Schirbel, Andreas and Bley, Thorsten A. and Wester, Hans-Juergen and Vergho, Daniel and Becker, Axel},
  title     = {Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy},
  series = {EJNMMI Research},
  volume    = {6},
  journal   = {EJNMMI Research},
  number    = {78},
  doi       = {10.1186/s13550-016-0233-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147798},
  year      = {2016},
  abstract  = {Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 \%) patients. In 62.5 \% of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 \%) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 \%) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 \%) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 \% of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.},
  language  = {en}
}
@article{BreunMonoranuKessleretal.2019,
  author    = {Breun, Maria and Monoranu, Camelia M. and Kessler, Almuth F. and Matthies, Cordula and L{\"o}hr, Mario and Hagemann, Carsten and Schirbel, Andreas and Rowe, Steven P. and Pomper, Martin G. and Buck, Andreas K. and Wester, Hans-J{\"u}rgen and Ernestus, Ralf-Ingo and Lapa, Constantin},
  title     = {[\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas},
  series = {Frontiers in Oncology},
  volume    = {9},
  journal   = {Frontiers in Oncology},
  number    = {503},
  doi       = {10.3389/fonc.2019.00503},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201863},
  year      = {2019},
  abstract  = {We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor. Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients. Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors. Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.},
  language  = {en}
}
@article{BrumbergBecklDierksetal.2020,
  author    = {Brumberg, Joachim and Beckl, Melanie and Dierks, Alexander and Schirbel, Andreas and Krebs, Markus and Buck, Andreas and K{\"u}bler, Hubert and Lapa, Constantin and Seitz, Anna Katharina},
  title     = {Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy},
  series = {Biomedicines},
  volume    = {8},
  journal   = {Biomedicines},
  number    = {11},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines8110511},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219301},
  year      = {2020},
  abstract  = {Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7\% vs. 72.6\%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.},
  language  = {en}
}
@article{BuckSerflingLindneretal.2022,
  author    = {Buck, Andreas K. and Serfling, Sebastian E. and Lindner, Thomas and H{\"a}nscheid, Heribert and Schirbel, Andreas and Hahner, Stefanie and Fassnacht, Martin and Einsele, Hermann and Werner, Rudolf A.},
  title     = {CXCR4-targeted theranostics in oncology},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  doi       = {10.1007/s00259-022-05849-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324545},
  pages     = {4133-4144},
  year      = {2022},
  abstract  = {A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.},
  language  = {en}
}
@article{BuderLapaKreissletal.2014,
  author    = {Buder, Kristina and Lapa, Constantin and Kreissl, Michael C. and Schirbel, Andreas and Herrmann, Ken and Schnack, Alexander and Br{\"o}cker, Eva-Bettina and Goebeler, Matthias and Buck, Andreas K. and Becker, J{\"u}rgen C.},
  title     = {"Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging"},
  doi       = {10.1186/1471-2407-14-268},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110326},
  year      = {2014},
  abstract  = {Background Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment. Methods To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT). Results SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73\% for nodal metastases, 100\% for bone, and 67\% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17\%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13\%). Conclusion SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.},
  language  = {en}
}
@article{ChifuHeinzeFussetal.2020,
  author    = {Chifu, Irina and Heinze, Britta and Fuss, Carmina T. and Lang, Katharina and Kroiss, Matthias and Kircher, Stefan and Ronchi, Cristina L. and Altieri, Barbara and Schirbel, Andreas and Fassnacht, Martin and Hahner, Stefanie},
  title     = {Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma},
  series = {Frontiers in Endocrinology},
  volume    = {11},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2020.597878},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216494},
  year      = {2020},
  abstract  = {Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. However, their clinical and prognostic significance in adrenocortical carcinoma (ACC) is unknown. The aim of this study was to evaluate the chemokine receptor profile in ACC and to analyse its association with clinicopathological characteristics and clinical outcome. A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. These results were correlated with clinicopathological parameters and survival outcome. We detected strong membrane expression of CXCR4 and CXCR7 in 50\% of ACC samples. Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries (p=0.01) and local recurrences (p=0.04). CXCR4 membrane staining positively correlated with proliferation index Ki67 (r=0.17, p=0.028). CXCR7 membrane staining negatively correlated with Ki67 (r=-0.254, p=0.03) but positively with tumor size (r=0.3, p=0.02). No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy.},
  language  = {en}
}
@article{DetomasAltieriSchloetelburgetal.2021,
  author    = {Detomas, Mario and Altieri, Barbara and Schl{\"o}telburg, Wiebke and Appenzeller, Silke and Schlaffer, Sven and Coras, Roland and Schirbel, Andreas and Wild, Vanessa and Kroiss, Matthias and Sbiera, Silviu and Fassnacht, Martin and Deutschbein, Timo},
  title     = {Case Report: Consecutive Adrenal Cushing's Syndrome and Cushing's Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations},
  series = {Frontiers in Endocrinology},
  volume    = {12},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2021.731579},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244596},
  year      = {2021},
  abstract  = {The occurrence of different subtypes of endogenous Cushing's syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing's disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.},
  language  = {en}
}
@article{HartrampfHeinrichSeitzetal.2020,
  author    = {Hartrampf, Philipp E. and Heinrich, Marieke and Seitz, Anna Katharina and Brumberg, Joachim and Sokolakis, Ioannis and Kalogirou, Charis and Schirbel, Andreas and K{\"u}bler, Hubert and Buck, Andreas K. and Lapa, Constantin and Krebs, Markus},
  title     = {Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy — Do Different Software Solutions Deliver Comparable Results?},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9051390},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205893},
  year      = {2020},
  abstract  = {(1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: \(^{68}\)Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland-Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible.},
  language  = {en}
}
@article{HartrampfSeitzWeinzierletal.2022,
  author    = {Hartrampf, Philipp E. and Seitz, Anna Katharina and Weinzierl, Franz-Xaver and Serfling, Sebastian E. and Schirbel, Andreas and Rowe, Steven P. and K{\"u}bler, Hubert and Buck, Andreas K. and Werner, Rudolf A.},
  title     = {Baseline clinical characteristics predict overall survival in patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I\&T during long-term follow-up},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  doi       = {10.1007/s00259-022-05853-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324573},
  pages     = {4262-4270},
  year      = {2022},
  abstract  = {Background Radioligand therapy (RLT) with \(^{177}\)Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [\(^{177}\)Lu]Lu-PSMA I\&T RLT in a long-term follow-up. Materials and methods Ninety-two mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I\&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (interval\(_{Diagnosis-RLT}\), per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan-Meier analyses. Results Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95\% CI 1.02-1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95\% CI 1.01-1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95\% CI 1.06-1.26; P = 0.001), and interval\(_{Diagnosis-RLT}\) (HR, 0.95, 95\% CI 0.91-0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and interval\(_{Diagnosis-RLT}\), 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan-Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged interval\(_{Diagnosis-RLT}\) (P ≤ 0.01, respectively). Conclusion In mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I\&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [\(^{177}\)Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.},
  language  = {en}
}
@article{HartrampfWeinzierlBucketal.2022,
  author    = {Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Buck, Andreas K. and Rowe, Steven P. and Higuchi, Takahiro and Seitz, Anna Katharina and K{\"u}bler, Hubert and Schirbel, Andreas and Essler, Markus and Bundschuh, Ralph A. and Werner, Rudolf A.},
  title     = {Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I\&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {9},
  doi       = {10.1007/s00259-022-05744-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324581},
  pages     = {3269-3276},
  year      = {2022},
  abstract  = {Background Labelled with lutetium-177, the urea-based small molecules PSMA I\&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I\&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8\%) for [\(^{177}\)Lu]Lu-PSMA I\&T and five (9.1\%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9\%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I\&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.},
  language  = {en}
}