TY  - JOUR
A1  - Lapa, Constantin
A1  - Herrmann, Ken
A1  - Schirbel, Andreas
A1  - Hänscheid, Heribert
A1  - Lückerath, Katharina
A1  - Schottelius, Margret
A1  - Kircher, Malte
A1  - Werner, Rudolf A.
A1  - Schreder, Martin
A1  - Samnick, Samuel
A1  - Kropf, Saskia
A1  - Knop, Stefan
A1  - Buck, Andreas K.
A1  - Einsele, Hermann
A1  - Wester, Hans-Juergen
A1  - Kortüm, K. Martin
T1  - CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma
JF  - Theranostics
N2  - C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM).

Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival.

ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive.

CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.
KW  - medicine
KW  - multiple myeloma
KW  - PET
KW  - CXCR4
KW  - theranostics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172095
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Weich, Alexander
A1  - Higuchi, Takahiro
A1  - Schmid, Jan S.
A1  - Schirbel, Andreas
A1  - Lassmann, Michael
A1  - Wild, Vanessa
A1  - Rudelius, Martina
A1  - Kudlich, Theodor
A1  - Herrmann, Ken
A1  - Scheurlen, Michael
A1  - Buck, Andreas K.
A1  - Kropf, Saskia
A1  - Wester, Hans-Jürgen
A1  - Lapa, Constantin
T1  - Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
JF  - Theranostics
N2  - C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
KW  - SSTR
KW  - peptide receptor radionuclide therapy
KW  - neuroendocrine tumor
KW  - [\(^{68}\)Ga]Pentixafor
KW  - CXCR4
KW  - chemokine receptor
KW  - PET/CT
KW  - DOTATOC
KW  - PRRT
KW  - Positronen-Emissions-Tomografie
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158008
VL  - 7
IS  - 6
ER  -