TY - JOUR
T1 - CXCR4-directed imaging in solid tumors
AU - Werner, Rudolf A.
AU - Kircher, Stefan
AU - Higuchi, Takahiro
AU - Kircher, Malte
AU - Schirbel, Andreas
AU - Wester, Hans Jürgen
AU - Buck, Andreas K.
AU - Pomper, Martin G.
AU - Rowe, Steven P.
AU - Lapa, Constantin
N1 - Funding Information:
This work was supported by the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and German Research Council (DFG grant HI 1789/3-3). This publication was funded by the German Research Foundation (DFG) and the University of Wuerzburg in the funding programme Open Access Publishing. This work was supported by Grants-in-Aid for Scientific Research (Kakenhi, 15K21774) from the Japan Society for the Promotion of Science (JSPS).
Publisher Copyright:
© 2019 Werner, Kircher, Higuchi, Kircher, Schirbel, Wester, Buck, Pomper, Rowe and Lapa.
PY - 2019
Y1 - 2019
N2 - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms. Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [68 Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUVmax) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [68 Ga]Pentixafor findings were further compared to immunohistochemistry and [18 F]FDG PET/CT. Results: On [68 Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [68 Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [68 Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [18 F]FDG PET/CT was available, [68 Ga]Pentixafor exhibited lower uptake in all lesions. Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [68 Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.
AB - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms. Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [68 Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUVmax) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [68 Ga]Pentixafor findings were further compared to immunohistochemistry and [18 F]FDG PET/CT. Results: On [68 Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [68 Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [68 Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [18 F]FDG PET/CT was available, [68 Ga]Pentixafor exhibited lower uptake in all lesions. Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [68 Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.
KW - CXCR4
KW - Chemokine receptor
KW - Solid tumors
KW - Theranostics
KW - [Ga]Pentixafor
UR - http://www.scopus.com/inward/record.url?scp=85071695986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071695986&partnerID=8YFLogxK
U2 - 10.3389/fonc.2019.00770
DO - 10.3389/fonc.2019.00770
M3 - Article
C2 - 31475113
AN - SCOPUS:85071695986
SN - 2234-943X
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
IS - AUG
M1 - 770
ER -