CXCR4-directed imaging in solid tumors

Rudolf A. Werner, Stefan Kircher, Takahiro Higuchi, Malte Kircher, Andreas Schirbel, Hans Jürgen Wester, Andreas K. Buck, Martin G. Pomper, Steven P. Rowe, Constantin Lapa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number770
JournalFrontiers in Oncology
Volume9
Issue numberAUG
DOIs
Publication statusPublished - Jan 1 2019

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Neoplasms
Cholangiocarcinoma
Prostatic Neoplasms
Immunohistochemistry
Neoplasm Metastasis
Neuroendocrine Tumors
Hematologic Diseases
Renal Cell Carcinoma
Ovarian Neoplasms
Hepatocellular Carcinoma
Adenocarcinoma
Liver
Therapeutics

Keywords

  • Chemokine receptor
  • CXCR4
  • Solid tumors
  • Theranostics
  • [Ga]Pentixafor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Werner, R. A., Kircher, S., Higuchi, T., Kircher, M., Schirbel, A., Wester, H. J., ... Lapa, C. (2019). CXCR4-directed imaging in solid tumors. Frontiers in Oncology, 9(AUG), [770]. https://doi.org/10.3389/fonc.2019.00770

CXCR4-directed imaging in solid tumors. / Werner, Rudolf A.; Kircher, Stefan; Higuchi, Takahiro; Kircher, Malte; Schirbel, Andreas; Wester, Hans Jürgen; Buck, Andreas K.; Pomper, Martin G.; Rowe, Steven P.; Lapa, Constantin.

In: Frontiers in Oncology, Vol. 9, No. AUG, 770, 01.01.2019.

Research output: Contribution to journalArticle

Werner, RA, Kircher, S, Higuchi, T, Kircher, M, Schirbel, A, Wester, HJ, Buck, AK, Pomper, MG, Rowe, SP & Lapa, C 2019, 'CXCR4-directed imaging in solid tumors', Frontiers in Oncology, vol. 9, no. AUG, 770. https://doi.org/10.3389/fonc.2019.00770
Werner RA, Kircher S, Higuchi T, Kircher M, Schirbel A, Wester HJ et al. CXCR4-directed imaging in solid tumors. Frontiers in Oncology. 2019 Jan 1;9(AUG). 770. https://doi.org/10.3389/fonc.2019.00770
Werner, Rudolf A. ; Kircher, Stefan ; Higuchi, Takahiro ; Kircher, Malte ; Schirbel, Andreas ; Wester, Hans Jürgen ; Buck, Andreas K. ; Pomper, Martin G. ; Rowe, Steven P. ; Lapa, Constantin. / CXCR4-directed imaging in solid tumors. In: Frontiers in Oncology. 2019 ; Vol. 9, No. AUG.
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abstract = "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-na{\"i}ve 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-na{\"i}ve 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.",
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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

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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.

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KW - Chemokine receptor

KW - CXCR4

KW - Solid tumors

KW - Theranostics

KW - [Ga]Pentixafor

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