CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather
Purpose CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [ 68 Ga]Ga-Pentixafor and i...
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Published in | European journal of nuclear medicine and molecular imaging Vol. 49; no. 2; pp. 481 - 491 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.01.2022
Springer Nature B.V |
Subjects | |
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Abstract | Purpose
CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [
68
Ga]Ga-Pentixafor and its therapeutic counterpart [
177
Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents.
Methods
CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and
MGMT
promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [
68
Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4.
Results
Two large mRNA datasets (
N
= 284;
N
= 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients—not directly translatable to [
68
Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or
MGMT
status or survival.
Conclusion
Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [
68
Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [
177
Lu]Lu-Pentixather in the future. |
---|---|
AbstractList | Purpose
CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [
68
Ga]Ga-Pentixafor and its therapeutic counterpart [
177
Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents.
Methods
CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and
MGMT
promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [
68
Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4.
Results
Two large mRNA datasets (
N
= 284;
N
= 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients—not directly translatable to [
68
Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or
MGMT
status or survival.
Conclusion
Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [
68
Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [
177
Lu]Lu-Pentixather in the future. PurposeCXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [68Ga]Ga-Pentixafor and its therapeutic counterpart [177Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents.MethodsCXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [68Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4.ResultsTwo large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients—not directly translatable to [68Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival.ConclusionUsing immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [68Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [177Lu]Lu-Pentixather in the future. CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [ Ga]Ga-Pentixafor and its therapeutic counterpart [ Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents. CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [ Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4. Two large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients-not directly translatable to [ Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival. Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [ Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [ Lu]Lu-Pentixather in the future. Abstract Purpose CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [ 68 Ga]Ga-Pentixafor and its therapeutic counterpart [ 177 Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents. Methods CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [ 68 Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4. Results Two large mRNA datasets ( N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients—not directly translatable to [ 68 Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival. Conclusion Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [ 68 Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [ 177 Lu]Lu-Pentixather in the future. |
Author | Wesseling, Pieter de Keizer, Bart Ververs, F. F. Tessa Tolboom, Nelleke Jacobs, Sarah M. Krijger, Gerard C. van der Kolk, Anja G. Snijders, Tom J. Westerman, Bart A. Robe, Pierre A. |
Author_xml | – sequence: 1 givenname: Sarah M. orcidid: 0000-0003-0147-9511 surname: Jacobs fullname: Jacobs, Sarah M. email: s.m.jacobs@umcutrecht.nl organization: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht – sequence: 2 givenname: Pieter orcidid: 0000-0001-5453-5201 surname: Wesseling fullname: Wesseling, Pieter organization: Princess Máxima Center for Pediatric Oncology, Department of Pathology, Amsterdam University Medical Centers/VUmc – sequence: 3 givenname: Bart orcidid: 0000-0002-6270-9483 surname: de Keizer fullname: de Keizer, Bart organization: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht – sequence: 4 givenname: Nelleke orcidid: 0000-0002-8005-2833 surname: Tolboom fullname: Tolboom, Nelleke organization: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht – sequence: 5 givenname: F. F. Tessa surname: Ververs fullname: Ververs, F. F. Tessa organization: Department of Clinical Pharmacy, University Medical Center Utrecht – sequence: 6 givenname: Gerard C. surname: Krijger fullname: Krijger, Gerard C. organization: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht – sequence: 7 givenname: Bart A. orcidid: 0000-0002-9898-9616 surname: Westerman fullname: Westerman, Bart A. organization: Department of Pathology, Amsterdam University Medical Centers/VUmc – sequence: 8 givenname: Tom J. orcidid: 0000-0003-0857-081X surname: Snijders fullname: Snijders, Tom J. organization: UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht – sequence: 9 givenname: Pierre A. surname: Robe fullname: Robe, Pierre A. organization: UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht – sequence: 10 givenname: Anja G. orcidid: 0000-0002-8267-8848 surname: van der Kolk fullname: van der Kolk, Anja G. organization: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Department of Radiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital |
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Keywords | Molecular imaging Ga]Ga-Pentixafor Glioblastoma CXCR4 [ Lu]Lu-Pentixather PET [68Ga]Ga-Pentixafor [177Lu]Lu-Pentixather |
Language | English |
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PublicationTitle | European journal of nuclear medicine and molecular imaging |
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CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated... CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a... Abstract Purpose CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is... PurposeCXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated... PURPOSECXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated... |
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SubjectTerms | Blood vessels Brain cancer Cardiology Coordination Complexes CXCR4 protein Cytoplasm DNA methylation Gallium Radioisotopes Gene expression Glioblastoma Glioblastoma - diagnostic imaging Glioblastoma - genetics Glioblastoma - therapy Humans Imaging Immunohistochemistry Lutetium isotopes Medical prognosis Medicine Medicine & Public Health Neoplasm Recurrence, Local Neuroimaging Nuclear Medicine Oncology Original Original Article Orthopedics Patients Peptides, Cyclic - metabolism Phenotypes Positron emission Positron emission tomography Positron-Emission Tomography - methods Radiation therapy Radioisotopes Radiology Receptors, CXCR4 - genetics Staining Tomography Translational research Tumor cells Tumors |
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Title | CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather |
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