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CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors—a comprehensive analysis of imaging findings and comparison with histopathology

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Názov: CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors—a comprehensive analysis of imaging findings and comparison with histopathology
Autori: Niklas Dreher, Stefanie Hahner, Carmina T. Fuß, Wiebke Schlötelburg, Philipp E. Hartrampf, Sebastian E. Serfling, Andreas Schirbel, Samuel Samnick, Takahiro Higuchi, Alexander Weich, Constantin Lapa, Andreas Rosenwald, Andreas K. Buck, Stefan Kircher, Rudolf A. Werner
Zdroj: Eur J Nucl Med Mol Imaging
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2023.
Rok vydania: 2023
Predmety: ddc:610, 03 medical and health sciences, Receptors, CXCR4, 0302 clinical medicine, Coordination Complexes, Positron Emission Tomography Computed Tomography, Neoplasms, Humans, Original Article, Gallium Radioisotopes, PET/CT, Humans [MeSH], Radioligand therapy, Theranostics, Peptides, Cyclic [MeSH], Solid tumors, Neoplasms/diagnostic imaging [MeSH], Gallium Radioisotopes [MeSH], C-X-C motif chemokine receptor 4, Positron Emission Tomography Computed Tomography/methods [MeSH], [, CXCR4, Receptors, CXCR4/metabolism [MeSH], Coordination Complexes [MeSH], Peptides, Cyclic, 3. Good health
Popis: Background C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings. Methods A total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients’ tumor tissue and investigated possible correlations with SUVmax (by providing Spearman’s rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10). Results One hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05–24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort. Conclusions In a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.
Druh dokumentu: Article
Other literature type
Popis súboru: application/pdf
Jazyk: English
ISSN: 1619-7089
1619-7070
DOI: 10.1007/s00259-023-06547-z
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38082196
https://repository.publisso.de/resource/frl:6508689
https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-382254
https://doi.org/10.1007/s00259-023-06547-z
https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/38225
https://opus.bibliothek.uni-wuerzburg.de/files/38225/s00259-023-06547-z.pdf
Rights: CC BY
Prístupové číslo: edsair.doi.dedup.....30934287e96d88d184999a57e48ac28f
Databáza: OpenAIRE
Popis
Abstrakt:Background C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings. Methods A total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients’ tumor tissue and investigated possible correlations with SUVmax (by providing Spearman’s rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10). Results One hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05–24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort. Conclusions In a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.
ISSN:16197089
16197070
DOI:10.1007/s00259-023-06547-z