TY - JOUR
T1 - Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression and [64Cu]Cu-DOTA-AE105 uPAR-PET/CT in Patient-Derived Xenograft Models of Oral Squamous Cell Carcinoma
AU - Lawaetz, Mads
AU - Binderup, Tina
AU - Christensen, Anders
AU - Juhl, Karina
AU - Lelkaitis, Giedrius
AU - Lykke, Eva
AU - Knudsen, Line
AU - von Buchwald, Christian
AU - Kjaer, Andreas
N1 - © 2023. The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - PURPOSE: [64Cu]Cu-DOTA-AE105 urokinase-type plasminogen activator receptor (uPAR)-PET/CT is a novel and promising imaging modality for cancer visualization, although it has not been tested in head and neck cancer patients nor in preclinical models that closely resemble these heterogenous tumors, i.e., patient-derived xenograft (PDX) models. The aim of the present study was to establish and validate oral squamous cell carcinoma (OSCC) PDX models and to evaluate [64Cu]Cu-uPAR-PET/CT for tumor imaging in these models.PROCEDURES: PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [64Cu]Cu-DOTA-AE105 was injected in passage 2 (P2) mice, and [64Cu]Cu-uPAR-PET/CT was performed 1 h and 24 h after injection. After the last PET scan, all animals were euthanized, and tumors dissected for autoradiography and immunohistochemical (IHC) staining.RESULTS: Three PDX models were established, and all of them showed histological stability and unchanged heterogenicity, uPAR expression, and Ki67 expression through passages. A significant correlation between uPAR expression and tumor growth was found. All tumors of all models (n=29) showed tumor uptake of [64Cu]Cu-DOTA-AE105. There was a clear visual concordance between the distribution of uPAR expression (IHC) and [64Cu]Cu-DOTA-AE105 uptake pattern in tumor tissue (autoradiography). No significant correlation was found between IHC (H-score) and PET-signal (SUVmax) (r=0.34; p=0.07).CONCLUSIONS: OSCC PDX models in early passages histologically mimic donor tumors and could serve as a valuable platform for the development of uPAR-targeted imaging and therapeutic modalities. Furthermore, [64Cu]Cu-uPAR-PET/CT showed target- and tumor-specific uptake in OSCC PDX models demonstrating the diagnostic potential of this modality for OSCC patients.
AB - PURPOSE: [64Cu]Cu-DOTA-AE105 urokinase-type plasminogen activator receptor (uPAR)-PET/CT is a novel and promising imaging modality for cancer visualization, although it has not been tested in head and neck cancer patients nor in preclinical models that closely resemble these heterogenous tumors, i.e., patient-derived xenograft (PDX) models. The aim of the present study was to establish and validate oral squamous cell carcinoma (OSCC) PDX models and to evaluate [64Cu]Cu-uPAR-PET/CT for tumor imaging in these models.PROCEDURES: PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [64Cu]Cu-DOTA-AE105 was injected in passage 2 (P2) mice, and [64Cu]Cu-uPAR-PET/CT was performed 1 h and 24 h after injection. After the last PET scan, all animals were euthanized, and tumors dissected for autoradiography and immunohistochemical (IHC) staining.RESULTS: Three PDX models were established, and all of them showed histological stability and unchanged heterogenicity, uPAR expression, and Ki67 expression through passages. A significant correlation between uPAR expression and tumor growth was found. All tumors of all models (n=29) showed tumor uptake of [64Cu]Cu-DOTA-AE105. There was a clear visual concordance between the distribution of uPAR expression (IHC) and [64Cu]Cu-DOTA-AE105 uptake pattern in tumor tissue (autoradiography). No significant correlation was found between IHC (H-score) and PET-signal (SUVmax) (r=0.34; p=0.07).CONCLUSIONS: OSCC PDX models in early passages histologically mimic donor tumors and could serve as a valuable platform for the development of uPAR-targeted imaging and therapeutic modalities. Furthermore, [64Cu]Cu-uPAR-PET/CT showed target- and tumor-specific uptake in OSCC PDX models demonstrating the diagnostic potential of this modality for OSCC patients.
KW - Animals
KW - Carcinoma, Squamous Cell/diagnostic imaging
KW - Copper Radioisotopes
KW - Head and Neck Neoplasms
KW - Heterografts
KW - Humans
KW - Mice
KW - Mouth Neoplasms/diagnostic imaging
KW - Positron Emission Tomography Computed Tomography
KW - Receptors, Urokinase Plasminogen Activator/metabolism
KW - Squamous Cell Carcinoma of Head and Neck/diagnostic imaging
KW - Urokinase-type plasminogen activator receptor
KW - Oral squamous cell carcinoma
KW - PET/CT
KW - Cu-DOTA-AE105
KW - Patient-derived xenograft models
UR - http://www.scopus.com/inward/record.url?scp=85172300152&partnerID=8YFLogxK
U2 - 10.1007/s11307-023-01858-x
DO - 10.1007/s11307-023-01858-x
M3 - Journal article
C2 - 37749438
SN - 1536-1632
VL - 25
SP - 1034
EP - 1044
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -