TY - JOUR
T1 - Molecular Imaging in Precision-Cut Non-Small Cell Lung Cancer Slices
AU - Azari, Feredun
AU - Kennedy, Gregory T.
AU - Chang, Ashley
AU - Low, Philip
AU - Basil, Maria
AU - Planer, Joseph
AU - Katzen, Jeremy
AU - Eruslanov, Evgeniy
AU - Albelda, Steven
AU - Singhal, Sunil
N1 - Funding Information:
Feredun Azari has received support from the Training Grant in Surgical Oncology by the National Institutes of Health (NIH) (grant T32CA251063-01 ), The Society of Thoracic Surgeons Thoracic Surgery Foundation Research Award, and the Stephen CC Cheung Fellowship in Surgical Oncology. Gregory T. Kennedy has received support from the American Philosophical Society and the NIH (grant F32 CA254210-01 ). Sunil Singhal has received support from the NIH (grant P01CA254859). All other authors declare that they have no funding sources to disclose.
Publisher Copyright:
© 2024 The Society of Thoracic Surgeons
PY - 2024/2
Y1 - 2024/2
N2 - BACKGROUND: Small animal models remain invaluable for the preclinical study of emerging molecular imaging agents. However, the data obtained in this setting are generated in genetically homogenous animals that do not mimic human pathophysiology. The purpose of this study was to prospectively validate precision-cut lung slices (PCLSs) obtained from patients with lung cancer as a translational tool for the development of targeted fluorophores.METHODS: The lung tissue was gently inflated with 2% Low-Melt Agarose (Fisher, 16520050) to avoid lung damage and minimize inflation pressure. The slices were then loaded into specialized cylindrical cartridges and inserted into a compressotome, and slices 150 to 350 μm thick were cut. Samples were incubated with fluorophore conjugates for ex vivo validation and immunohistochemical staining for receptor expression.RESULTS: A total of 184 unique 3-dimensional, architecturally preserved normal lung and non-small cell lung cancer samples were obtained between 2020 and 2022. The median nodule size was 1.1 ± 0.21 cm for benign lesions and 2.1 ± 0.19 cm for malignant nodules. A total of 101 of 135 (74.8%) malignant lesions were adenocarcinoma spectrum lung cancers. The median viability was 9.78 ± 1.86 days, and 1 μM of FAPL-S0456 (high-affinity fibroblast activation protein [FAP] targeting ligand linked to the near-infrared fluorophore S0456, On Target Laboratories)-targeted near-infrared fluorochrome localization demonstrated correlative labeling of FAP-positive tumor areas with a correlation coefficient of +0.94 (P < .01). There was no FAP fluorochrome uptake in normal lungs (r = -1; P < .001).CONCLUSIONS: PCLSs comprise a novel human tissue-based translational model that can be used to validate the efficacy of molecular imaging fluorochromes. PCLSs preserve the tumor microenvironment and parenchymal architecture that closely resemble the interactions of the immune and stromal components in humans.
AB - BACKGROUND: Small animal models remain invaluable for the preclinical study of emerging molecular imaging agents. However, the data obtained in this setting are generated in genetically homogenous animals that do not mimic human pathophysiology. The purpose of this study was to prospectively validate precision-cut lung slices (PCLSs) obtained from patients with lung cancer as a translational tool for the development of targeted fluorophores.METHODS: The lung tissue was gently inflated with 2% Low-Melt Agarose (Fisher, 16520050) to avoid lung damage and minimize inflation pressure. The slices were then loaded into specialized cylindrical cartridges and inserted into a compressotome, and slices 150 to 350 μm thick were cut. Samples were incubated with fluorophore conjugates for ex vivo validation and immunohistochemical staining for receptor expression.RESULTS: A total of 184 unique 3-dimensional, architecturally preserved normal lung and non-small cell lung cancer samples were obtained between 2020 and 2022. The median nodule size was 1.1 ± 0.21 cm for benign lesions and 2.1 ± 0.19 cm for malignant nodules. A total of 101 of 135 (74.8%) malignant lesions were adenocarcinoma spectrum lung cancers. The median viability was 9.78 ± 1.86 days, and 1 μM of FAPL-S0456 (high-affinity fibroblast activation protein [FAP] targeting ligand linked to the near-infrared fluorophore S0456, On Target Laboratories)-targeted near-infrared fluorochrome localization demonstrated correlative labeling of FAP-positive tumor areas with a correlation coefficient of +0.94 (P < .01). There was no FAP fluorochrome uptake in normal lungs (r = -1; P < .001).CONCLUSIONS: PCLSs comprise a novel human tissue-based translational model that can be used to validate the efficacy of molecular imaging fluorochromes. PCLSs preserve the tumor microenvironment and parenchymal architecture that closely resemble the interactions of the immune and stromal components in humans.
KW - Animals
KW - Humans
KW - Carcinoma, Non-Small-Cell Lung/pathology
KW - Fluorescent Dyes/metabolism
KW - Lung Neoplasms/pathology
KW - Lung/pathology
KW - Molecular Imaging
KW - Tumor Microenvironment
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U2 - 10.1016/j.athoracsur.2023.07.037
DO - 10.1016/j.athoracsur.2023.07.037
M3 - Article
C2 - 37572959
AN - SCOPUS:85172470995
SN - 0003-4975
VL - 117
SP - 458
EP - 465
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 2
ER -