Molecular Imaging in Precision-Cut Non-Small Cell Lung Cancer Slices.
Ann Thorac Surg
; 117(2): 458-465, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-37572959
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article