The value of terahertz three-dimensional tomography for the differential diagnosis of tumor tissue and normal tissue in lung cancer nude mice

Introduction To investigate the value of terahertz (THz) spectroscopy combined with gold nanorods (GNRs) in the differential diagnosis of lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Methods Tumor-bearing nude mouse models were established using GNR-treated A549 (LUAD) and NCI-H520 (LUSC) cells. Reflective THz 3D imaging and transmission THz time-domain spectroscopy (THz-TDS) systems, together with CT imaging and pathological validation, were employed to analyze the THz spectral characteristics of in vivo tumors, paraffin-embedded tissues, and thin sections. Results CCK-8 and live/dead staining supported the biocompatibility of 40 μg/mL GNRs under the tested conditions. In vivo THz imaging showed higher tumor-region signals in the GNR-treated groups. At 0.5 THz, the model-specific tumor-to-adjacent skin/subcutaneous ROI contrast ratio in the LUSC group was 36:1 after GNR treatment and 22:1 in the untreated control; The contrast ratio of the GNR-treated LUSC group is 25:1, while that of the untreated control group is 19:1. Among the tested frequency bands, 0.5 THz provided the clearest image contrast. Contrast decreased markedly in paraffin-embedded tissues (approximately 2:1), and spectral differences in routine 5 μm human sections were obscured by the glass substrate. These findings support proof-of-concept signal enhancement in a subcutaneous xenograft model but do not establish a clinical tumor-to-normal-lung contrast ratio. Discussion Under the tested conditions, GNR treatment was associated with higher THz signals in subcutaneous LUSC and LUAD xenografts. The mechanism and clinical performance remain unestablished; the approach should be regarded as proof-of-concept and as a potential complement to, rather than a replacement for, standard histopathology.