Theranostics · 2026
Porphyrin-lipid nanotheranostics for multimodal imaging of nodal disease in preclinical oral cancers.
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Valic Michael S, Najjar Esmat, Zheng Mark, Townson Jason L, Chan Harley H L, Tzelnick Sharon, Ruaro Alessandra, El-Sayes Abdullah, Halim Michael, Schimmer Pamela, Zhang Chris J, Ye Tina, Jiang Wenlei, Chen Juan, Irish Jonathan C, Zheng Gang
Аннотация
RATIONALE: Cervical lymph node metastases in oral cancer patients are a frequent occurrence and important prognostic factor. Anatomical and molecular imaging modalities can identify neck metastases with varying sensitivity and specificity but perform poorly in clinically negative neck nodes with microscopic disease. Herein we investigate the use of porphyrin-lipid nanotheranostics (PS) for multimodal detection of neck disease in preclinical models of oral cancer.
METHODS: Xenograft models of tongue cancer were established in nude rats using MOC2 mouse oral squamous cells. PS nanoparticles were radiolabelled with positron-emitting Copper-64 (64Cu-PS) and administered either IT (100 MBq 64Cu, 0.5 mg) or IV (250-500 MBq 64Cu/kg, 0.5-1.0 mg/kg). Uptake in the tumour and cervical lymph nodes was measured with serial PET/MR imaging and at endpoint with in situ fluorescence (FL) imaging. In the IV cohort, 64Cu-PS uptake was compared to 18F-FDG (46 MBq 18F/kg) PET performed prior to nanoparticle injection. After imaging, neck nodes were harvested for pathological staging. Receiver operating characteristics were compared in the IV cohort between 18F-FDG vs 64Cu-PS PET imaging vs FL imaging.
RESULTS: The tongue tumour model yielded micrometastases to 54% of neck nodes by 14 d post-implantation. Following IT injection, sentinel and metastatic lymph nodes were visible with 64Cu-PS PET for 72 h. Following IV injection, 64Cu-PS PET signal in the tumour and neck nodes was clearest at 24 h and significant differences in the pooled SUVs of benign vs metastatic nodes were obtained. On FL imaging, metastatic neck nodes had significantly higher fluorescent signal (S/B) compared to benign nodes. Overall, FL S/Bmean gave the best prediction of nodal disease with 75% SEN, 79% SPC, and 71% NPV. 64Cu-PS PET (SUVmax: 77% SEN, 68% SPC, 68% NPV) performed slightly worse than FL imaging for identifying metastatic nodes but still better compared to 18F-FDG PET (SUVmax: 81% SEN, 43% SPC, 59% NPV). Inflamed nodes were the commonest source of false positives for both 64Cu-PS PET and FL imaging modalities.
CONCLUSIONS: Nanotheranostic 64Cu-PS permitted more accurate multimodal detection of microscopic neck disease in preclinical oral cancer models and can offer valuable guidance for planning and performing neck dissections.
METHODS: Xenograft models of tongue cancer were established in nude rats using MOC2 mouse oral squamous cells. PS nanoparticles were radiolabelled with positron-emitting Copper-64 (64Cu-PS) and administered either IT (100 MBq 64Cu, 0.5 mg) or IV (250-500 MBq 64Cu/kg, 0.5-1.0 mg/kg). Uptake in the tumour and cervical lymph nodes was measured with serial PET/MR imaging and at endpoint with in situ fluorescence (FL) imaging. In the IV cohort, 64Cu-PS uptake was compared to 18F-FDG (46 MBq 18F/kg) PET performed prior to nanoparticle injection. After imaging, neck nodes were harvested for pathological staging. Receiver operating characteristics were compared in the IV cohort between 18F-FDG vs 64Cu-PS PET imaging vs FL imaging.
RESULTS: The tongue tumour model yielded micrometastases to 54% of neck nodes by 14 d post-implantation. Following IT injection, sentinel and metastatic lymph nodes were visible with 64Cu-PS PET for 72 h. Following IV injection, 64Cu-PS PET signal in the tumour and neck nodes was clearest at 24 h and significant differences in the pooled SUVs of benign vs metastatic nodes were obtained. On FL imaging, metastatic neck nodes had significantly higher fluorescent signal (S/B) compared to benign nodes. Overall, FL S/Bmean gave the best prediction of nodal disease with 75% SEN, 79% SPC, and 71% NPV. 64Cu-PS PET (SUVmax: 77% SEN, 68% SPC, 68% NPV) performed slightly worse than FL imaging for identifying metastatic nodes but still better compared to 18F-FDG PET (SUVmax: 81% SEN, 43% SPC, 59% NPV). Inflamed nodes were the commonest source of false positives for both 64Cu-PS PET and FL imaging modalities.
CONCLUSIONS: Nanotheranostic 64Cu-PS permitted more accurate multimodal detection of microscopic neck disease in preclinical oral cancer models and can offer valuable guidance for planning and performing neck dissections.