Department of Nuclear Medicine, Medical School, University of Pécs, Pécs, Hungary.
Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary.
Sci Rep. 2021 Dec 14;11(1):24002. doi: 10.1038/s41598-021-03505-3.
Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[F]fluoro-D-glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with F-Fluorine (F-18) and Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of Ga. CLI with Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.
切伦科夫发光成像（CLI）是一种很有前途的方法，可用于图像引导手术和病理采样。当与全身同位素断层扫描相结合时，它可能会提供额外的优势。我们旨在获得其在淋巴瘤病理诊断中应用的证据，因此我们决定研究新型自发高级 B 细胞淋巴瘤小鼠模型（Bc.DLFL1）中 PET 或 SPECT/CLI 联合的放射诊断潜力。我们在早期、晚期和终末期等临床相关阶段通过体内 2-脱氧-2-[F]氟-D-葡萄糖（FDG）正电子发射断层扫描（PET）/磁共振成像（MRI）和 Ga-柠檬酸单光子发射计算机断层扫描（SPECT）/MRI 监测淋巴瘤的扩散。体内成像与离体高分辨率 CLI 相结合。因此，测试了 CLI 与 F-氟（F-18）和 Ga-镓同位素在选择浸润淋巴结进行肿瘤分期和病理检查中的应用。在晚期，FDG PET/MRI 加离体 CLI 允许准确检测淋巴瘤浸润组织中的 FDG 积累。在终末期，我们使用 SPECT/MRI 检测到肿瘤性淋巴结，并且可以报告体内 Ga 的切伦科夫光发射的检测。Ga-柠檬酸的 CLI 显示了远处淋巴结位置的淋巴瘤积累，仅凭 MRI 无法检测到。流式细胞术和免疫组织化学证实了这些成像结果。我们的研究促进了 PET 和 CLI 在临床前研究和临床实践中的联合应用。在取样手术中检测到的淋巴结中 FDG 分布不均，对组织病理学处理有影响，并可能指导治疗。Ga 的结果也表明有机会进一步应用合适的 SPECT 放射性药物进行 CLI。
