Abstract
Combining near-infrared fluorescence (NIRF) and nuclear imaging techniques provides a novel approach for hepatocellular carcinoma (HCC) diagnosis. Here, we report the synthesis and characteristics of a dual-modality NIRF optical/positron emission tomography (PET) imaging probe using heptamethine carbocyanine dye and verify its feasibility in both nude mice and rabbits with orthotopic xenograft liver cancer. This dye, MHI-148, is an effective cancer-specific NIRF imaging agent and shows preferential uptake and retention in liver cancer. The corresponding NIRF imaging intensity reaches 109/cm2 tumor area at 24 h after injection in mice with HCC subcutaneous tumors. The dye can be further conjugated with radionuclide 68Ga (68Ga-MHI-148) for PET tracing. We applied the dual-modality methodology toward the detection of HCC in both patient-derived orthotopic xenograft (PDX) models and rabbit orthotopic transplantation models. NIRF/PET images showed clear tumor delineation after probe injection (MHI-148 and 68Ga-MHI-148). The tumor-to-muscle (T/M) standardized uptake value (SUV) ratios were obtained from PET at 1 h after injection of 68Ga-MHI-148, which was helpful for effectively capturing small tumors in mice (0.5 cm × 0.3 cm) and rabbits (1.2 cm × 1.8 cm). This cancer-targeting NIRF/PET dual-modality imaging probe provides a proof of principle for noninvasive detection of deep-tissue tumors in mouse and rabbit and is a promising technique for more accurate and early detection of HCC.
Highlights
Diverse imaging modalities have been used for liver cancer diagnosis, including positron emission tomographycomputed tomography (PET/CT) [1], magnetic resonance imaging (MRI) [2], and fluorescence molecular imaging (FMI) [3]
Mice bearing xenograft tumors were injected intraperitoneally with MHI148, and higher intensity Near-infrared fluorescent (NIRF) signals were detected at tumor sites compared to those detected with marginal light using whole-body NIRF imaging (Figure 2(a))
We observed identical histologies in PDXderived tumor tissues and the original patients’ tumor samples using hematoxylin and eosin (H&E) staining, which was accompanied by the strong expression of AFP, a marker highly expressed in hepatocellular carcinoma (HCC) (Figures 2(c) and 2(d))
Summary
Diverse imaging modalities have been used for liver cancer diagnosis, including positron emission tomographycomputed tomography (PET/CT) [1], magnetic resonance imaging (MRI) [2], and fluorescence molecular imaging (FMI) [3]. PET for nuclear imaging has distinct advantages in the detection of tumors, possessing high tissue penetration and noninvasive properties capable of monitoring the metabolic and molecular characteristics of cancer cells [5]. These probes often exhibit shortcomings, such as a short half-life, low spatial resolution, exposure to radiation, and abundant uptake by tissues with high basal metabolic rates, such as the brain [6].
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