En Bloc Tumor Resection, Optical Molecular Imaging, and the Potential Synergy of the Combination of the Two Techniques in Bladder Cancer

Although transurethral resection of bladder tumor is the golden standard for the treatment of non-muscle invasive bladder cancer, this surgical procedure still has some serious drawbacks. For example, piecemeal resection of tumor tissue results in exfoliated tumor cells dissemination and implantation, and fragmented tumor specimens make it difficult for pathologists to accurately assess the pathological stage and histologic grade. En bloc tumor resection follows the basic principle of oncological surgery and provides an intact tumor specimen containing detrusor muscle for pathologists to make accurate histopathological assessment. However, there is no robust clinical evidence that en bloc tumor resection is superior to conventional resection in terms of oncological outcomes. Considering the high recurrence rate, small or occult tumor lesions may be overlooked and incomplete tumor resection may occur during white light cystoscopy-assisted transurethral resection. Molecular fluorescent tracers have the ability to bind tumor cells with high sensitivity and specificity. Optical molecular imaging mediated by it can detect small or occult malignant lesions while minimizing the occurrence of false-positive results. Meanwhile, optical molecular imaging can provide dynamic and real-time image guidance in the surgical procedure, which helps urologists to accurately determine the boundary and depth of tumor invasion, so as to perform complete and high-quality transurethral tumor resection. Integrating the advantages of these two technologies, optical molecular imaging-assisted en bloc tumor resection shows the potential to improve the positive detection rate of small or occult tumor lesions and the quality of transurethral resection, resulting in high recurrence-free and progression-free survival rates.

Shortwave infrared emitting multicolored nanoprobes for biomarker-specific cancer imaging in vivo

Background The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900–1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. Methods SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. Results Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. Conclusions The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.