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Purpose: One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000–1700 nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa. This study aims to construct a new NIR-II probe targeting B7-H3 (AbB7−H3-800CW) for accurate intraoperative identification and resection of PCa. Methods: Based on the differential expression of B7-H3 in PCa, we designed a novel imaging probe to accurately identify and guide the resection of preclinical PCa models and ex vivo human PCa tissues using NIR-II fluorescence imaging technology. Results: Analyzing tissue samples from 60 clinical cases of PCa, along with benign prostatic hyperplasia and normal prostate tissue from 22 cases, we observed a significant difference in B7-H3 protein expression levels (P < 0.001). Subcutaneous and orthotopic mouse models of PCa were imaged using NIR-II fluorescence after AbB7−H3-800CW injection, showing promising results with successful tumor targeting and high-contrast images achieved within 24–48 h post-injection. The imaging also enabled the detection of occult PCa lesions approximately 1 mm in diameter. In addition, imaging analysis of human PCa and adjacent tissues using AbB7−H3-800CW incubation revealed that cancer tissues exhibited a significantly higher fluorescence intensity than adjacent tissues (P < 0.05), which was conducive to the evaluation of tumor resection margin in vitro. Conclusion: The findings revealed that B7-H3 was a compelling imaging target for PCa. The AbB7−H3-800CW molecular imaging probe is capable of accurately identifying PCa lesions and guiding their removal. This approach can potentially reduce the rate of surgical margins under NIR-II fluorescence guidance. [ABSTRACT FROM AUTHOR]

Purpose: During lung cancer surgery, it is very important to define tumor boundaries and determine the surgical margin distance. In previous research, systemically application of fluorescent probes can help medical professionals determine the boundaries of tumors and find small tumors and metastases, thereby improving the accuracy of surgical resection. However, there are very few safe and effective probes that can be applied to clinical trials up to now, which limits the clinical application of fluorescence imaging. Here we developed a new technology that can quickly identify the tumor area in the resected lung tissue during the operation and distinguish the tumor boundary and metastatic lymph nodes. Experimental design: For animal studies, a PDX model of lung cancer was established. The tumors, lungs, and peritumoral muscle tissues of tumor-bearing mice were surgically removed and incubated with a probe targeting epidermal growth factor receptor (EGFR) for 20 min, and then imaged by a closed-field near-infrared two-zone (NIR-II) fluorescence imaging system. For clinical samples, ten surgically removed lung tissues and 60 lymph nodes from 10 lung cancer patients undergoing radical resection were incubated with the targeting probe immediately after intraoperative resection and imaged to identify the tumor area and distinguish the tumor boundary and metastatic lymph nodes. The accuracy of fluorescence imaging was confirmed by HE staining and immunohistochemistry. Results: The ex vivo animal imaging experiments showed a fluorescence enhancement of tumor tissue. For clinical samples, our results showed that this new technology yielded more than 85.7% sensitivity and 100% specificity in identifying the tumor area in the resected lung tissue. The average fluorescence tumor-to-background ratio was 2.5 ± 1.3. Furthermore, we also used this technique to image metastatic lymph nodes intraoperatively and showed that metastatic lymph nodes have brighter fluorescence than normal lymph nodes, as the average fluorescence tumor-to-background signal ratio was 2.7 ± 1.1. Calculations on the results of the fluorescence signal in relation to the number of metastatic lymph nodes yielded values of 77.8% for sensitivity and 92.1% for specificity. We expect this new technology to be a useful diagnostic tool for rapid intraoperative pathological detection and margin determination. Conclusions: By using fluorescently labeled anti-human EGFR recombinant antibody scFv fragment to incubate freshly isolated tissues during surgery, the probes can quickly accumulate in lung cancer tissues, which can be used to quickly identify tumor areas in the resected lung tissues and distinguish tumor boundaries and find metastases in lymph nodes. This technology is expected to be used for rapid intraoperative pathological detection and margin determination. [ABSTRACT FROM AUTHOR]

Purpose: The surgery of glioblastoma (GBM) requires a maximal resection of the tumor when it is safe and feasible. The infiltrating growth property of the GBM makes it a challenge for neurosurgeons to identify the tumor tissue even with the assistance of the surgical microscope. This highlights the urgent requirement for imaging techniques that can differentiate tumor tissues during surgery in real time. Fluorescence image-guided surgery of GBM has been investigated using several non-specific fluorescent probes that emit light in the visible and the first near-infrared window (NIR-I, 700–900 nm), which limit the detection accuracy because of the non-specific targeting mechanism and spectral characteristics. Targeted NIR-II (1000–1700 nm) fluorescent probes for GBM are thus highly desired. The folate receptor (FR) has been reported to be upregulated in GBM, which renders it to be a promising target for specific tumor imaging. Methods: In this study, the folic acid (FA) that can target the FR was conjugated with the clinically approved indocyanine green (ICG) dye and DOTA chelator for radiolabeling with 64Cu to achieve targeted positron emission tomography (PET) and fluorescence imaging of GBM. Results: Surprisingly it was found that the resulted bioconjugate, DOTA-FA-ICG and non-radioactive natCu-DOTA-FA-ICG, were both self-assembled into nanoparticles with NIR-II emission signal. The radiolabeled DOTA-FA-ICG, 64Cu-DOTA-FA-ICG, was found to specifically accumulate in the orthotopic GBM models using in vivo PET, NIR-II, and NIR-I fluorescence imaging. The best time window of fluorescence imaging was demonstrated to be 24 h after DOTA-FA-ICG injection. NIR-II fluorescence image-guided surgery was successfully conducted in the orthotopic GBM models using DOTA-FA-ICG. All the fluorescent tissue was removed and proved to be GBM by the H&E examination. Conclusion: Overall, our study demonstrates that the probes, 64Cu-DOTA-FA-ICG and DOTA-FA-ICG, hold promise for preoperative PET examination and intraoperative NIR-II fluorescence image-guided surgery of GBM, respectively. [ABSTRACT FROM AUTHOR]

Purpose: China has the largest cancer population globally. Surgery is the main choice for most solid cancer patients. Intraoperative fluorescence molecular imaging (FMI) has shown its great potential in assisting surgeons in achieving precise resection. We summarized the typical applications of intraoperative FMI and several new trends to promote the development of precision surgery. Methods: The academic database and NIH clinical trial platform were systematically evaluated. We focused on the clinical application of intraoperative FMI in China. Special emphasis was placed on a series of typical studies with new technologies or high-level evidence. The emerging strategy of combining FMI with other modalities was also discussed. Results: The clinical applications of clinically approved indocyanine green (ICG), methylene blue (MB), or fluorescein are on the rise in different surgical departments. Intraoperative FMI has achieved precise lesion detection, sentinel lymph node mapping, and lymphangiography for many cancers. Nerve imaging is also exploring to reduce iatrogenic injuries. Through different administration routes, these fluorescent imaging agents provided encouraging results in surgical navigation. Meanwhile, designing new cancer-specific fluorescent tracers is expected to be a promising trend to further improve the surgical outcome. Conclusions: Intraoperative FMI is in a rapid development in China. In-depth understanding of cancer-related molecular mechanisms is necessary to achieve precision surgery. Molecular-targeted fluorescent agents and multi-modal imaging techniques might play crucial roles in the era of precision surgery. [ABSTRACT FROM AUTHOR]

The article presents a case study of 51-year-old woman, diagnosed with cervical cancer, consented to being included in a clinical trial (NCT05087264). The patient underwent a radical hysterectomy with pelvic lymphadenectomy. Preoperatively, indocyanine green ([ICG], 5 mg/kg) was intravenously injected for 24 h, and it emitted a tail fluorescence in the NIR-II spectrum.

Purpose: Surgery is the predominant treatment modality of human glioma but suffers difficulty on clearly identifying tumor boundaries in clinic. Conventional practice involves neurosurgeon's visual evaluation and intraoperative histological examination of dissected tissues using frozen section, which is time-consuming and complex. The aim of this study was to develop fluorescent imaging coupled with artificial intelligence technique to quickly and accurately determine glioma in real-time during surgery. Methods: Glioma patients (N = 23) were enrolled and injected with indocyanine green for fluorescence image–guided surgery. Tissue samples (N = 1874) were harvested from surgery of these patients, and the second near-infrared window (NIR-II, 1000–1700 nm) fluorescence images were obtained. Deep convolutional neural networks (CNNs) combined with NIR-II fluorescence imaging (named as FL-CNN) were explored to automatically provide pathological diagnosis of glioma in situ in real-time during patient surgery. The pathological examination results were used as the gold standard. Results: The developed FL-CNN achieved the area under the curve (AUC) of 0.945. Comparing to neurosurgeons' judgment, with the same level of specificity >80%, FL-CNN achieved a much higher sensitivity (93.8% versus 82.0%, P < 0.001) with zero time overhead. Further experiments demonstrated that FL-CNN corrected >70% of the errors made by neurosurgeons. FL-CNN was also able to rapidly predict grade and Ki-67 level (AUC 0.810 and 0.625) of tumor specimens intraoperatively. Conclusion: Our study demonstrates that deep CNNs are better at capturing important information from fluorescence images than surgeons' evaluation during patient surgery. FL-CNN is highly promising to provide pathological diagnosis intraoperatively and assist neurosurgeons to obtain maximum resection safely. Trial registration: ChiCTR ChiCTR2000029402. Registered 29 January 2020, retrospectively registered [ABSTRACT FROM AUTHOR]