Molecular imaging of pathologic lesions can improve efficient detection of cancer and cardiovascular diseases. A shared pathophysiological feature is angiogenesis, the formation of new blood vessels. Endoglin (CD105) is a coreceptor for ligands of the Transforming Growth Factor-β (TGF-β) family and is highly expressed on angiogenic endothelial cells. Therefore, endoglin-based imaging has been explored to visualize lesions of the aforementioned diseases. This systematic review highlights the progress in endoglin-based imaging of cancer, atherosclerosis, myocardial infarction, and aortic aneurysm, focusing on positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), near-infrared fluorescence (NIRF) imaging, and ultrasound imaging. PubMed was searched combining the following subjects and their respective synonyms or relevant subterms: “Endoglin”, “Imaging/Image-guided surgery”. In total, 59 papers were found eligible to be included: 58 reporting about preclinical animal or in vitro models and one ex vivo study in human organs. In addition to exact data extraction of imaging modality type, tumor or cardiovascular disease model, and tracer (class), outcomes were described via a narrative synthesis. Collectively, the data identify endoglin as a suitable target for intraoperative and diagnostic imaging of the neovasculature in tumors, whereas for cardiovascular diseases, the evidence remains scarce but promising.

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

Background: The use of fluorescence agents and imaging systems is a promising adjunct in the surgical management of colorectal cancer. This systematic review and meta-analysis aimed to assess the safety and efficacy of fluorescence-guided surgery in the management of colorectal cancer, with a comparison to conventional (non-fluorescence-guided) surgery. Methods: A literature search of MEDLINE, Embase, Emcare, and CINAHL databases was performed for studies that reported data on the outcomes of fluorescence-guided surgery, with or without a comparison group undergoing conventional surgery, for colorectal cancer between January 2000 and January 2024. A meta-analysis was performed using random-effect models, and between-study heterogeneity was assessed. Results: 35 studies of 3217 patients with colorectal cancer were included: 26 studies (964 patients) reported on fluorescence-guided surgery and 9 studies (2253 patients) reported on fluorescence versus conventional surgery. The weighted mean of the cancer detection rate of fluorescence-guided surgery was 71% (95% CI 0.55–0.85), with no significant difference in lymph node yield ratio (WMD −0.04; 95% CI −0.10–0.02; p = 0.201) between fluorescence and conventional surgery groups. There was a significantly lower blood loss (WMD −4.38; 95% CI −7.05–−1.70; p = 0.001) and complication rate (WMD −0.04; 95% CI −0.07–0.00; p = 0.027) in the fluorescence-guided surgery group, with a potentially lower anastomotic leak rate (WMD −0.05; 95% CI −0.10–0.01; p = 0.092). Conclusions: Fluorescence-guided surgery is a safe and effective approach in the management of colorectal cancer, potentially reducing blood loss and complications. Further randomised controlled trials are required comparing fluorescence-guided surgery with conventional surgery to determine its prognostic benefit and where it should precisely fit within the management pathway of colorectal cancer.

Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence tumor imaging by endoscopy to differentiate responders and the effect of nCRT on their expression. Methods: RC samples (n = 51) were collected from both pre-treatment biopsies and corresponding post-treatment surgical specimens. Samples were categorized by treatment response and determined using tumor regression grade (TRG) scoring. Immunohistochemistry assessed the expression of CEA, EpCAM, EGFR, and c-MET in tumors and adjacent normal tissues. Expression levels were quantified using H-scores (0–3), combining the percentage and intensity of stained cells. Pre- and post-treatment H-scores were compared to evaluate the impact of nCRT. Results: CEA, EpCAM, and c-MET were overexpressed in tumor tissue as compared to adjacent healthy mucosa in 100% (51/51), 98.4% (50/51), and 92% (47/51) of tumor biopsies, respectively, while EGFR showed no overexpression. A tumor-to-normal (T/N) ratio ≥ 2 was considered sufficient for differentiation in molecular fluorescence imaging. In pre-treatment biopsy samples, c-MET showed the highest T/N expression ratio (53% of the samples ≥ 2), followed by CEA (26.3%) and EpCAM (16%). Following nCRT treatment, CEA and c-MET maintained a ≥ 2 differential expression in 45% of all samples, whereas EpCAM exhibited this difference in only 9.2% of cases. Neoadjuvant therapy even significantly improved the T/N expression ratio for CEA and c-MET (p < 0.01) and EpCAM (p < 0.05), while EGFR expression remained lower than adjacent normal tissue. Significant increases in all marker expressions were observed in minimal responders (TRG4/5, p < 0.01–0.001), while near-complete responders (TRG2) exhibited non-significant changes in CEA, c-MET, and EGFR expression. Conclusions: c-MET and CEA emerged as optimal tumor imaging targets, showing sustained differential expression after nCRT. In vivo fluorescence-guided endoscopy using probes against these markers could play a role in future clinical decision-making.