Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

Buckle, Tessa; Alphen, M.J.A. van; Oosterom, Matthias N. van; Beurden, Florian van; Heimburger, Nina; Wal, Jaqueline E. van der; Brekel, Michiel W. M. van den; Leeuwen, Fijs W. B. van; Karakullukçu, Barış

doi:10.3390/cancers13112674

Cited by 8 publications

(21 citation statements)

References 36 publications

(66 reference statements)

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“…2 C, top image). Placement of the Cy5-specific click-on filter [ 27 ] or a filter wheel that facilitated (Fig. 2 B, *) easy switching between white light and Cy5 imaging mode (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2 In vivo imaging of basal PSMA levels in the porcine prostate using clinical imaging equipment. A Imaging setup showing the operating surgeons (on the left) handing the Da Vinci surgical robot (center) and the Cy5-dedicated laparoscopic imaging setup from KARL STORZ (on the right; [ 26 , 27 ]). B ) In-house developed click-on multispectral filter wheel (*) enabling switching between white light imaging and Cy5 imaging.…”

Section: Resultsmentioning

confidence: 99%

“…B ) In-house developed click-on multispectral filter wheel (*) enabling switching between white light imaging and Cy5 imaging. C In vivo visualization of the prostate using white light imaging (top), receptor-mediated PSMA imaging (basal expression) after intravenous administration of EuK‐(SO 3 )Cy5‐mas 3 (center; red on black) and real-time color coding of the fluorescence signal and corresponding signal-to-background ratio (SBR) in the prostate using in-house developed software [ 26 , 27 ] …”

Section: Resultsmentioning

confidence: 99%

“…In-house developed image processing software was used to create color-coded heat-map and real-time representation of the signal-to-background ratio (SBR) based on the intensity of the fluorescence signal [ 27 ]. Differences in fluorescence signal intensity were represented in an intensity-based scale-bar in real time.…”

Section: Methodsmentioning

confidence: 99%

“…Hereafter, samples were formalin-fixed and then paraffin-embedded. Real-time image processing of the fluorescence image was applied to provide a representation of the SBR and fluorescence signal intensity differences within the tissue [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

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Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

et al. 2022

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Background With the rise of prostate-specific membrane antigen (PSMA) radioguided surgery, which is performed using a microdosing regime, demand for visual target confirmation via fluorescence guidance is growing. While proven very effective for radiotracers, microdosing approaches the detection limit for fluorescence imaging. Thus, utility will be highly dependent on the tracer performance, the sensitivity of the fluorescence camera used, and the degree of background signal. Using a porcine model the ability to perform robot-assisted radical prostatectomy under fluorescence guidance using the bimodal or rather hybrid PSMA tracer (99mTc-EuK-(SO3)Cy5-mas3) was studied, while employing the tracer in a microdosing regime. This was followed by ex vivo evaluation in surgical specimens obtained from prostate cancer patients. Results T50% blood and T50% urine were reached at 85 min and 390 min, in, respectively, blood and urine. Surgical fluorescence imaging allowed visualization of the prostate gland based on the basal PSMA-expression in porcine prostate. Together, in vivo visualization of the prostate and urinary excretion suggests at least an interval of > 7 h between tracer administration and surgery. Confocal microscopy of excised tissues confirmed tracer uptake in kidney and prostate, which was confirmed with PSMA IHC. No fluorescence was detected in other excised tissues. Tumor identification based on ex vivo fluorescence imaging of human prostate cancer specimens correlated with PSMA IHC. Conclusion Intraoperative PSMA-mediated fluorescence imaging with a microdosing approach was shown to be feasible. Furthermore, EuK‐(SO3)Cy5‐mas3 allowed tumor identification in human prostate samples, underlining the translational potential of this novel tracer. Trial registration Approval for use of biological material for research purposes was provided by the Translational Research Board of the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital (NKI-AvL) under reference IRBm19-273 (22/10/2019).

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“…2 C, top image). Placement of the Cy5-specific click-on filter [ 27 ] or a filter wheel that facilitated (Fig. 2 B, *) easy switching between white light and Cy5 imaging mode (Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

et al. 2022

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Novel fluorescent GLUT1 inhibitor for precision detection and fluorescence image‐guided surgery in oral squamous cell carcinoma

Tian

Tang

Shi

et al. 2022

Intl Journal of Cancer

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Early detection and complete resection of oral squamous cell carcinoma (OSCC) are crucial to improving patient survival and prognosis. However, specifically targeted imaging probes for OSCC detection are limited. Our study aimed to synthesize a novel near-infrared fluorescence (NIRF) probe for precision detection and fluorescence image-guided surgery in OSCC. Bioinformatics data indicated that glucose transporter 1 (GLUT1) is highly expressed in patients with OSCC. We demonstrated high and specific GLUT1 expression upon immunohistochemical staining of samples from 20 patients with OSCC. The specific expression of GLUT1 was further validated in both human OSCC cell lines and OSCC tumor xenografts. Based on these findings, the GLUT1 inhibitor WZB117 was utilized to synthesize a novel NIRF imaging probe, WZB117-IR820. The fluorescence molecular imaging data revealed that WZB117-IR820 could specifically bind to the tumor areas in an orthotopic OSCC mouse model after intravenous injection and could be further applied for precision fluorescence image-guided surgery with no residual tumor in the orthotopic CAL27-fLUC mouse tumor model. For further clinical translational application in patients with OSCC, precise delineation of OSCC tumor areas was achieved after topical application of the WZB117-IR820 imaging probe and was validated by histopathological and immunohistochemical analyses. In conclusion, we synthesized a novel fluorescent imaging probe, WZB117-IR820, which has potential clinical applications for early detection and fluorescence image-guided surgery in OSCC with no observable toxicity.

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68Ga-EMP-100 PET/CT—a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma—first in-human biodistribution and imaging results

Mittlmeier

Todica

Gildehaus

et al. 2021

Eur J Nucl Med Mol Imaging

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Background 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. Methods Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. Results Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86–29.16)), followed by bone metastases (SUVmax 5.56 (0.97–15.85)), and lymph node metastases (SUVmax 3.90 (2.13–6.28)) and visceral metastases (SUVmax 3.82 (0.11–16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. Conclusion Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.

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Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

Cited by 8 publications

References 36 publications

Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

Novel fluorescent GLUT1 inhibitor for precision detection and fluorescence image‐guided surgery in oral squamous cell carcinoma

68Ga-EMP-100 PET/CT—a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma—first in-human biodistribution and imaging results

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