Radio-Guided Surgery with β− Radiation: Tests on Ex-Vivo Specimens

2018 ◽  
pp. 693-697
Author(s):  
C. Mancini-Terracciano ◽  
V. Bocci ◽  
M. Colandrea ◽  
F. Collamati ◽  
M. Cremonesi ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Guided Surgery

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

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2674
Author(s):  
Tessa Buckle ◽  
Maarten van Alphen ◽  
Matthias N. van Oosterom ◽  
Florian van Beurden ◽  
Nina Heimburger ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Oral Cavity Cancer ◽  
Ex Vivo ◽  
Intermediate Step ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Tumor Identification ◽  
Imaging Results ◽  
Pathological Evaluation ◽  
Fluorescence Camera

Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8–3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer.

scholarly journals [OA109] Validation of a radio-guided surgery technique based on beta-radiation: Test on ex-vivo specimens

2018 ◽  
Vol 52 ◽  
pp. 42
Author(s):  
Elena Solfaroli Camillocci ◽  
Carlo Mancini-Terracciano ◽  
Emilio Bertani ◽  
Valerio Bocci ◽  
Marzia Colandrea ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Beta Radiation ◽  
Guided Surgery ◽  
Surgery Technique ◽  
Radiation Test

scholarly journals Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984 ◽  
Author(s):  
Dmitry M. Polikarpov ◽  
Douglas H. Campbell ◽  
Lucinda S. McRobb ◽  
Jiehua Wu ◽  
Maria E. Lund ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Near Infrared ◽  
Ex Vivo ◽  
Extent Of Resection ◽  
Fluorescent Imaging ◽  
Control Group ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Specific Accumulation

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

Influence of dexamethasone on visible 5-ALA fluorescence and quantitative protoporphyrin IX accumulation measured by fluorescence lifetime imaging in glioblastomas: is pretreatment obligatory before fluorescence-guided surgery?

2021 ◽  
pp. 1-9
Author(s):  
Lisa I. Wadiura ◽  
David Reichert ◽  
Veronika Sperl ◽  
Alexandra Lang ◽  
Barbara Kiesel ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
Aminolevulinic Acid ◽  
Ex Vivo ◽  
Protoporphyrin Ix ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Significant Difference ◽  
The Mean

OBJECTIVE Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is nowadays widely applied for improved resection of glioblastomas (GBMs). Initially, pretreatment with dexamethasone was considered to be essential for optimal fluorescence effect. However, recent studies reported comparably high rates of visible fluorescence in GBMs despite absence of dexamethasone pretreatment. Recently, the authors proposed fluorescence lifetime imaging (FLIM) for the quantitative analysis of 5-ALA–induced protoporphyrin IX (PpIX) accumulation. The aim of this study was thus to investigate the influence of dexamethasone on visible fluorescence and quantitative PpIX accumulation. METHODS The authors prospectively analyzed the presence of visible fluorescence during surgery in a cohort of patients with GBMs. In this study, patients received dexamethasone preoperatively only if clinically indicated. One representative tumor sample was collected from each GBM, and PpIX accumulation was analyzed ex vivo by FLIM. The visible fluorescence status and mean FLIM values were correlated with preoperative intake of dexamethasone. RESULTS In total, two subgroups with (n = 27) and without (n = 20) pretreatment with dexamethasone were analyzed. All patients showed visible fluorescence independent from preoperative dexamethasone intake. Furthermore, the authors did not find a statistically significant difference in the mean FLIM values between patients with and without dexamethasone pretreatment (p = 0.097). CONCLUSIONS In this first study to date, the authors found no significant influence of dexamethasone pretreatment on either visible 5-ALA fluorescence during GBM surgery or PpIX accumulation based on FLIM. According to these preliminary data, the authors recommend administering dexamethasone prior to fluorescence-guided surgery of GBMs only when clinically indicated.

scholarly journals The β- radio-guided surgery: Method to estimate the minimum injectable activity from ex-vivo test

2019 ◽  
Vol 58 ◽  
pp. 114-120 ◽  
Author(s):  
A. Russomando ◽  
M. Schiariti ◽  
V. Bocci ◽  
M. Colandrea ◽  
F. Collamati ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Guided Surgery

MHz-OCT for low latency virtual reality guided surgery: first wet lab experiments on ex-vivo porcine eye

2019 ◽  
Author(s):  
Yoko Miura ◽  
Wolfgang Draxinger ◽  
Christin Grill ◽  
Tom Pfeiffer ◽  
Salvatore Grisanti ◽  
...  
Keyword(s):  
Virtual Reality ◽  
Ex Vivo ◽  
Low Latency ◽  
Guided Surgery ◽  
Lab Experiments ◽  
Surgery First ◽  
Wet Lab

scholarly journals Evaluation of Ac-Lys0(IRDye800CW)Tyr3-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma

2021 ◽  
Author(s):  
Bianca M. Dijkstra ◽  
Marion de Jong ◽  
Marcus C. M. Stroet ◽  
Fritz Andreae ◽  
Sebastiaan E. Dulfer ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Ex Vivo ◽  
Specific Binding ◽  
Somatostatin Receptor ◽  
Receptor Subtype ◽  
Tumor Uptake ◽  
In Vivo Models ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Molecular Fluorescence

Abstract Purpose Meningioma recurrence rates can be reduced by optimizing surgical resection with the use of intraoperative molecular fluorescence guided surgery (MFGS). We evaluated the potential of the fluorescent tracer 800CW-TATE for MFGS using in vitro and in vivo models. It targets somatostatin receptor subtype 2 (SSTR2), which is overexpressed in all meningiomas. Methods Binding affinity of 800CW-TATE was evaluated using [177Lu] Lu-DOTA-Tyr3-octreotate displacement assays. Tumor uptake was determined by injecting 800CW-TATE in (SSTR2-positive) NCI-H69 or (SSTR2-negative) CH-157MN xenograft bearing mice and FMT2500 imaging. SSTR2-specific binding was measured by comparing tumor uptake in NCI-H69 and CH-157MN xenografts, blocking experiments and non-targeted IRDye800CW-carboxylate binding. Tracer distribution was analyzed ex vivo, and the tumor-to-background ratio (TBR) was calculated. SSTR2 expression was determined by immunohistochemistry (IHC). Lastly, 800CW-TATE was incubated on frozen and fresh meningioma specimens and analyzed by microscopy. Results 800CW-TATE binding affinity assays showed an IC50 value of 72 nM. NCI-H69 xenografted mice showed a TBR of 21.1. 800CW-TATE detection was reduced after co-administration of non-fluorescent DOTA-Tyr3-octreotate or administration of IRDye800CW. CH-157MN had no tumor specific tracer staining due to absence of SSTR2 expression, thereby serving as a negative control. The tracer bound specifically to SSTR2-positive meningioma tissues representing all WHO grades. Conclusion 800CW-TATE demonstrated sufficient binding affinity, specific SSTR2-mediated tumor uptake, a favorable biodistribution, and high TBR. These features make this tracer very promising for use in MFGS and could potentially aid in safer and a more complete meningioma resection, especially in high-grade meningiomas or those at complex anatomical localizations.

Tumor-non-tumor discrimination by a β- detector for Radio Guided Surgery on ex-vivo neuroendocrine tumors samples

2020 ◽  
Vol 72 ◽  
pp. 96-102 ◽  
Author(s):  
S. Morganti ◽  
E. Bertani ◽  
V. Bocci ◽  
M. Colandrea ◽  
F. Collamati ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Ex Vivo ◽  
Guided Surgery

scholarly journals Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 987
Author(s):  
Fortuné M.K. Elekonawo ◽  
Jan Marie de Gooyer ◽  
Desirée L. Bos ◽  
David M. Goldenberg ◽  
Otto C. Boerman ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Near Infrared ◽  
Ex Vivo ◽  
Tumor Resection ◽  
Human Tumor ◽  
Image Guided Surgery ◽  
Radioactive Label ◽  
Near Infrared Fluorescence ◽  
Guided Surgery ◽  
Image Guided

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

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