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A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions.

ABSTRACT: This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, obtained by conjugating the protein with the macrocyclic chelating agent DOTA through a one-pot reaction in aqueous medium. The product has been fully characterized and is stable to the thermal conditions adopted for labeling; after radiolabeling with longer half-life radionuclides such as ¹⁷⁷Lu or ¹¹¹In, it has shown radiochemical purity (RCP) >90% and resulted stable when stored in saline or plasma for 6 days at 37?°C. A ?PET/CT study, performed in vivo on adult female rats, showed that the radioactivity of HAC labeled with ⁶⁴Cu remained located in the mammary glands for at least 40?h, without diffusion or drainage in healthy tissues or in the lymphatic circulation. This new imaging agent might make the ROLL procedure more accessible, safe and flexible, promoting a significant time and cost reduction of this intervention. Moreover, HAC might also be used in other radio-guided surgical procedures in oncology.

SUBMITTER: Caviglioli G

PROVIDER: S-EPMC6449347 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions.

Caviglioli Gabriele G Chinol Marco M Baldassari Sara S Garaboldi Lucia L Zuccari Guendalina G Petretto Andrea A Drava Giuliana G Sinico Chiara C Paganelli Giovanni G

Scientific reports 20190404 1

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, ...[more]

PMID: 30948744

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Project description:Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms. Biofilm-related infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation of surrounding tissue. To date, no clinical solution that allows to efficiently prevent bacterial infection while promoting correct implant integration, has been developed. In this study, we demonstrated for the first time, to our knowledge that the physical immobilization of 1 and 5% human serum albumin (HSA) onto the surface of 3D printed macro- and microporous mPCL scaffolds, resulted in a reduction of Staphylococcus aureus colonization by 71.7 ± 13.6% and 54.3 ± 12.8%, respectively. Notably, when treatment of scaffolds with HSA was followed by tannic acid (TA) crosslinking/stabilization, uniform and stable coatings with improved antibacterial activity were obtained. The HSA/TA-coated scaffolds were shown to be stable when incubated at physiological conditions in cell culture media for 7 days. Moreover, they were capable of inhibiting the growth of S. aureus and Pseudomonas aeruginosa, two most commonly found bacteria in breast implant infections. Most importantly, 1%HSA/10%TA- and 5%HSA/1%TA-coated scaffolds were able to reduce S. aureus colonization on the mPCL surface, by 99.8 ± 0.1% and 98.8 ± 0.6%, respectively, in comparison to the non-coated control specimens. This system offers a new biomaterial strategy to effectively translate the prevention of biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

Project description:BackgroundIntraoperative Cerenkov luminescence imaging (CLI) is a novel technique to assess surgical margins in patients undergoing nerve sparing radical prostatectomy (RP). Here, we analyze the efficacy of a 550-nm optical short-pass filter (OF) to improve its performance.MethodsIn this prospective single-center feasibility study ten patients with prostate cancer (PC) were included between December 2019 and April 2020, including three patients without tracer injection as a control group. After preoperative injection of 68-Ga-prostate-specific membrane antigen (PSMA)-11 followed by RP, CLI of the excised prostate and the incised index lesion was performed to visualize the primary tumor lesion. We compared the findings on intraoperative CLI to postoperative histopathology. Furthermore, CLI-intensities determined as tumor to background ratio (TBR) and contrast to noise ratio (CNR) were measured.ResultsHistopathology proved positive surgical margins (PSM) in 3 patients with corresponding findings in CLI. After magnetic resonance imaging (MRI)-informed incision above the index lesion 2 out of 3 prostates demonstrated elevated CLI signals with histopathological confirmation of PC cells. The use of the OF enabled a significant reduction of the area of the regions of interest from a median of 1.80 to 0.15 cm2 (reduction by 85%, P=0.005) leading to increased specificity. Signals due to PSMs were not suppressed by the 550-nm OF. The median TBR was reduced from 3.33 to 2.10. In all three patients of the control group elevated CLI intensities were detected at locations with diathermal energy deposition during surgery. After application of the 550-nm OF these were almost totally suppressed with a TBR of 1.10. Measurements of Cerenkov luminescence intensity with the 550-nm OF showed a significant Pearson's correlation of 0.82 between PSM and the elevated TBR (P=0.003) and a significant Pearson's correlation of 0.66 between PSM and elevated CNR (P=0.04). Measurements without the OF did not correlate significantly.ConclusionsIntraoperative 68-Ga-PSMA CLI in PC is a tool that warrants further investigation to visualize PSM especially in intermediate and high-risk PC. Intraoperative CLI benefits from usage of a 550-nm OF to reduce false-positive signals.

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A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions.

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A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions.

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