FLUODIAMON

Ultra-high resolution and ultra-sensitive fluorescence methods for objective sub-cellular diagnosis of early disease and disease progression in breast and prostate cancer

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'The overall objective of this proposal is to develop and validate a quantitative, minimally invasive diagnostic tool for early and conclusive detection, diagnosis and monitoring of disease and disease progression of breast and prostate cancer. A methodology will be developed making use of a combination of the probably most exciting recent advances in the field of light microscopy, for fluorescence-based optical imaging of individual sample cells. It includes advances which will take the spatial resolution far beyond the fundamental limits of optical resolution, the sensitivity down to an ultimate single-molecule level, and multi-parameter detection schemes significantly increasing the fluorescence information by which these cellular images can be analysed. Apart from detecting and identifying tumour markers in the samples, tumour-specific spatio-temporal molecular distributions within the intact sample cells will be exploited. This is to date an almost unexploited dimension of diagnostic information. By combining and supporting these novel optical methods with state-of-the-art affinity molecule biotechnology, , tumor biomarkers, fluorophore chemistry, and bioinformatic validation tools, all possible means will be exploited to extract a maximum amount of information out of very small amounts of sample material. We thereby expect that an improved, early and reliable diagnosis of breast and prostate cancer will be possible, from amounts of sample material small enough that a minimally invasive procedure such as Fine-needle aspiration (FNA) can be used. In addition, by the minimally invasive FNA-based sampling, serious sampling-related side-effects, such as seeding and spread of cancer cells can be completely avoided. Given the high incidence of breast and prostate cancer, and the utmost importance of an early and conclusive diagnosis for the prognosis of these diseases, the relevance of this project can not be overestimated.'

Introduzione (Teaser)

Early stage detection of breast and prostate cancer is crucial in order to further increase the survival rate of these patients. The EU funded a research initiative aimed at realising early breast and prostate cancer diagnosis using novel imaging and sampling methodologies that are safe and minimally invasive.

Descrizione progetto (Article)

Core needle biopsy used for sample collection carries the risk of cancer seeding due to trauma from needle penetration at the tumour site. Although, fine needle aspiration (FNA) cell sampling is minimally invasive, less risky, faster and cost efficient, sample quantity is often too sparse for conclusive results.

The FLUODIAMON project aimed to develop early cancer detection protocols that are safe and effective. This involved optimising the FNA sampling technique and image acquisition, resolution and specificity, identifying cancer biomarkers and standardising bioinformatics processing after validation.

Researchers developed FNA sampling needles with better ultrasound visibility for accurate positioning. Penetration and manoeuvrability were improved by adding computer-controlled oscillations and bevelling the needle tip. The results were validated based on data from more than 200 breast cancer patients. A fully functional anti-seeding instrument with a specialised anti-seeding needle was also developed and validated on patients.

Biomarkers found useful for the developed protocols and showing specific imaging features for breast and prostate cancer include vimentin and tubulin (cytoskeletal proteins), IGF1R, HER1, HER2 (membrane proteins), and Cyclin A and Cyclin E (cell cycle regulating proteins). Their spatial distribution patterns were studied in individual FNA sampled cells for the detection of malignant tumours.

Stimulated emission depletion (STED) microscopy and multi-parameter fluorescence detection imaging (MFDi) methods were developed for the study of sub-cellular FNA samples. For this purpose, highly photostable and bright fluorophores were used as labels and coupled to relevant protein biomarkers in imaging procedures.

Through bioinformatic quantitative analysis and verification, six independent diagnostic classifiers of malignant cancers were identified for their early detection. Knowledge gained was disseminated through 24 peer-reviewed articles, workshops and seminars, as well as on the website. Project members also applied for 10 specific patents.

The results from this project have opened the doors for safer, patient-friendly, minimally invasive early stage diagnostic and therapeutic treatment of most cancers. These methodologies could also be adapted for follow up of pre-malignant lesions or evaluating disease progress and response to therapy.