Biotechnological and Chemical Sciences in Diagnostics

IN VIVO DIAGNOSTICS: IMAGING PROBES

IN VIVO DIAGNOSTICS: IMAGING PROBES

Academic year 2023/2024

Sommario del corso

• Course objectives
• Results of learning outcomes
• Program
• Course delivery
• Learning assessment methods
• Suggested readings and bibliography
• Teaching tools
• Course card

Course objectives

This course contributes to the educational objectives of the preparatory area of the master degree course in Biotechnologies and chemistry in diagnostics and it is aimed at providing students with solid knowledge in the design and development of imaging probes for in vivo diagnostic, a core of the master degree. In particular, the course aims to provide students with:

- an introduction to interdisciplinary (chemical, biological, radiological) language and to the scientific methodologies related the dsign of imaging probes.

-an overview of the imaging probes available for the different imaging techniques, that are used in pre-clinical studies and in the clinical practice for the diagnosis of different pathologies (MRI, x-ray TC, OI, US, PAI). The general features and chemical properties of probes used for in vitro and in vivo diagnostic procedures will be elucidated as well as the specific characteristics related to the different imaging modalities.

- an in-depth knowledge into the methods for preparation and characterization of imaging probes, including knowledge of chemistry and biology.

- an in-depth knowledge into the relationships between imaging probes (used at preclinical and clinical level) and biological systems (macromolecules, cells, living organisms).

Results of learning outcomes

KNOWLEDGE AND UNDERSTANDING

Acquisition of strong theoretical and applicative skills concerning the fundamental principles of design, development, characterization of probes for the main imaging techniques will be learned (Magnetic Resonance Imaging, x-ray computed tomography, optical imaging, ultrasound imaging and photoacoustic imaging).

Acquisition of strong skills about the interaction of chemicals used as imaging probes and biological systems (macromolecules, cells, living organisms).

Acquisition of solid knowledge among the different classes of contrast agents with the aim of maximizing the attainable contrast and reducing side effects for the patient.

Understating the basic principles of Molecular Imaging and Theranostic with focus on biomedical applications.

APPLYING KNOWLEDGE AND UNDERSTANDING

Acquisition of the ability to analyze scientific papers and data about in vivo imaging, theranostic, molecular imaging and iamging probes.

Capability to apply the theoretical knowledge of chemistry, biology, radiology and pharmaceutical sciences to the design and charcaterization of innovagive imaging probes

MAKING JUDGEMENTS

Acquisition of aware judgment autonomy concerning evaluation and interpretation of experimental data in order to achieve strategic choices in unkonw situations.

COMMUNICATION SKILLS

Acquisition of oral and written communication skills and expertise, in English, as well as the ability to use graphical and formal languages.

LEARNING SKILLS.

Acquisition of autonomous learning capacity and self-assessment of preparation

SOFT SKILLS.

This course will contribute to the acquisition of several soft skilss as team-working, organization, collaboration, creativity, communication, Time management, Public speaking.

Program

• Introduction to in vivo diagnostic probes

  • History of diagnostics from histology to in vivo molecular imaging.

  • General features and chemical properties of in vivo probes.

  • Chemical structures of probes (small organic molecules, inorganic molecules, metal complexes, peptides and proteins, supramolecular adducts, nano-/micro-systems, etc…). 

• Introduction to Molecular Imaging

• Introduction to Theranostic probes

• The following classes of imaging Probes will be analyzed:

  • MRI Probes: Relaxation agents (T_1w and T_2w agents), Chemical Exchange and Saturation Transfer (CEST) and Magnetization Transfer Contrast (MTC) agents, Hyperpolarized agents, Heteronuclear Contrast Agents (19F, etc...), Other MRI probes (DWI, etc )

• Probes for Optical imaging

Basis of optical signal generation and detection

Endogenous optical signals (autofluorescence, absorption of Hemoglobin and biological phorphyrins, etc…)

Quencing and photobleacing

Inorganic probes (QDs, metallo-phorphyrins, metal chalcogenides, etc…)

Organic dyes (cyanines, etc…)

Fluorecent proteins (GFP, RFP, TR, etc…)

Other probes for optical imaging

Applications of optical probes in biomedicine (in vivo imaging, detection of nucleic acids in vitro, applications in cells systems, Point of Care Technology, etc…)

• Probes for Ultrasound imaging

Basis of US contrast generation and detection

Microbubbles

Nanobubbles and echogenic liposomes

Other probes for US

Application of US probes in biomedicine

• Probes for Photoacoustic imging

Basis of PAI contrast generation and detection

Endogenous PAI contrast agents (Hemoglobin, melanin, lipid, etc…)

Exogenous PAI probes: Organic probes (cyanines, etc…), Inorganic probes, other exogenous probes.

Application of PAI probes in biomedicine.

• Probes for x-ray computed thomography (CT)

Basis of CT contrast generation and detection

Probes based on metals (I, Ba, Sr, etc... ).

• Generalities about probes for other imaging techniques:

MPI (magnetic particle imaging)

IR (infra-red imaging) and SERS (Surface-enhanced Raman scattering imaging)

MS (mass spectrometry imaging)

cyTOF imaging

• Supramolecular adducts and nanosystems for imaging.

• Nano-/micro-systems for imaging (liposomes, PLGA, nanogels, MSNs, etc…).

• Active and passive targeting.

• Enhanced permeability and retention (EPR) effect.

• Multimodal and smart probes; responsive probes.

Course delivery

All the 9 CFU of the course will be delivered in presence. The teaching activities will mainly consist in frontal lessons. Integrative practical activities (8h, Prof. Francesca Reineri and Dott. Enza Di Gregorio) will be also carried out, in small groups, using the research imaging facilities at the Molecular Imaging Centre (https://www.cim.unito.it/website/) which will allow students to practice with the preparation and characterization of some of the imaging probes studied during the lessons. 

During the course, a group activity will be organized aimed at analyzing more in detail a specific topic related to the course. The group will be guided, in the framework a flipped classroom methodology, to the reading of scientific literature related to imaging probes, analyzing a specific problem. Then, the group will prepare an elaboration of results of the activity to be discussed with the class.

Learning assessment methods

The final exam will be an oral and it will focuse mainly on the theoretical aspects of the course, in order to evaluate both the understanding of the fundamental properties of imaging probes and their applications. The student's ability to apply these principles to real contexts will be strongly assessed.

The group activity will be also considered in the final evaluation, with specific focus in analysing the ability to use formal language and the development of soft skills like team-working, organization, collaboration, creativity, communication, time management, public speaking.

For the preparation, students can use slides and notes.

Papers and reviews related to imaging probes will be suggested by the teacher during the course.

Some book are available for further study if deemed appropriate by the students:

• Molecular Imaging.Principles and Practice. 2nd Edition - August 2, 2021 Editors: Brian Ross, Sanjiv Gambhir

• Molecular Imaging Probes for Cancer Research September 2012 Edited By Xiaoyuan Chen (National Institutes of Health, USA)

• Contrast Agents for MRI: Experimental Methods (ISSN) (English Edition)- Edited by Valérie C Pierre  and Matthew J Allen. RSC.

• Ultrasound Contrast Agents: Targeting and Processing Methods For Theranostics. Paradossi, Pellegretti, Turco. Ed. Springers

• Liposomes in Analytical Methodologies edited by Katie A. Edwards. CRC Press

• Taylor & Francis Group

• Jonathan W. Steed, David R. Turner, Karl J. Wallace, ¸Core Concepts in Supramolecular Chemistry and Nanochemistry; Wiley, 2007.

• JW Steed, JL Atwood Supramolecular Chemistry, Wiley, 2009.

• RR Crichton Biological Inorganic Chemistry, Elsevier, 2013.

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