DREAMi

Harnessing the potential of the THP: moving toward the development of a clinical-grade kit for a peptide-based PET imaging agent for real-time imaging of aberrant c-Met cancers for another giant step in cancer treatment

Principal investigator: Silvia Panseri

Personnel involved: Monica Montesi, Noemi Ravaglia

Starting date: 16/10/2023
Duration: 24 months
Total funding: 261.437,00 € (CUP: B53D23020110006)
Action: PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR) Missione 4 “Istruzione e Ricerca” – Componente C2 Investimento 1.1, “Fondo per il Programma Nazionale di Ricerca e Progetti di Rilevante Interesse Nazionale (PRIN)” PRIN 2022 – D.D. 104 del 02/02/2022
CNR-ISSMC role: Partner
Coordinator: Dr. Giuseppe Floresta – Università di Catania
Consortium: 4 partners (Università degli Studi di Catania Dr. Floresta; ISSMC-CNR Dr. Panseri; Università degli studi “Magna Grecia” di Catanzaro Dr. Procopio; Università degli studi di Firenze Dr. Crocetti).

Prot. 2022BAN3TB

Aberrant hepatocyte growth factor/hepatocyte growth factor receptor (HGFR or c-Met) signalling is involved in the development of several tumour types. Knowledge of c-Met expression in real-time will assist in the diagnosis and in the monitoring of response to therapy. The overall objective of the project is to evaluate/produce a library of molecular agents able to effectively target c-Met and to efficiently bind gallium-68 and/or iodine-124/131, and therefore to be exploited as c-Met PET imaging tracers as well as theragnostic purposes. The agent structure will therefore consist of a protein that will locate the tissues affected by the disease, and of particular units that will bind the radioelement and make the cells visible in the positron emission tomography. The expected results of the project are to select the most promising and effective tracers among the library of synthesized compounds for further preclinical and clinical development. The objective will be achieved thanks to a rational design and synthesis of the novel peptides-based PET tracers. The cellular interactions of already produced c-Met sequences will be studied and novel chemistry for a convenient covalent bind of iodine to hydroxypiridinones (the radioactively labelled part of the probes) will be developed and radioevaluated. It is logical to believe that, in future clinical practice, non-invasive PET imaging with the developed tracers will support not only the diagnosis of c-Met overexpressed cancers but also the selection of patients for c-Met–targeting drugs (Met inhibitors and anti-Met antibodies), as well as identifying responding and nonresponding patients for such therapeutic agents.

Final Results

The project achieved its main objectives, demonstrating the feasibility of a novel platform of peptide-based theranostic agents targeting the c-Met receptor. Several peptide sequences and a library of Mypep conjugates were designed and synthesized, and subsequently characterized through biological and imaging studies. In vitro assays confirmed the absence of cytotoxicity at the concentrations tested and demonstrated the ability of the peptides to selectively recognize c-Met-positive cells. Successful conjugation with the THP chelator was achieved while preserving target interaction. The conjugates also showed efficient radiolabeling with ^68Ga under mild conditions, confirming their potential as PET imaging agents.

Direct iodination of the THP scaffold was instead found to be unfeasible; however, this limitation was overcome by exploiting tyrosine residues present in the peptide sequences, enabling the development of a strategy for dual labeling with gallium and iodine. Overall, the results obtained validate the initial concept and provide a solid experimental basis for the development of dual-labelled theranostic probes. The project also strengthened the interdisciplinary expertise of the participating research groups, creating the conditions for a subsequent phase of preclinical development. Future activities will focus on optimizing radioiodination, stability, and pharmacokinetic properties, followed by in vivo studies of biodistribution, targeting, and efficacy, with the ultimate goal of advancing these systems towards potential clinical application.

Dissemination of Results

Scientific publications

• Patamia, N. Ravaglia, M. Failla, E. Saccullo, E. Bruno, V. Abbate, M. Montesi, S. Panseri, G. Floresta. Anti-Invasive Peptide-Functionalized Nanotubes for Selective C-Met Targeting and Metal Chelation. ACS Omega. 2026, 11 (28): 42706–42715. doi.org/10.1021/acsomega.6c03987
• Patamia, E. Saccullo, M. Larocca, V. Fuochi, S. Furnari, P. M. Furneri, A. Cilibrizzi, G. Floresta. Engineered α-Helical Peptides with Chelating Agents as Approach to Antibacterial Therapeutics. ChemistryOpen 2026, 15(1), e202500588
• Patamia, E. Saccullo, L. Crocetti, A. Procopio, G. Floresta. Labeling Peptides with Radioiodine: An Overview of Traditional and Emerging Techniques. Applied sciences 2025, 15(14), 7803.
• Floresta. Leading designs of peptide-based chemical probes for medical imaging- the dawn of precision diagnostics Future Medicinal Chemistry 2025, 17(8), 861–863.
• Patamia, E. Saccullo, V. Fuochi, F. Magaletti, L. Trecarichi, S. Furnari, P. M. Furneri, V. Barbera, G. Floresta, A. Rescifina. Developing Advanced Antibacterial Alginic Acid Biomaterials through Dual Functionalization. ACS Applied Bio Materials 2024, 7(10), 6932–6940.
• Failla, A. Ferlazzo, V. Abbate, G. Neri, E. Saccullo, A. Gulino, A. Rescifina, V. Patamia, G. Floresta. THP as a sensor for the electrochemical detection of H2O2. Bioorganic Chemistry 2024, 152, 107721.

Conference presentations

1. Congresso Congiunto delle Sezioni Sicilia e Calabria della Società Chimica Italiana. Messina, 2-3 Dicembre 2024. From Waste to Resource: A Polysaccharide-Based Composite for Converting VOCs into Valuable CO2-derived Products. E. Saccullo, V. Patamia, A. Bifarella, A. Ferlazzo, C. Zagni, R. Fiorenza, A. Gulino, G. Floresta, A. Rescifina.
2. Conferimento premio al PI. XXVIII National Congress of Società Chimica Italiana- 26-30 Agosto 2024, Milano. Invited Lecture, Junior Scientific Research Award 2024 “Organic chemistry for life sciences” Exploring the Boundless Utility of Chelation Agents: From Therapeutics to Catalysis. G. Floresta.
3. Annual Meeting of the Italian Society for Biomaterials, SIB 2024. 8–10 July 2024 Faenza, Italy. Bio-Based Materials for Combating Bacterial Infections: Functionalization of Halloysite Nanotubes and Alginic Acid. V. Patamia, E. Saccullo, V. Fuochi, F. Magaletti, S. Furnari, P. M. Furneri, V. Barbera, G. Floresta, A. Rescifina.
4. Annual Meeting of the Italian Society for Biomaterials, SIB 2024. 8–10 July 2024 Faenza, Italy. Enhancing Cancer Imaging and Therapy with Peptide PET Tracers Targeting c-Met N. Ravaglia, M. Failla, L. Apolloni, M. Montesi, V. Abbate, G. Floresta, S. Panseri.
5. Invided lecture for the PI. Thematic Workshop focus on the “Evaluation of cell/biomaterial interaction” organized in the framework of the PREDICTOS project (N. 101079372 — HORIZON-WIDERA-2021-ACCESS-03). 17-18 June 2024, Faenza, Italy. Exploring the Versatile Applications of Hydroxypyranone and Hydroxypyridinone Derivatives: From Metal Chelation to Radiopharmaceuticals and Beyond. G. Floresta.
6. Invided lecture for the PI. CINMPIS days 2024. 7-9 February 2024, Bari, Italy. Hydroxypyranones and hydroxypyridinones: from imaging/biological uses to catalysis applications. G. Floresta, V. Patamia, E. Saccullo, M. Camarda, C. Zagni, A. Rescifina.
7. TISSUE ENGINEERING & REGENERATIVE MEDICINE INTERNATIONAL SOCIETY 2024 WORLD CONGRESS JUNE 25–28, 2024 / SEATTLE, WA SEATTLE CONVENTION CENTER. Peptide Pet Tracers Targeting C-met: Towards Enhanced Cancer Imaging And Therapy AUTHORS: N. Ravaglia, M. Failla, L. Apolloni, M. Montesi, V. Abbate, G. Floresta, S. Panseri.
8. Poster presentation at the School of Nanomedicine (9-11 October 2024) in Florence (IT)
9. Chemical Nanoscience Early Career Spring Symposium 2025 held at UCL Department of Chemistry, London, UK, on the 9-10th of April 2025.
10. 1st Edition of MiSuSPharmA Conference 5-6 May 2025, Naples
11. XLII Convegno Nazionale della Divisione di Chimica Organica CDCO 2025 Villasimius – Cagliari dal 21-25 settembre 2025. Dual-Labeled Peptide-Based Radiotracers Targeting c-Met for PET Imaging and Theragnostics in Cancer. V. Patamia, E. Saccullo, N. Ravaglia, L. Crocetti, A. Procopio, S. Panseri, G. Floresta.
12. Japanese – Italian Symposium on Organic Chemistry Bari 12-15 Ottobre, 2025. Chelating Agents as Versatile Platforms for Imaging, Theragnostics, and Catalysis. V. Patamia, E. Saccullo, N. Ravaglia, L. Crocetti, A. Procopio, S. Panseri, A. Rescifina, G. Floresta.
13. CONGRESSO CONGIUNTO SEZIONI CALABRIA E SICILIA Università della Calabria, 1 e 2 dicembre 2025 Centro Congressi “Beniamino Andreatta” Arcavacata di Rende (CS). HNT Nanoplatform: Integrated c-Met Targeting and PET Traceability V. Patamia, E. Saccullo, N.Ravaglia, M. Montesi, S. Panseri, A. Rescifina, G. Floresta.
14. Invito del PI a partecipare allo Strike (https://cordis.europa.eu/project/id/101072462) Meeting held from 9 to 10 February 2026 at Hotel San Antonio el Real in Segovia (Spain).
15. CINMPIS DAYS 2026 – Monastero dei Benedettini – Catania 16-18 Febbraio 2026. Bridging Nature and Advanced Technology through Multifunctional Biomimetic Materials. V. Patamia, E. Saccullo, E. G. Tomarchio, C. Zagni, V. Pistarà, G. Floresta, A. Rescifina.