Discovery and Application of New Radioactive Diagnostic Tools

Integrins are cell surface receptors playing essential roles in many physiological and pathological events. The relevance of RGD-dependent α_Vβ₃, α_Vβ₅, α_Vβ₆ and α₅β₁ integrins during tumour/fibrosis development and during tumor metastasisand angiogenesis is well established.

In recent years our efforts in the area of specific integrin ligands led to the development of a new series of g-aminocyclopentanecarboxylic acid (Acpca)-based or aminoproline (Amp)-based RGD-cyclotetrapeptides which turned out to be very potent α_Vβ₃, α_Vβ₅ and α₅β₁ integrin binders with IC₅₀ binding affinities in the nanomolar range. In particular, the covalent conjugation of our AmpRGD ligands with diagnostic probes such as fluorescent probes or metal-chelating units (e.g. DOTA), were accomplished and biological properties of these bioconjugates were evaluated with encouraging results.

Focus of this research line is on the design, synthesis, and characterisation of novel and modulable integrin-targeted RGD-based pseudopeptide ligands and their conjugates for molecular recognition a in the field of tumor/fibrosis non-invasive diagnosis.

Most recently, our interest has also turned towards the field of the optical imaging, more precicesly regarding the diagnosis of the Idiopathic Pulmonary Fibrosis (IPF) and the overespressed receptor of this pathology.

Main publications and patents about this subject:

1. Valtorta, S.; Toscani, D; Chiu, M.; Sartori, A; Coliva, A.; Brevi, C; Taurino, G.; Grioni, M.; Ruffini, L.; Vacondio, F.; Zanardi, F.; Bellone, M.; Moresco, R.M.; Bussolati, O. and Giuliani, N. [18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma, Frontiers in Oncology, 2021, 11, 760732. https://doi.org/10.3389/fonc.2021.760732

2. Sartori, A.; Bianchini, F.; Migliari, S.; Burreddu, P.; Curti, C.; Vacondio, F.; Arosio, D.; Ruffini, L.; Rassu, G.; Calorini, L.; Pupi, A.; Zanardi, F.; Battistini, L. Synthesis and Preclinical Evaluation of a Novel, Selective ¹¹¹In-labelled Aminoproline-RGD-peptide For Non-invasive Melanoma Tumor Imaging. Med. Chem. Commun. 2015, 6, 2175-2183. doi.org/10.1039/C5MD00301F