In recent years, significant progress has been made in the field of oncology. These advancements are intricately linked to multidisciplinary approaches that have renewed precision medicine, seeking more innovative personalized therapies, as well as cutting-edge diagnostic methods. Unconventional radiotherapeutic modalities, including proton therapy, have notably enhanced the treatment of various aggressive tumors. However, the adequate therapy of such tumors remains a challenge that still requires further investigations. Concurrently, nuclear medicine approaches not only enable therapy but also facilitate the integration of diagnostic and therapeutic strategies, a concept known as theranostics. Theranostics introduces a novel concept, combined by “therapeutics” and “diagnostics”, indicating an unique chemical compound able of simultaneously providing both therapy and diagnosis. Our studies have explored innovative methods for diagnostic, therapeutic and theranostic approaches. Surrounded by the commonly used radionuclides, 68Ga is currently employed in clinical cancer diagnosis, especially for neuroendocrine and prostate tumors. Its short half-life, about 68 minutes, enables the patients to have a relatively brief radiation exposure during imaging procedures. Specifically, our investigations aimed at examining a novel 68Ga labeled radiopharmaceutical for diagnostic purposes, yielding promising results, with the assistance of radiomic and digital pathology analyses. In the pursuit of precision medicine, innovative approaches for therapy and theranostic are essential. Identifying a potential theranostic radionuclide and an innovative target were crucial steps toward addressing tumors that are currently tough to treat. The potential candidate for a theranostic radionuclide emerged as 111Ag. With γ and β- emissions and 7.45 days of half-life, 111Ag holds promise for diagnostic and theranostic applications. However, the necessity to find a compatible target for radioresistant cancer remains a formidable challenge. In our studies, a potential target was identified in Src, which is overexpressed in aggressive and radioresistant tumors. Hence, we evaluated the possibility of using a Src inhibitor, Si306, evaluating its labeling with Boron, currently applied for proton therapy studies. This investigation confirmed the ability of the molecule to maintain its adjuvant characteristics with proton therapy, despite the structural modification. While further studies are essential to validate our preliminary findings, the ultimate purpose of this study was to lay the foundation for innovative theranostic approaches for cancer. This includes exploring combinations with unconventional radiotherapies, including proton therapy, to target aggressive tumors, currently resistant to conventional therapies.
Negli ultimi anni, l’oncologia ha compiuto notevoli progressi, principalmente grazie all’impiego di approcci multidisciplinari, che hanno rinnovato la medicina di precisione nella ricerca di terapie personalizzate e metodi diagnostici all’avanguardia. Tra queste, le modalità radioterapeutiche non convenzionali, come la protonterapia, hanno migliorato sensibilmente il trattamento di alcune tipologie di cancro particolarmente aggressive. Tuttavia, il trattamento adeguato di tali tumori rimane una sfida che richiede ancora ulteriori approfondimenti. In parallelo, gli approcci di medicina nucleare non solo si concentrano sulla terapia oncologica, ma facilitano anche l’integrazione di strategie diagnostiche e terapeutiche, concetto noto come teranostica. La teranostica, infatti, si serve dell’utilizzo di composti chimici in grado di garantire entrambi gli approcci contemporaneamente. I nostri studi si sono quindi focalizzati sull’utilizzo di metodi innovativi per applicazioni diagnostiche, terapeutiche e teranostiche. Tra i radionuclidi comunemente utilizzati, il 68Ga è attualmente impiegato nella diagnosi clinica del cancro, in particolare per i tumori neuroendocrini e della prostata. La sua breve emivita, circa 68 minuti, consente ai pazienti di ricevere una dose radioattiva per un periodo di tempo limitato all’esecuzione delle procedure di imaging. Nello specifico, le nostre ricerche hanno previsto lo studio in vivo di un nuovo radiofarmaco marcato con 68Ga, ottenendo risultati di imaging promettenti mediante l'ausilio di analisi radiomiche e della patologia digitale. L'identificazione di un potenziale radionuclide teranostico e di un target molecolare innovativo sono degli elementi cruciali per l’avanzamento della medicina di precisione, soprattutto nella terapia di tumori attualmente difficili da trattare. In questo contesto, un potenziale radionuclide candidato alla teranostica è l’111Ag. Esso presenta infatti caratteristiche promettenti per applicazioni sia diagnostiche che terapeutiche. Tuttavia, la necessità di trovare un bersaglio innovativo per tumori aggressivi e radioresistenti rimane tuttora una sfida ardua. Tra gli oncogeni overespressi in tali tumori, Src è emerso come potenziale target molecolare. Per tale ragione, abbiamo valutato la possibilità di utilizzare un inibitore di Src, Si306, valutandone la marcatura con Boro, attualmente applicata per studi di protonterapia. Tale studio ha confermato la capacità della molecola di mantenere le sue caratteristiche coadiuvanti con la protonterapia, nonostante le modifiche strutturali. Sebbene siano essenziali ulteriori approfondimenti per convalidare i nostri risultati preliminari, lo scopo ultimo di questo studio è quello di gettare le basi per approcci teranostici innovativi da applicare in ambito oncologico. Ciò include la potenziale combinazione di trattamenti con composti radiomarcati e approcci radioterapici non convenzionali, tra cui la protonterapia, al fine di migliorare il trattamento di tumori aggressivi, attualmente resistenti alle terapie tradizionali.
Targeted therapy: strategie innovative per approcci teranostici / Pavone, ANNA MARIA. - (2024 Jun 14).
Targeted therapy: strategie innovative per approcci teranostici
PAVONE, ANNA MARIA
2024-06-14
Abstract
In recent years, significant progress has been made in the field of oncology. These advancements are intricately linked to multidisciplinary approaches that have renewed precision medicine, seeking more innovative personalized therapies, as well as cutting-edge diagnostic methods. Unconventional radiotherapeutic modalities, including proton therapy, have notably enhanced the treatment of various aggressive tumors. However, the adequate therapy of such tumors remains a challenge that still requires further investigations. Concurrently, nuclear medicine approaches not only enable therapy but also facilitate the integration of diagnostic and therapeutic strategies, a concept known as theranostics. Theranostics introduces a novel concept, combined by “therapeutics” and “diagnostics”, indicating an unique chemical compound able of simultaneously providing both therapy and diagnosis. Our studies have explored innovative methods for diagnostic, therapeutic and theranostic approaches. Surrounded by the commonly used radionuclides, 68Ga is currently employed in clinical cancer diagnosis, especially for neuroendocrine and prostate tumors. Its short half-life, about 68 minutes, enables the patients to have a relatively brief radiation exposure during imaging procedures. Specifically, our investigations aimed at examining a novel 68Ga labeled radiopharmaceutical for diagnostic purposes, yielding promising results, with the assistance of radiomic and digital pathology analyses. In the pursuit of precision medicine, innovative approaches for therapy and theranostic are essential. Identifying a potential theranostic radionuclide and an innovative target were crucial steps toward addressing tumors that are currently tough to treat. The potential candidate for a theranostic radionuclide emerged as 111Ag. With γ and β- emissions and 7.45 days of half-life, 111Ag holds promise for diagnostic and theranostic applications. However, the necessity to find a compatible target for radioresistant cancer remains a formidable challenge. In our studies, a potential target was identified in Src, which is overexpressed in aggressive and radioresistant tumors. Hence, we evaluated the possibility of using a Src inhibitor, Si306, evaluating its labeling with Boron, currently applied for proton therapy studies. This investigation confirmed the ability of the molecule to maintain its adjuvant characteristics with proton therapy, despite the structural modification. While further studies are essential to validate our preliminary findings, the ultimate purpose of this study was to lay the foundation for innovative theranostic approaches for cancer. This includes exploring combinations with unconventional radiotherapies, including proton therapy, to target aggressive tumors, currently resistant to conventional therapies.File | Dimensione | Formato | |
---|---|---|---|
Anna Maria Pavone_PhD thesis.pdf
embargo fino al 14/06/2025
Tipologia:
Tesi di dottorato
Licenza:
NON PUBBLICO - Accesso privato/ristretto
Dimensione
3.46 MB
Formato
Adobe PDF
|
3.46 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.