MARIANO PONTICO

Dottore

ciclo: XXXIV


tutor: Prof. Roberto Pani

Titolo della tesi: PET and MR Thermometry imaging–guided photothermal therapy assisted by radiolabeled keratin-coated gold nanoparticles for precision anticancer thermoablation

Nanomedicine is an emerging key technology of the 21st century. Gold nanoparticles (AuNPs) have been actively investigated as photothermal converters, drug delivery systems, radiosensitizers, and molecular imaging probes in a wide range of biomedical applications in both cancer diagnostics and therapeutics. The flourishing development of AuNPs applications has led to the opportunity of a new targeted cancer treatment that could be capable of selectively fighting cancerous cells, keeping low harmful side effects suffered by surrounding healthy cells, namely the plasmonic photothermal therapy (PPTT). The PPTT approach should have the following key features: targeted AuNPs delivery to the tumor for effective thermal damage response under NIR laser exposure, aiming to keep the surrounding tissues healthy and accurate thermal dose calculation with non-invasive real-time monitoring of thermometric response profile in the target volume. What constitutes a technological frontier is the application of a novel AuNPs generation properly labeled with a radiotracer which may serve as a nuclear imaging-guided high-precision cancer probe. The topic of this thesis is part of a wider funded project (NANO-TAFT), focused on the development of a novel radiolabeled AuNPs-mediated selective PPPT cancer treatment, supported by the development of a prototypal multimodality PET/MR imaging integration console, using MR Thermometry (MRT) to provide a volumetric "heat map". The aims of my research work were to obtain accurate modeling of PET performance variability in detecting radiolabeled AuNPs and their concentration through a PET imaging phantom study carried out on three different PET systems, and the AuNPs radiolabeling, its further characterization, and nuclear imaging study. The evaluation of the variability of the efficiencies and of the AuNP concentration for each PET machine was done through the study of a phantom model and the standardized uptake value (SUV) calculation, which resulted in PET imaging poor reproducibility in terms of quantitative analysis and determination of concentrations. SPECT is known to be a more versatile and reliable imaging technique, thus it was chosen to use technetium-99m (99mTc) as labeling radionuclide along with SPECT technique, instead of fluorine-18 (18F) with PET imaging. A critical issue must be identified in the achievement of an effective AuNPs radiolabeling, able to demonstrate optimal radiochemical yield and stability performances. A novel bridging molecule, namely keratin, was used to solve the problem of binding AuNPs and radioisotopes. To our knowledge, keratin protein remains still unexplored in the field of PPPT-based applications. A reliable and reproducible procedure for the 99mTc radiolabeling of this novel generation of AuNPs (Ker-AuNPs) was therefore achieved. Optical, spectroscopic, and morphological analysis of the Ker-AuNPs proved their stable bioconjugation. The optimal radiolabeling strategy to obtain 99mTc-KerAuNPs and its relative conditions have been found and validated, leading to an excellent performance in terms of radiolabeling efficiency, that reach over 95% of radiochemical purity (RCP). UV-Vis absorbance test supported the occurrence of a novel Ker-AuNPs configuration. The laser-triggered photothermal test demonstrated a good thermometric response through a significant temperature increase in the site of 99mTc-Ker-AuNPs deposition, while corroborating the successful outcomes of the Ker-AuNPs radiolabeling procedure. SPECT imaging study showed a good performance. The analysis of PET imaging data on phantoms showed that PET is not sufficiently selective in terms of achievable spatial resolution and in the determination of the concentrations, thus its application in the context of this project has proven to be unfeasible. SPECT technique allows a less variable determination of radioisotope concentrations than PET and also a less complex calibration of SPECT equipment. Unfortunately, if reasonably small tumors are considered, both techniques are not able to ensure a proper high spatial resolution, which is a crucial prerequisite for a selective and safe treatment. Despite open issues related to the imaging applications remain unsolved, nuclear imaging techniques will be useful rather to determine the targeted volumes of interest, which subsequently will be more accurately confirmed by MR imaging, which has the absolute advantage of a better spatial resolution. A novel functional and stable AuNPs keratin coating has been provided, leading to a promising novel tool in the field of biocompatible photothermal nanoagents for selective anticancer PPPT treatments.

Produzione scientifica

  • 11573/935914 - 2015 - Differential influence of carotid stenosis and white matter disease on motor and cognitive activation (01a Articolo in rivista)
    CALISTRI, VALENTINA; TINELLI, EMANUELE; ACETI, ANTONIO; PONTICO, MARIANO; TARDIOLI, STEFANO; FIORELLI, MARCO; SPEZIALE, FRANCESCO; CARAMIA, FRANCESCA
  • 11573/1105232 - 2018 - 99mTc-HMPAO brain SPECT in the monitoring of cerebral vasculitis therapy (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; MORREALE, MANUELA; PONTICO, MARIANO; FRANCIA, ADA; DRUDI, FRANCESCO MARIA; FARCOMENI, ALESSIO; LIBERATORE, MAURO
  • 11573/1122133 - 2016 - Use of 123I-MIBG SPECT in association with 123I-FP-CIT in patients with Early Parkinson’s Disease: a new point of view. (04d Abstract in atti di convegno)
    FRANTELLIZZI, VIVIANA; ULLO, MARIA CRISTINA; FOLLACCHIO, GIULIA ANNA; PONTICO, MARIANO; RICCI, MARIA; SOLLAKU, SAADI; BERLOCO, BIANCA; FILAURI, MARTINA; LIBERATORE, MAURO; MONTELEONE, FRANCESCO; DE VINCENTIS, GIUSEPPE
  • 11573/1253342 - 2018 - Long-term chronic suppressive antibiotic therapy (CSAT) in chronic joint infection evaluated by (99m)Tc-HMPAO radiolabeled leucocytes scintigraphy (LS) (04d Abstract in atti di convegno)
    RICCI, MARIA; FOLLACCHIO, GIULIA ANNA; PONTICO, MARIANO; DE FEO, MARIA SILVIA; MONTELEONE, FRANCESCO; DE VINCENTIS, GIUSEPPE; CECCARELLI, GIANCARLO; LIBERATORE, MAURO
  • 11573/1255221 - 2017 - 223Radium: analysis of effect of treatment in bone oligo-metastatic CRPC patients (04d Abstract in atti di convegno)
    FRANTELLIZZI, VIVIANA; FOLLACCHIO, GIULIA ANNA; PONTICO, MARIANO; COSMA, LAURA; FARCOMENI, ALESSIO; MONTELEONE, FRANCESCO; DE VINCENTIS, GIUSEPPE
  • 11573/1255216 - 2017 - Rare paranganglioma localizations caught by MRI and CT hybrid 123I-MIBG SPECT imaging. (04d Abstract in atti di convegno)
    PONTICO, MARIANO; FOLLACCHIO, GIULIA ANNA; FRANTELLIZZI, VIVIANA; COSMA, LAURA; RICCI, MARIA; LIBERATORE, MAURO; MONTELEONE, FRANCESCO; DE VINCENTIS, GIUSEPPE
  • 11573/1255215 - 2017 - Effectiveness of long-term chronic suppressive antibiotic therapy in chronic joint infection: follow-up by 99mTc-HMPAO-labeled leukocyte scan (04d Abstract in atti di convegno)
    RICCI, MARIA; PONTICO, MARIANO; FOLLACCHIO, GIULIA ANNA; DE FEO, MARIA SILVIA; MONTELEONE, FRANCESCO; DE VINCENTIS, GIUSEPPE; CECCARELLI, GIANCARLO; LIBERATORE, MAURO
  • 11573/1255226 - 2017 - Definition of a Predictive Score to guide therapeutic management in metastatic CRPC patients eligible to Radium-223 (04d Abstract in atti di convegno)
    FOLLACCHIO, GIULIA ANNA; FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE FEO, MARIA SILVIA; MONTELEONE, FRANCESCO; LIBERATORE, MAURO; FARCOMENI, ALESSIO; PACILIO, MASSIMILIANO; DE VINCENTIS, GIUSEPPE
  • 11573/645668 - 2014 - Non mass-like enhancement categories detected by breast MRI and histological findings (01a Articolo in rivista)
    BALLESIO, LAURA; DI PASTENA, FRANCESCA; GIGLI, SILVIA; D'AMBROSIO, ILARIA; PONTICO, MARIANO; MANGANARO, LUCIA; PORFIRI, LUCIO MARIA; TARDIOLI, STEFANO
  • 11573/1336248 - 2018 - Annual Congress of the European Association of Nuclear Medicine October 13 - 17, 2018 Düsseldorf, Germany (04d Abstract in atti di convegno)
    FRANTELLIZZI, VIVIANA; SOLLAKU, SAADI; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1336242 - 2020 - Analysis of unusual adverse effects after radium-223 dichloride administration (01i Case report)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; PANI, ROBERTO; DE VINCENTIS, GIUSEPPE
  • 11573/1380770 - 2017 - Mixed leukocytes separation for scintigraphic purposes: assessment of red blood cells contamination (04d Abstract in atti di convegno)
    CIVITELLI, LIANA; PONTICO, MARIANO; FRANTELLIZZI, VIVIANA; FOLLACCHIO, GIULIA ANNA; D'ARCANGELO, ISABELLA; LIBERATORE, MAURO
  • 11573/1355420 - 2018 - 223Ra-dichloride Treatment In mCRPC Patients: Analysis Of An Elderly Population (04d Abstract in atti di convegno)
    FRANTELLIZZI, VIVIANA; SOLLAKU, SAADI; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1355376 - 2016 - Role of 99mTc-HMPAO brain perfusion SPECT in the clinical management of autoimmune brain vasculitis. (04d Abstract in atti di convegno)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; FARCOMENI, ALESSIO; FRANCIA, ADA; MORREALE, MANUELA; DE VINCENTIS, GIUSEPPE; LIBERATORE, MAURO
  • 11573/1364432 - 2020 - New frontiers in molecular imaging with superparamagnetic iron oxide nanoparticles (SPIONs): efficacy, toxicity, and future applications (01g Articolo di rassegna (Review))
    FRANTELLIZZI, VIVIANA; CONTE, MIRIAM; PONTICO, MARIANO; PANI, ROBERTO; DE VINCENTIS, GIUSEPPE
  • 11573/1364434 - 2020 - Role of nuclear imaging in cardiac amyloidosis management: clinical evidence and review of literature (01g Articolo di rassegna (Review))
    FRANTELLIZZI, VIVIANA; COSMA, LAURA; PONTICO, MARIANO; CONTE, MIRIAM; DE ANGELIS, CRISTINA; DE VINCENTIS, GIUSEPPE
  • 11573/1364439 - 2020 - Usefulness of 5 minutes 123I-mIBG scan in Parkinson's disease and heart failure (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; RICCI, MARIA; FARCOMENI, ALESSIO; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1383582 - 2020 - Baseline quality of life predicts overall survival in patients with mCRPC treated with 223Ra-dichloride (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; DE FEO, MARIA SILVIA; DI ROCCO, ARIANNA; PONTICO, MARIANO; FARCOMENI, ALESSIO; COSMA, LAURA; LAZRI, JULIA; DE VINCENTIS, GIUSEPPE
  • 11573/1383585 - 2021 - 123I-FP-CIT brain SPECT findings in succinic semialdehyde dehydrogenase (SSADH) deficiency (01i Case report)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE FEO, MARIA SILVIA; DE VINCENTIS, GIUSEPPE
  • 11573/1392115 - 2020 - Characterization of monolithic GAGG:Ce coupled to both PMT and SiPM array for gamma imaging in nuclear medicine (04c Atto di convegno in rivista)
    PANI, ROBERTO; BETTIOL, MARCO; LONGO, MARIACONCETTA; POLITO, CLAUDIA; FALCONI, RITA; DE SIO, LUCIANO; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE; PELLEGRINI, ROSANNA; FRANTELLIZZI, VIVIANA
  • 11573/1441881 - 2020 - Bone pain palliation outcomes and possibility of Radium-223 re-treatment in mCRPC (01i Case report)
    FRANTELLIZZI, VIVIANA; LAZRI, JULIA; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1455285 - 2020 - 111In-Octreoscan SPECT/CT hybrid imaging and 68Ga-DOTANOC PET/CT in neuroendocrine adenoma of the middle ear (NAME) (01i Case report)
    PONTICO, MARIANO; FRANTELLIZZI, VIVIANA; COSMA, LAURA; DE VINCENTIS, GIUSEPPE
  • 11573/1476172 - 2021 - The prognostic value of 123I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review (01g Articolo di rassegna (Review))
    PONTICO, MARIANO; BRUNOTTI, GABRIELE; CONTE, MIRIAM; CORICA, FERDINANDO; COSMA, LAURA; DE ANGELIS, CRISTINA; DE FEO, MARIA SILVIA; LAZRI, JULIA; MATTO, ANTONIO; MONTEBELLO, MELISSA; DI ROCCO, ARIANNA; FRANTELLIZZI, VIVIANA; FARCOMENI, ALESSIO; DE VINCENTIS, GIUSEPPE
  • 11573/1364424 - 2020 - Primary radical prostatectomy or ablative radiotherapy as protective factors for patients with mCRPC treated with radium-223 dichloride: an Italian multicenter study (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1545051 - 2021 - Unexpected detection of abscessualized lung carcinoma on tc-99m-hmpao-labeled leukocytes scintigraphy misdiagnosed on chest computed tomography (01i Case report)
    COSMA, LAURA; FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1159384 - 2018 - Bladder wall paraganglioma located using123I-mIBG SPECT and CT imaging (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; LETIZIA, CLAUDIO; DE VINCENTIS, GIUSEPPE
  • 11573/1145404 - 2018 - Incidental findings in traditional nuclear medicine practice (01i Case report)
    DE VINCENTIS, GIUSEPPE; PONTICO, MARIANO; RICCI, MARIA; FRANTELLIZZI, VIVIANA; LIBERATORE, MAURO
  • 11573/1568718 - 2021 - 89Zr-PET imaging in humans: a systematic review (01g Articolo di rassegna (Review))
    DE FEO, MARIA SILVIA; PONTICO, MARIANO; FRANTELLIZZI, VIVIANA; CORICA, FERDINANDO; DE CRISTOFARO, FLAMINIA; DE VINCENTIS, GIUSEPPE
  • 11573/1548008 - 2020 - Radium-223 in mCPRC patients: a large real-life Italian multicenter study (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1545054 - 2021 - Prognostic and theranostic applications of positron emission tomography for a personalized approach to metastatic castration‐resistant prostate cancer (01g Articolo di rassegna (Review))
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE FEO, MARIA SILVIA; CORICA, FERDINANDO; MONTEBELLO, MELISSA; DE VINCENTIS, GIUSEPPE
  • 11573/1590335 - 2021 - Radium-223 treatment in mcrpc patient with polycythemia vera (01i Case report)
    DE ANGELIS, CRISTINA; FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE FEO, MARIA SILVIA; LAZRI, JULIA; DE VINCENTIS, GIUSEPPE
  • 11573/1573683 - 2021 - Administrative health claims and laboratory data to identified mCRPC or mCSPC patients: the way to go looks long but promising (01f Lettera, Nota)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE
  • 11573/1590328 - 2021 - Potential prognostic value of miR-132 and miR-212 expression in mCRPC patients (01f Lettera, Nota)
    PONTICO, MARIANO; FRANTELLIZZI, VIVIANA; DE VINCENTIS, GIUSEPPE
  • 11573/1613110 - 2021 - 99mTc-labeled Keratin-coated gold nanoparticles for selective anticancer photothermal therapy (04b Atto di convegno in volume)
    FRANTELLIZZI, VIVIANA; PONTICO, MARIANO; DE VINCENTIS, GIUSEPPE; CIVITELLI, LIANA; PANI, ROBERTO; CALOGERO, ANTONELLA; DE SIO, LUCIANO
  • 11573/1652733 - 2022 - 99mTc-labeled keratin gold-nanoparticles in a nephron-like microfluidic chip for photo-thermal therapy applications (01a Articolo in rivista)
    FRANTELLIZZI, VIVIANA; VERRINA, VANESSA; PONTICO, MARIANO; MIGLIETTA, SELENIA; ROSA, PAOLO; SCIBETTA, SOFIA; PETROZZA, VINCENZO; DE FEO, MARIA SILVIA; DE VINCENTIS, GIUSEPPE; CALOGERO, ANTONELLA; PANI, ROBERTO; DE SIO, LUCIANO

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