PET data were acquired in list mode, using the full axial acceptance angle of the scanner (3D mode), and then reconstructed with the Expectation Maximization (EM) algorithm. (p.i.) in ex lover vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later occasions. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex lover vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to MCB-613 Caelyx and DOX-SiNPs treatment. Proteomics study recognized 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. Conclusion These findings exhibited a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles. strong class=”kwd-title” Keywords: HER2-positive BC, targeted silica nanoparticles, TZ-half chain conjugation, 99mTc-radiolabeling, SPECT imaging, doxorubicin-loaded nanoparticles Introduction Breast malignancy (BC) is the second leading cause of mortality for tumor after lung malignancy,1 and it has long been the predominant reason of cancer death among women.2 The phenotypic/genotypic heterogeneity of neoplastic populations within a patients tumor, and among different patients, are features that can complicate diagnosis and treatment setting. Several histopathological biomarkers, such as receptors expression (estrogen-receptor, progesterone-receptor and/or HER2), contribute to diagnostic classification.3,4 Treatment arranging, prognosis and responses to therapy reflect these expression profiles.5 It is well known that HER2 gene is amplified in about 30% of BC patients, and it is associated with aggressive phenotype and poorer clinical outcomes,6 making HER2 a relevant target for both diagnosis and therapy. Nowadays, the anti-HER2 monoclonal antibodies administration, such as trastuzumab (TZ), in combination with liposomal Doxorubicin (Caelyx) is considered the first-line treatment of metastatic/recurrent HER2-positive (HER2+) BC.7 Despite its efficacy, about 70% of HER2+ BC patients demonstrate resistance and systemic toxicity to this therapy setting,8 stressing the relevance of developing new effective and safe therapeutic strategies. The new drug TZ-emtansine (T-DM1), an antibody cytotoxic drug conjugated, has improved overall survival in patients with HER2+ metastatic BC, who were previously treated with TZ and Caelyx.9 In 2013, FDA first approved T-DM1 as monotherapy for the treatment of patients MCB-613 with HER2+ advanced BC, who experienced previously received TZ and taxane. 9 The security and efficacy of this novel agent in the BC setting, and its deficiency in the treatment of metastatic HER2+ BC, has been MCB-613 further assessed recently confirming some limitations.10,11 Nevertheless, to get advantages by TZ based therapies the HER2 expression evaluation remains crucial. Currently, BC diagnosis and screening are usually performed by anatomical or molecular in vivo diagnostic techniques, whereas tumor phenotype is usually evaluated through ex lover vivo immunohistochemical analysis of biopsy specimens MCB-613 from main lesion or regional lymph nodes.12 Staging and searching for metastases is only carried out in symptomatic patients, or in those at high risk for relapse.13 The prevalence of metastasis in asymptomatic Rabbit Polyclonal to DRP1 patients is high in large tumors or in patients with considerable nodal disease.14 Program staging and restaging consist of chest radiography, abdominal ultrasound, and bone scan, but only the latter technique owns good sensitivity, although it has showed low specificity and it is easy to cause false positives.15 New advances in molecular imaging techniques as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT),16 have progressed improving their accuracy for the identification of specific tumor biomarkers, such as HER2, in the different districts, discriminating pathological changing in non-invasive way.17 Hence, these techniques might provide.