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1.
Nanomedicine ; 25: 102157, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31982616

RESUMO

Nanostructured lipid carriers (NLC) might represent an interesting approach for the identification and targeting of rupture-prone atherosclerotic plaques. In this study, we evaluated the biodistribution, targeting ability and safety of 64Cu-fonctionalized NLC in atherosclerotic mice. 64Cu-chelating-NLC (51.8±3.1 nm diameter) with low dispersity index (0.066±0.016) were produced by high pressure homogenization at tens-of-grams scale. 24 h after injection of 64Cu-chelated particles in ApoE-/- mice, focal regions of the aorta showed accumulation of particles on autoradiography that colocalized with Oil Red O lipid mapping. Signal intensity was significantly greater in aortas isolated from ApoE-/- mice compared to wild type (WT) control (8.95 [7.58, 10.16]×108 vs 4.59 [3.11, 5.03]×108 QL/mm2, P < 0.05). Moreover, NLC seemed safe in relevant biocompatibility studies. NLC could constitute an interesting platform with high clinical translation potential for targeted delivery and imaging purposes in atherosclerosis.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Lipídeos/genética , Placa Aterosclerótica/genética , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Humanos , Lipídeos/química , Camundongos , Camundongos Knockout , Nanoestruturas/química , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia
2.
Lab Anim ; 55(5): 472-477, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33884898

RESUMO

Breast cancer is the most common cancer among women worldwide. For high-risk women, contrast enhanced (CE)-magnetic resonance imaging (MRI) is recommended as supplemental screening together with mammography. The development of new MRI contrast agents is an active field of research, which requires efficacy tests on appropriate preclinical pathological models. In this work, a refined method to orthotopically induce breast cancer in BALB/c mice was developed using ultrasound (US) as a guide for the precise localisation of the tumour induction site and to improve animal welfare. The method was coupled with CE-MRI to characterise the evolution of the tumoural lesion.


Assuntos
Mamografia , Neoplasias , Animais , Meios de Contraste , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C , Ultrassonografia de Intervenção
3.
Oncotarget ; 11(24): 2310-2326, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32595830

RESUMO

Tumor-targeting contrast agents may facilitate resection of solid neoplasms during fluorescence-guided surgery. Preliminary safety and imaging efficacy of the near-infrared fluorescent probe DA364 were evaluated during surgical resection of spontaneous solid tumors in 24 dogs. Intra-operative imaging was performed in situ and on excised specimens to evaluate fluorescence intensities of tumor and adjacent tissues. After standard-of-care tumor resection, the wound bed was imaged again, and additional tissue was excised if residual fluorescence was detected. DA364 was well tolerated after intravenous administration. The median tumor-to-background ratio in situ for mammary tumors, mast cell tumors and sarcomas was 1.8 (range 1.2-3.9), 2.2 (range 1.0-5.6), and 4.2 (range 2.0-4.3), respectively. Qualitative intra-operative tumor identification was feasible in half of the cases. Remaining fluorescence was detected in four wound beds that contained residual disease, and in11 tumor-free wound beds, confirmed by histopathology. Overall, DA364 did not raise safety concerns and showed accumulation in different types of spontaneous tumors, showing potential to pinpoint residual disease. Larger clinical trials are necessary to select accurate dosing and imaging protocols for specific indications to evaluate the sensitivity and specificity of the agent.

4.
Animal Model Exp Med ; 2(1): 58-63, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31016288

RESUMO

Meningioma in vivo research is hampered by the difficulty of establishing an easy and reproducible orthotopic model able to mimic the characteristics of a human meningioma. Moreover, leptomeningeal dissemination and high mortality are often associated with such orthotopical models, making them useless for clinical translation studies. An optimized method for inducing meningiomas in nude mice at two different sites is described in this paper and the high reproducibility and low mortality of the models are demonstrated. Skull base meningiomas were induced in the auditory meatus and convexity meningiomas were induced on the brain surface of 23 and 24 nude mice, respectively. Both models led to the development of a mass easily observable by imaging methods. Dynamic contrast enhanced MRI was used as a tool to monitor and characterize the pathology onset and progression. At the end of the study, histology was performed to confirm the neoplastic origin of the diseased mass.

5.
Photoacoustics ; 11: 36-45, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30105205

RESUMO

PhotoAcoustic Imaging (PAI) is a biomedical imaging modality currently under evaluation in preclinical and clinical settings. In this work, ICG is coupled to an integrin binding vector (ICG-RGD) to combine the good photoacoustic properties of ICG and the favourable αvß3-binding capabilities of a small RGD cyclic peptidomimetic. ICG-RGD is characterized in terms of physicochemical properties, biodistribution and imaging performance. Tumor uptake was assessed in subcutaneous xenograft mouse models of human glioblastoma (U-87MG, high αvß3 expression) and epidermoid carcinoma (A431, low αvß3 expression). ICG and ICG-RGD showed high PA signal in tumors already after 15 min post-injection. At later time points the signal of ICG rapidly decreased, while ICG-RGD showed sustained uptake in U-87MG but not in A431 tumors, likely due to the integrin-mediated retention of the probe. In conclusion, ICG-RGD is a novel targeted contrast agents for PAI with superior biodistribution, tumor uptake properties and diagnostic value compared to ICG.

6.
J Med Chem ; 56(6): 2676-89, 2013 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-23458498

RESUMO

New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by Ki for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the (18)F-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding Bmax/Kd = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of (18)F-labeled MMP inhibitors was about 30% that of [(18)F]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin.


Assuntos
Radioisótopos de Flúor , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Metaloproteinases da Matriz/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Sulfonas/química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Técnicas de Química Sintética , Humanos , Camundongos , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , Traçadores Radioativos , Radioquímica , Albumina Sérica/metabolismo , Sulfonas/metabolismo , Sulfonas/farmacologia
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