ADRIANA VIDAL FERNANDES MASSICANO

ADRIANA VIDAL FERNANDES MASSICANO

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Avaliação pré-clínica do potencial de inibidor do antígeno de membrana prostático específico (PSMA) radiomarcado com lutécio-177 no tratamento do câncer de próstata
2018 - SILVA, JEFFERSON de J.; MASSICANO, ADRIANA V.F.; ALCARDE, LAIS F.; BENEDETTO, RAQUEL; BOAS, CRISTIAN A.W.V.; DIAS, LUIS A.P.; MENGATTI, JAIR; ARAUJO, ELAINE B. de
Diversos radiofármacos PSMA-específicos têm sido apresentados como proposta para o diagnóstico do câncer de próstata, bem como para o tratamento de pacientes com câncer metastático resistente à castração e às terapias convencionais. Este trabalho estudou a marcação e estabilidade radioquímica do inibidor do receptor PSMA, Glu-NH-CO-NH-Lys(Ahx)-DOTA com 177Lu (PSMA-DOTA-177Lu), e realizou estudos pré-clínicos para avaliar seu potencial para a terapia do câncer de próstata. O radiofármaco foi obtido com pureza radioquímica elevada (PR > 95%) em todas as condições de marcações estudadas e permaneceu estável quando armazenado sob congelamento por até 48 horas, mesmo com atividade específica alta (74 MBq/μg). O ensaio de ligação específica do PSMA-DOTA-177Lu mostrou fração significativa de ligação às células LNCaP de tumor de próstata, exclusivamente à superfície celular. Os parâmetros farmacocinéticos determinados no estudo in vivo em camundongos BALB/c são compatíveis com o rápido clareamento sanguíneo e excreção renal. O radiofármaco demonstrou alta estabilidade em soro humano in vivo por um período de até 24 horas, que foi confirmada pela baixa captação óssea demonstrada nos estudos in vivo de biodistribuição. Os resultados favoráveis deste estudo sugerem a realização de ensaio clínico controlado deste novo radiofármaco para avaliar seu potencial no tratamento do câncer de próstata.
Development of radioimmunoconjugate for diagnosis and management of head-and-neck subclinical cancer and colorectal carcinoma
2018 - BENEDETTO, RAQUEL; MASSICANO, ADRIANA V.F.; SILVA, JEFFERSON J.; BOAS, CRISTIAN A.W.V.; MENGATTI, JAIR; ARAUJO, ELAINE B. de
Scientific innovations in diagnostic methods are important drivers of cancer control and prevention. Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous, cell carcinoma and colorectal cancer could be valuable to select patients for EGFR-targeted therapy, as well as to monitor the efficacy and occurrence of resistance to immunotherapy. In order to develop the first Brazilian radioimmunoconjugate for diagnosis, Cetuximab has been conjugated to p-SCN-Bn-DTPA chelator and radiolabeled with Indium-111. The conjugation methodology was optimized using different mAb:DTPA molar ratios, time was then reduced for immunoconjugate preparation, besides the protein recovery’ percentage increased after purification (m = 83.8 ± 0.91 %). The stability of Cetuximab-DTPA at – 20 oC was evaluated for six months, and its integrity was greater than 90% (m =93.9 ± 1.5%, N = 24). The radioimmunoconjugate with specific activity of 185 MBq/mg showed radiochemical purity above 95% (m=96.8 ± 1.31 %, N = 15). We conclude that the radioimmunoconjugate 111In-DTPA-cetuximab is stable and may be applied to the diagnosis of EGFR-positive tumors.
Development and biological studies of sup(177)Lu-DOTA-rituximab for the treatment of non-hodgkin's lymphoma
2016 - MASSICANO, ADRIANA V.F.; PUJATTI, PRISCILLA B.; ALCARDE, LAIS F.; SUZUKI, MIRIAM F.; SPENCER, PATRICK J.; ARAUJO, ELAINE B.
The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.
Development of a new bombesin analog radiolabelled with lutetium-177
2010 - PUJATTI, P.B.; SANTOS, J.S.; MASSICANO, A.V.F.; MENGATTI, J.; ARAUJO, E.B. de
In this work we describe the first results of radiolabeling with lutetium-177 (177Lu) and in vivo biodistribution and pharmacokinetics studies in normal Balb-c mice of a new bombesin analog (BEFG2) – DOTA-Phe-X-BBN(6-14), where X is a spacer of two aminoacids. Bombesin (BBN) is an amphibian analog of human gastrin releasing peptide (GRP). Development of radiolabeled BBN derivatives as agents for diagnostic imaging and systemic radiotherapy has increased considerable because of the observation that GRP receptors (GRPr) are over-expressed in a variety of human tumor cells, such as prostate tumor cells. 177Lu-labeled peptides are attractive due to the excellent radiophysical properties and commercial availability of the radiometal. BEFG2 was successfully labeled with high yield and kept stable for more than 96 hours at 2-8º C and 1 hour in human plasma. Data analysis obtained from the in vivo studies showed that the amount of BEFG2 present in plasma decreased rapidly and became almost undetectable at 60 min p.i., indicating rapid peptide excretion, which is performed mainly by renal pathway. In addition, biodistribution and single photon emission tomography showed low abdominal accumulation of 177Lu-DOTA- Phe-X-BBN(6-14), indicating that this analog is a potential candidate for tumors target therapy.
A portable test system for determination of bacterial endotoxins in sup(18)F-FDG, sup(99m)Tc, and lyophilized reagents for labeling with sup(99m)Tc
2011 - FUKUMORI, NEUZA T.O.; CAMPOS, DOMINGOS G. de; MASSICANO, ADRIANA V.F.; PEREIRA, NILDA P.S. de; SILVA, CONSTANCIA P.G. da; MATSUDA, MARGARETH M.N.
Preparation of [In-111]-labeled-DTPA-bombesin conjugates at high specific activity and stability: evaluation of labeling parameters and potential stabilizers
2012 - PUJATTI, P.B.; MASSICANO, A.V.F.; MENGATTI, J.; ARAUJO, E.B. de