Abstract: In the present work, the radioimmunoconjugates 111In-DTPA-trastuzumab and 177Lu-DOTA-trastuzumab were evaluated regarding the influence of the chelating agents on the physical–chemical parameters and human epidermal growth factor receptor 2 (HER2) tumor cell binding. Data showed that both chelating agents, at predetermined molar ratios (antibody:chelator 􀀀 1:10 and 1:20), did not influence the immunoconjugates integrity, the radiolabeling process and the radiolabeled antibodies stability. However, differences were observed in the lipophilic feature between DOTA and DTPA radioimmunoconjugates and in the specific binding to SK-BR-3 tumor cells (HER2 positive). Therefore, this study showed the importance of assessing the influence of chelating agents and their molar ratios in the development process of radioimmunoconjugates.

Palavras-Chave: tumor cells; neoplasms; drugs; therapeutic uses; radioimmunotherapy; chelating agents; radioisotopes

MIRANDA, ANA C.C.; DURANTE, ANA C.R.; FUSCALDI, LEONARDO L.; BARBEZAN, ANGELICA B.; LIMA, CILENE R. de; PERINI, EFRAIN; ARAUJO, ELAINE B. de. Anti-HER2 monoclonal antibody based-radioimmunoconjugates: assessment of the chelating agent influence. Bioorganic & Medicinal Chemistry, v. 33, p. 1-9, 2021. DOI: 10.1016/j.bmc.2021.115996. Disponível em: http://repositorio.ipen.br/handle/123456789/31971. Acesso em: $DATA.

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Abstract: Aim/Introduction: Few reports have documented the uptake of radiolabeled Prostate-Specific Membrane Antigen (PSMA) in lymphomas [1,2]. It is not known how PSMA uptake varies among various histological subtypes and how it correlates with 18F-FDG uptake in lymphomas. This study aimed to compare 68Ga-PSMA and 18F-FDG in different lymphoma subtypes. Materials and Methods: Nine randomly selected patients with biopsy-proven lymphoma -median age 43 (32-70) years, 5 female - were submitted to whole-body 18F-FDG and 68Ga- PSMA PET/CT (time interval: 1-6 days between procedures). Lymphoma subtypes included: nodular-sclerosis Hodgkin’s lymphoma (HL; 2 patients); diffuse large B-cell lymphoma (DLBCL; 1); marginal-zone lymphoma (2); MALT lymphoma (ML; 1); follicular lymphoma (FL; 1); lymphoplasmacytic lymphoma (1); and B-cell non- Hodgkin’s lymphoma, unspecified (BCNHL-U; 1). Eight patients were under initial staging, and 1 (HL) with disease relapse after treatment. Two experienced nuclear physicians analyzed the images by consensus. The intensity of tracer uptake was visually classified as marked, moderate or mild. The affected sites (lymph node chains, spleen, diffuse bone marrow involvement and non-lymphatic focal lesions) were counted in both sets of images and their respective maximum SUV (SUVmax) were measured. Results: PSMA PET/ CT was positive in all patients except for one with ML. FDG PET/CT was positive in all patients. At visual analyses, FDG uptake was higher than PSMA uptake in all patients, except for one patient with BCNHL-U (both tracers with similar low-intensity uptake). The intensity of FDG and PSMA uptake was respectively classified as marked in 3/9 and 0/8 patients, moderate in 4/9 and 1/8 and mild in 2/9 and 7/8. One patient (FL) presented a “mismatch” uptake pattern with different parts of an extensive lesion presenting predominant uptake of PSMA or FDG. Brain infiltration in one patient (DLBCL) was more easily identified on PSMA than on FDG images. FDG detected a total of 58/58 and PSMA 43/58 affected sites in all patients with a median SUVmax of respectively 5.4 (2.0-31.1) and 2.8 (1.3-5.4), p<0.0001. The median SUVs of the 43 lesions with uptake of both tracers was respectively 5.5 (2.0-28.9) and 2.8 (1.3-P5.4) for FDG and PSMA, p<0.0001. Conclusion: Distinct lymphoma subtypes present PSMA uptake, with less intensity than FDG uptake. Although PSMA uptake is usually mild, several lymphoma subtypes might cause false-positive results in PSMA PET/CT performed to assess prostate cancer.

RAMOS, C.; SOUZA, S.; TOBAR, N.; CASTRO, V.; FRASSON, F.; AMORIM, B.; ETCHEBEHERE, E.; LIMA, M.; MENGATTI, J.; ARAUJO, E.; PERINI, E.; SOUZA, C.; LORAND-METZE, I.; SANTOS, A.; DELAMAIN, M. Comparison of 68Ga-PSMA and 18F-FDG PET/CT uptake in different lymphoma subtypes: preliminary results. European Journal of Nuclear Medicine and Molecular Imaging, v. 47, p. S41-S42, 2020. Supplement 1, DOI: 10.1007/s00259-020-04988-4. Disponível em: http://repositorio.ipen.br/handle/123456789/32697. Acesso em: $DATA.

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Abstract: Purpose: A great challenge in the brachytherapy sources production is to fulfill the Good Manufacturing Practices (GMPs) requirements, involving the process validation and of all supporting activities such as cleaning and sanitization. The increasingly strict requirements for quality assurance system, with several norms, normative resolutions and rules that must follow both medical products and radiochemical requirements, has led to a constant validation concerns. The main goal of GMP is to reduce inherent risks such as product contamination with microorganisms and cross-contamination. Methods: In the Laboratory for Brachytherapy Sources Production it was established a cleaning program for cleanrooms and hot cells using a hydrogen peroxide solution (6%). This work aims to assess the effectiveness of this cleaning agent in reducing and/or eliminating microbial load into the cleanrooms and equipments to acceptable levels in accordance with the current legislation. Results: The analysis was conducted using the results of the environmental monitoring program with settling contact plates in cleanrooms after the cleaning procedures. Furthermore, it was possible to evaluate the action of the sanitizing agent on the microbial population at the equipment and cleanrooms’ surfaces. It was also evaluated the best way to accomplish the cleaning program considering the dosimetry factor in each production process, hence the importance of radiological contamination. All the following environmental monitoring procedures presented satisfactory results, showing that the cleaning procedures was able to reduce and maintain the acceptable levels of viable and non-viable particles for the cleanroom classification (ISO 5 and ISO 7). The cleaning process with this sanitizer (hydrogen peroxide) can be performed quickly right before the production; allowing the production of brachytherapy sources without after use residues. Conclusion: This data will help the production of a clean and reliable product.

Palavras-Chave: radiopharmaceutical; isotope production; cleaning; equipment; clean rooms; pollution sources; contamination; hydrogen peroxide

BAPTISTA, T.; ROSTELATO, M.C.M.; ZEITUNI, C.; PERINI, E.A.; SOUZA, C.D. de; MARQUES, J. de O.; NOGUEIRA, B.R.; ANGELOCCI, L.V. Efficiancy of hydrogen peroxide for cleaning production areas and equipments in the Laboratory for Brachyterapy Sources Production. Medical Physics, v. 44, n. 6, p. 2828-2828, 2017. DOI: 10.1002/mp.12304. Disponível em: http://repositorio.ipen.br/handle/123456789/31132. Acesso em: $DATA.

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Abstract: Pandemics reverberated their times, changing social and economic contexts, prompting, and redirecting changes in social ties, business, and education, restructuring the world that generated them. In this context, this study aims to assess the impact of the COVID-19 pandemic on the global energy matrix, supported by an analysis of consumption, demand, and GDP from January 2019 to June 2021. The energy balance showed variations in this period, with impacts on the environment. We will assess whether the changes will be lasting.

Palavras-Chave: coronaviruses; social impact; energy analysis; economic analysis; environment; energy consumption; electricity

FERRARI, L.A.; LIMA, L.M.P.R.; RODRIGUES, E.A.; PEREIRA, M.A.M.G.; LIMA, M.; PERINI, E.A.; AYOUB, J.M.S.; SENEDA, J.A. Energy and Covid 19: analysis of the impact on the global energy matrix. Brazilian Journal of Radiation Sciences, v. 10, n. 3A, p. 1-26, 2022. DOI: 10.15392/2319-0612.2022.1966. Disponível em: http://repositorio.ipen.br/handle/123456789/33487. Acesso em: $DATA.

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Abstract: Purpose: Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes. Methods: Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin’s lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin’s lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images. Results: FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0–8.2) to 30.9 for FDG and from 1.7 (1.7–1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images. Conclusion: HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas.

Palavras-Chave: diagnosis; neoplasms; prostate; antigens; gallium 68; lymphomas; hodgkins disease

SOUZA, STEPHAN P.M. de; TOBAR, NATALIA; FRASSON, FERNANDA; PERINI, EFRAIN A.; SOUZA, CARMINO A. de; DELAMAIN, MARCIA T.; RAMOS, CELSO D. Head-to-head comparison between 68Ga-PSMA and 18F-FDG-PET/CT in lymphomas: a preliminary analysis. Nuclear Medicine Communications, v. 42, n. 12, p. 1355-1360, 2021. DOI: 10.1097/MNM.0000000000001465. Disponível em: http://repositorio.ipen.br/handle/123456789/32810. Acesso em: $DATA.

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Abstract: Losartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT1Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT1R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, [18F]fluoroethyl-losartan ([18F]FEtLos) and [18F]ammoniomethyltrifluoroborate-losartan ([18F]AMBF3Los). [18F]FEtLos was radiolabeled by 18F-fluoroalkylation of losartan potassium using the prosthetic group 2-[18F]fluoroethyl tosylate; whereas [18F]AMBF3Los was prepared following an one-step 18F-19F isotopic exchange reaction, in an overall yield of 2.7 ± 0.9% and 11 ± 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT1R-expressing membranes showed that AMBF3Los presented an almost equivalent binding affinity (Ki 7.9 nM) as the cold reference Losartan (Ki 1.5 nM), unlike FEtLos (Ki 2000 nM). In vitro and in vivo assays showed that [18F]AMBF3Los displayed a good binding affinity for AT1R-overexpressing CHO cells and was able to specifically bind to renal AT1R. Hence, our data demonstrate [18F]AMBF3Los as a new tool for PET imaging of AT1R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases.

Palavras-Chave: drugs; cardiovascular diseases; angiotensin; in vitro; positron computed tomography; autoradiography

PIJEIRA, MARTHA S.O.; NUNES, PAULO S.G.; SANTOS, SOFIA N. dos; ZHANG, ZHENGXING; NARIO, ARIAN P.; PERINI, EFRAIN A.; TURATO, WALTER M.; RIERA, ZALUA R.; CHAMMAS, ROGER; ELSINGA, PHILIP H.; LIN, KUO-SHYAN; CARVALHO, IVONE; BERNARDES, EMERSON S. Synthesis and evaluation of [18F]FEtLos and [18F]AMBF3Los as novel 18F-labelled losartan derivatives for molecular imaging of angiotensin II type 1 receptors. Molecules, v. 25, n. 8, p. 1-21, 2020. DOI: 10.3390/molecules25081872. Disponível em: http://repositorio.ipen.br/handle/123456789/31407. Acesso em: $DATA.

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