Abstract: Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 (67Ga) citrate scintigraphy. Materials and Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

Palavras-Chave: biomedical radiography; computerized tomography; gallium 67; patients; positron computed tomography; technetium 99; tuberculosis

MONTEIRO, PAULO H.S.; SOUZA, THIAGO F. de; MORETTI, MARIA L.; RESENDE, MARIANGELA R.; MENGATTI, JAIR; LIMA, MARIANA da C.L. de; SANTOS, ALLAN O.; RAMOS, CELSO D. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections. Radiologia Brasileira, v. 50, n. 6, p. 378-382, 2017. DOI: 10.1590/0100-3984.2016.0076. Disponível em: http://repositorio.ipen.br/handle/123456789/28520. 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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Abstract: Background: Tissue hypoxia is a pathological condition characterized by reducing oxygen supply. Hypoxia is a hallmark of tumor environment and is commonly observed in many solid tumors. Non-invasive imaging techniques like positron emission tomography (PET) are at the forefront of detecting and monitoring tissue hypoxia changes in vivo. Results: We have developed a novel 18F-labeled radiotracer for hypoxia PET imaging based on cytotoxic agent benznidazole. Radiotracer N-(4-[18F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)acetamide ([18F]FBNA) was synthesized through acylation chemistry with readily available 4-[18F]fluorobenzyl amine. Radiotracer [18F]FBNA was obtained in good radiochemical yields (47.4 ± 5.3%) and high radiochemical purity (> 95%). The total synthesis time was 100 min, including HPLC purification and the molar activity was greater than 40 GBq/µmol. Radiotracer [18F]FBNA was stable in saline and mouse serum for 6 h. [18F]FBNA partition coefficient (logP = 1.05) was found to be more lipophilic than [18F]EF-5 (logP = 0.75), [18F]FMISO (logP = 0.4) and [18F]FAZA (logP =  − 0.4). In vitro studies showed that [18F]FBNA accumulates in gastric cancer cell lines AGS and MKN45 under hypoxic conditions. Conclusions: Hence, [18F]FBNA represents a novel and easy-to-prepare PET radioligand for imaging hypoxia.

Palavras-Chave: anoxia; nitro compounds; imidazoles; acetamide; positron computed tomography; oxygen; radiopharmaceuticals

NARIO, ARIAN P.; WOODFIELD, JENILEE; SANTOS, SOFIA N. dos; BERGMAN, CODY; WUEST, MELINDA; ARAUJO, YASNIEL B.; LAPOLLI, ANDRE L.; WEST, FREDERICK G.; WUEST, FRANK; BERNARDES, EMERSON S. Synthesis of a 2‑nitroimidazole derivative N‑(4‑[18F]fluorobenzyl)‑2‑(2‑nitro‑1H‑imidazol‑1‑yl)‑acetamide ([18F]FBNA) as PET radiotracer for imaging tumor hypoxia. EJNMMI Radiopharmacy and Chemistry, v. 7, n. 1, p. 1-16, 2022. DOI: 10.1186/s41181-022-00165-0. Disponível em: http://repositorio.ipen.br/handle/123456789/33169. Acesso em: $DATA.

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Abstract: Gaining prominence in clinical practice, the 68Ga, positron emitter radionuclide easily obtained by 68Ge/68Ga generator elution, has shown potential and excellent quality on radiolabeling of peptide for use in positron emission tomography (PET), in particular urea-based inhibitor peptides, directed to the prostate-specific membrane receptor (PSMA). Previous studies with the PSMA linked to the chelator HBED-CC (PSMA-11) radiolabeled with 68Ga showed high contrast PET/CT images to evaluate recurrence and metastasis of prostate cancer, becoming an important imaging agent in the clinical routine. This work intended to evaluate the influence of the quality of the 68Ge/68Ga generator eluate in direct labelling of PSMA-11 with 68Ga, assisting in the development of kit for prompt radiolabeling. It was evaluated the 68GaCl3 eluate from 68Ge/68Ga non-GMP generator (manufacturer A) and 68Ge/68Ga GMP generator (manufacturer B), both commercially available. To evaluate the influence of the 68Ga eluate on radiochemical yield of the preparations, the radiochemical purity was determined by thin layer chromatography and HPLC. The radiolabeling with non-GMP generator eluate was made with and without preliminary purification of the 68 gallium chloride eluate, employing cationic purification columns. The results showed higher radiochemical yield with the 68GaCl3 eluate from the 68Ge/68Ga GMP generator, obtaining the radiolabeled product more easily and speed to clinical practice, without preliminary purification, as opposed to the use of non-GMP 68Ge/68Ga generator which required preliminary purification of the 68GaCl3 eluate to promote satisfactory radiochemical purity results.

Palavras-Chave: carcinomas; prostate; neoplasms; positron computed tomography; membrane proteins; gallium 68; germanium 68

VIVALDINI, B.F.; ARAUJO, E.B. The influence of generator eluate in radiolabeling PSMA-11 kit with 68Ga. Brazilian Journal of Radiation Sciences, v. 9, n. 1A, p. 1-9, 2021. DOI: 10.15392/bjrs.v9i1A.1541. Disponível em: http://repositorio.ipen.br/handle/123456789/32139. Acesso em: $DATA.

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Abstract: Background: Despite the improvement in clinical outcomes for head and neck squamous cell carcinoma (HNSCC) as the result of cetuximab, patients may present with or develop resistance that increases tumor recurrence rates and limits clinical efficacy. Therefore, identifying those patients who are or become resistant is essential to tailor the best therapeutic approach. Materials and Methods: Cetuximab was conjugated to p-NCS-Bz-DFO and labeled with 89Zr. The resistance model was developed by treating FaDu cells with cetuximab. Western blotting (WB) and specific binding assays were performed to evaluate epidermal growth factor receptor (EGFR) expression and 89Zr-DFO-cetuximab uptake in FaDu cetuximab-resistant (FCR) and FaDu cetuximab-sensitive (FCS) cells. Positron emission tomography imaging and biodistribution were conducted in NU/NU nude mice implanted with FCR or FCS cells. Results: Cetuximab was successfully radiolabeled with 89Zr (‡95%). Binding assays performed in FCR and FCS cells showed significantly lower 89Zr-DFO-cetuximab uptake in FCR ( p < 0.0001). WB suggests that the resistance mechanism is associated with EGFR downregulation ( p = 0.038). This result is in agreement with the low uptake of 89Zr-DFO-cetuximab in FCR cells. Tumor uptake of 89Zr-DFO-cetuximab in FCR was significantly lower than FCS tumors ( p = 0.0340). Conclusions: In this work, the authors showed that 89Zr-DFO-cetuximab is suitable for identification of EGFR downregulation in vitro and in vivo. This radiopharmaceutical may be useful for monitoring resistance in HNSCC patients during cetuximab therapy.

Palavras-Chave: zirconium 89; positron computed tomography; carcinomas; radiopharmaceuticals; therapy; chemotherapy; antibodies; reagents

BENEDETTO, RAQUEL; MASSICANO, ADRIANA V.F.; CRENSHAW, BRYANT K.; OLIVEIRA, RENATO; REIS, RUI M.; ARAUJO, ELAINE B.; LAPI, SUZANNE E. Zr-89-DFO-cetuximab as a molecular imaging agent to identify cetuximab resistance in head and neck squamous cell carcinoma. Cancer Biotherapy and Radiopharmaceuticals, v. 34, n. 5, p. 288-296, 2019. DOI: 10.1089/cbr.2018.2616. Disponível em: http://repositorio.ipen.br/handle/123456789/30058. Acesso em: $DATA.

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