¹8F-Fluoride PET/CT is highly effective for excluding bone metastases even in patients with equivocal bone scintigraphy.

PURPOSE: Bone scintigraphy (BS) has been used extensively for many years for the diagnosis of bone metastases despite its low specificity and significant rate of equivocal lesions. (18)F-Fluoride PET/CT has been proven to have a high sensitivity and specificity in the detection of malignant bone lesions, but its effectiveness in patients with inconclusive lesions on BS is not well documented. This study evaluated the ability of (18)F-fluoride PET/CT to exclude bone metastases in patients with various malignant primary tumours and nonspecific findings on BS. METHODS: We prospectively studied 42 patients (34-88 years of age, 26 women) with different types of tumour. All patients had BS performed for staging or restaging purposes but with inconclusive findings. All patients underwent (18)F-fluoride PET/CT. All abnormalities identified on BS images were visually compared with their appearance on the PET/CT images. RESULTS: All the 96 inconclusive lesions found on BS images of the 42 patients were identified on PET/CT images. (18)F-Fluoride PET/CT correctly excluded bone metastases in 23 patients (68 lesions). Of 19 patients (28 lesions) classified by PET/CT as having metastases, 3 (5 lesions) were finally classified as free of bone metastases on follow-up. The sensitivity, specificity, and positive and negative predictive values of (18)F-fluoride PET/CT were, respectively, 100 %, 88 %, 84 % and 100 % for the identification of patients with metastases (patient analysis) and 100 %, 82 % and 100 % for the identification of metastatic lesions (lesion analysis). CONCLUSION: The factors that make BS inconclusive do not affect (18)F-fluoride PET/CT which shows a high sensitivity and negative predictive value for excluding bone metastases even in patients with inconclusive conventional BS.

Effect of thyroid-stimulating hormone in 68Ga-DOTATATE PET/CT of radioiodine-refractory thyroid carcinoma: a pilot study.

BACKGROUND: Radioiodine-refractory thyroid carcinomas (RAIRs) are characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin levels, and negative whole-body radioiodine scans. Interestingly, RAIRs continue to express somatostatin receptors and can be identified with Ga-DOTATATE PET/CT imaging. OBJECTIVE: The objective of this study was to compare lesion detectability in Ga-DOTATATE PET/CT performed with elevated thyroid-stimulating hormone (eTSH) levels with suppressed thyroid-stimulating hormone (sTSH) levels. PATIENTS AND METHODS: Fifteen patients with RAIR were prospectively enrolled in this pilot study. All patients underwent two Ga-DOTATATE PET/CT studies: with sTSH and with eTSH (after 30 days of levothyroxine withdrawal). All studies were blindly evaluated for differences pertaining to maximum standardized uptake values, detection of local recurrence, cervical lymph node (LN) metastases, cervical levels involved, distant LN metastases, lung metastases, and bone metastases. Reference standard consisted of fluorine-18-fluorodeoxyglucose PET/CT imaging, neck ultrasound, biopsy, and follow-up. RESULTS: Ga-DOTATATE PET/CT performed with both sTSH or eTSH was highly sensitive (91-100%) for detecting RAIR metastases. Ga-DOTATATE PET/CT with eTSH detected a higher total number of lesions (P=0.002), higher rate of cervical and distant LN metastases (P=0.002 and 0.0313, respectively), and significantly higher maximum standardized uptake values for cervical and distant LN metastases (P=0.0010 and 0.0078, respectively) when compared with sTSH. CONCLUSION: Ga-DOTATATE PET/CT presents a high sensitivity in detecting metastatic lesions in patients with RAIR. Detectability increases with iodine-resistance, both with and without higher thyroid-stimulating hormone levels. These findings might improve staging and subsequent treatment planning, especially with radiolabeled somatostatin analogs.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

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.

OBJETIVO: Avaliar o estudo SPECT/CT com análogos de somatostatina radiomarcados (RSA) em infecções granulomatosas sistêmicas, em comparação com o estudo com gálio-67 (67Ga). MATERIAIS E MÉTODOS: Vinte e oito paciente com infecção granulomatosa sistêmica ativa foram estudados, incluindo tuberculose, paracoccidioidomicose, pneumocistose, criptococose, aspergilose, leishmaniose, vasculite infecciosa e uma infecção oportunista inespecífica. Vinte e três tinham iniciado o tratamento previamente ao estudo. Todos fizeram imagem de varredura e SPECT/CT, 7 deles pós-injeção de 99mTc-EDDA-HYNIC-TOC e os outros 21 pós-injeção de 111In-DTPA-octreotide. Todos os pacientes também fizeram cintilografia com 67Ga, exceto um, que fez biópsia guiada por 99mTc-EDDA-HYNIC-TOC. RESULTADOS: Vinte e sete sítios de atividade foram detectados com 67Ga em 20 de 27 pacientes, também vistos nos estudos com RSA. Ambos foram negativos nos outros 7 pacientes. A captação de RSA foi visualmente menor que a de 67Ga em 11 de 20 pacientes positivos e similar nos outros 9. Um paciente que não pôde fazer cintilografia com 67Ga, fez biópsia guiada por 99mTc-EDDAHYNIC-TOC SPECT/CT em uma cavidade pulmonar com captação desse traçador, que foi positiva para aspergilose. CONCLUSÃO: SPECT/CT com 99mTc-EDDA-HYNIC-TOC ou 111In-DTPA-octreotide parece ser uma boa alternativa para o estudo com 67Ga na avaliação de pacientes com doença granulomatosa sistêmica.

Evaluation and comparison of a new DOTA and DTPA-bombesin agonist in vitro and in vivo in low and high GRPR expressing prostate and breast tumor models.

We evaluated and compared a new bombesin analog [Tyr-Gly5, Nle(14)]-BBN(6-14) conjugated to DOTA or DTPA and radiolabeled with In-111 in low and high GRPR expressing tumor models. Both peptides were radiolabeled with high radiochemical purity and specific activity. In vitro assays on T-47D, LNCaP and PC-3 cells showed that the affinity of peptides is similar and a higher binding and internalization of DOTA-peptide to PC-3 cells was observed. Both peptides could target PC-3 and LNCaP tumors in vivo and both tumor types could be visualized by microSPECT/CT.

Development of radioimmunoconjugate for diagnosis and management of head-and-neck subclinical cancer and colorectal carcinoma

ABSTRACT 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.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections / SPECT/CT com análogos radiomarcados de somatostatina na avaliação de infecções granulomatosas sistêmicas

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.

Resumo Objetivo: Avaliar o estudo SPECT/CT com análogos de somatostatina radiomarcados (RSA) em infecções granulomatosas sistêmicas, em comparação com o estudo com gálio-67 (67Ga). Materiais e Métodos: Vinte e oito paciente com infecção granulomatosa sistêmica ativa foram estudados, incluindo tuberculose, paracoccidioidomicose, pneumocistose, criptococose, aspergilose, leishmaniose, vasculite infecciosa e uma infecção oportunista inespecífica. Vinte e três tinham iniciado o tratamento previamente ao estudo. Todos fizeram imagem de varredura e SPECT/CT, 7 deles pós-injeção de 99mTc-EDDA-HYNIC-TOC e os outros 21 pós-injeção de 111In-DTPA-octreotide. Todos os pacientes também fizeram cintilografia com 67Ga, exceto um, que fez biópsia guiada por 99mTc-EDDA-HYNIC-TOC. Resultados: Vinte e sete sítios de atividade foram detectados com 67Ga em 20 de 27 pacientes, também vistos nos estudos com RSA. Ambos foram negativos nos outros 7 pacientes. A captação de RSA foi visualmente menor que a de 67Ga em 11 de 20 pacientes positivos e similar nos outros 9. Um paciente que não pôde fazer cintilografia com 67Ga, fez biópsia guiada por 99mTc-EDDAHYNIC-TOC SPECT/CT em uma cavidade pulmonar com captação desse traçador, que foi positiva para aspergilose. Conclusão: SPECT/CT com 99mTc-EDDA-HYNIC-TOC ou 111In-DTPA-octreotide parece ser uma boa alternativa para o estudo com 67Ga na avaliação de pacientes com doença granulomatosa sistêmica.

Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells.

OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 %. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 %ID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.

Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells

OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 percent) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 percent. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 percentID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 percent during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.

Garantia da qualidade aplicada à produção de radiofármacos: [revisão] / Quality assurance in radiopharmaceutical production: [review]

Radiofármacos são produzidos e distribuídos no Brasil há mais de 40 anos pelos Institutos da Comissão Nacional de Energia Nuclear (CNEN), particularmente o Instituto de Pesquisas Energéticas e Nucleares (IPEN), para uso em procedimentos diagnósticos e terapêuticos em Medicina Nuclear. Alguns aspectos da produção, distribuição e utilização dos radiofármacos são bastante particulares, diferenciando-se dos fármacos convencionais, tornando necessário estabelecer regulamentação específica para tais produtos. Neste sentido, existem orientações da Organização Mundial de Saúde (OMS) bem como regulamentações de órgãos sanitários de diversos países que já fazem distinção aos radiofármacos nas legislações específicas.

Radiopharmaceuticals have been produced and distributed in Brazil for almost 40 years, by the Institutes of the Comissão Nacional de Energia Nuclear (CNEN) particularly the Instituto de Pesquisas Energéticas e Nucleares (IPEN), and applied in Nuclear Medicine in diagnostic and therapeutic procedures. Some aspects related to the production, distribution and use of radiopharmaceuticals are very uncommon and different from the conventional drugs, making necessary the introduction of an specific regulation for these radioactive drugs. In this way, the World Health Organization (WHO) and health regulatory agencies from different countries have specific legislations to radiopharmaceuticals production and use.

Estudo para preparaçäo de tálio-201 no IPEN-CNEN/SP / Study for the preparation of tallium-201 in IPEN-CNEN/SP

O 201T1 foi obtido em ciclotron pela irradiaçäo de alvos naturais de mercúrio e tálio com prótons. Fêz-se um estudo destes métodos de preparaçäo de tálio-201, desde o preparo dos alvos, as técnicas de separaçäo química, até os controles de qualidade da soluçäo final de 201T1C1 e os experimentos para recuperaçäo de tálio. Os resultados apresentados em ambos os métodos nos levam a concluir da impossibilidade de se produzir o 201T1 no IPEN pelo custo do elemento enriquecido (no caso do alvo de mercúrio) e pela energia máxima de prótons do ciclotron modelo CV-28, instalado no IPEN, que é inadequada mesmo se utilizado alvo de tálio enriquecido