Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease.

OBJECTIVE: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. METHODS: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. RESULTS: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. CONCLUSIONS: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Correction to: Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

In the last paragraph of the subsession "Recruitment of the study population and clinical Evaluation" (Material and methods session).

Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

PURPOSE: [18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches." METHODS: Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics. RESULTS: AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES). CONCLUSION: The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

SUV Normalized by Skeletal Volume on 18F-Fluoride PET/CT Studies.

OBJECTIVE: To propose a technique for SUV normalization on F-fluoride PET/CT (F-NaF) studies based on skeletal volume and to compare the SUVs normalized by this technique with the ones normalized by body weight. METHODS: SUVs were obtained in volumes of interest (VOIs) in proximal diaphyseal regions of the right humerus (HD) and right femur (FD) in 12 selected F-NaF studies. The 12 studies presented both regions considered normal by visual examination on PET and CT and were performed in patients presenting body weight below 50 kg (B50) or above 90 kg (A90) (6 patients in each group). The maximum SUVs were calculated in these 2 bone regions in both groups of patients using body weight (SUV BW) and skeletal volume (SUV SV) methodologies. The total skeletal volume for each patient was estimated based on whole skeletal VOIs automatically defined on the CT component of the PET/CT study. The maximum SUVs calculated using the 2 methodologies were compared. RESULTS: The maximum SUVs BW were statistically higher in the group A90 in both regions, with a P < 0.001 and P < 0.008 for FD and HD, respectively. The maximum SUVs SV in the 2 regions were not statistically different between the groups B50 and A90, P values of 0.27 and 0.87 for FD and HD, respectively. CONCLUSIONS: The SUVs normalized by skeletal volume present similar results in groups of patients with extremes of body weight. Therefore, this methodology could be more adequate than the one normalized by body weight to semiquantitatively analyze F-NaF studies.

Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models.

Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 ± 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 ± 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.

Dose calibrator linearity test: (99m)Tc versus (18)F radioisotopes.

OBJECTIVE: The present study was aimed at evaluating the viability of replacing (18)F with (99m)Tc in dose calibrator linearity testing. MATERIALS AND METHODS: The test was performed with sources of (99m)Tc (62 GBq) and (18)F (12 GBq) whose activities were measured up to values lower than 1 MBq. Ratios and deviations between experimental and theoretical (99m)Tc and (18)F sources activities were calculated and subsequently compared. RESULTS: Mean deviations between experimental and theoretical (99m)Tc and (18)F sources activities were 0.56 (± 1.79)% and 0.92 (± 1.19)%, respectively. The mean ratio between activities indicated by the device for the (99m)Tc source as measured with the equipment pre-calibrated to measure (99m)Tc and (18)F was 3.42 (± 0.06), and for the (18)F source this ratio was 3.39 (± 0.05), values considered constant over the measurement time. CONCLUSION: The results of the linearity test using (99m)Tc were compatible with those obtained with the (18)F source, indicating the viability of utilizing both radioisotopes in dose calibrator linearity testing. Such information in association with the high potential of radiation exposure and costs involved in (18)F acquisition suggest (99m)Tc as the element of choice to perform dose calibrator linearity tests in centers that use (18)F, without any detriment to the procedure as well as to the quality of the nuclear medicine service.

OBJETIVO: Avaliar a viabilidade de substituir o radioisótopo 18F pelo 99mTc no teste de linearidade em medidores de atividade. MATERIAIS E MÉTODOS: O teste foi realizado empregando-se fontes de 99mTc (62 GBq) e 18F (12 GBq), cujas atividades foram mensuradas até valores abaixo de 1 MBq. As razões e desvios entre as atividades experimentais e teóricas foram calculados e comparados. RESULTADOS: Os desvios médios entre as atividades experimentais e teóricas para o 99mTc e 18F foram, respectivamente, 0,56 (± 1,79)% e 0,92 (± 1,19)%. A razão média entre as atividades indicadas pelo equipamento para a fonte de 99mTc quando mensurada no equipamento pré-ajustado para medir o 99mTc e 18F foi 3,42 (± 0,06), e para o 18F este valor foi 3,39 (± 0,05), razões consideradas constantes ao longo de todo o período de medida. CONCLUSÃO: Os resultados do teste utilizando o 99mTc são compatíveis com os adquiridos com o 18F, implicando na possibilidade de utilização de ambos os radioisótopos na realização do teste de linearidade. Esta informação, aliada ao elevado potencial de exposição e custos de aquisição do 18F, sugere que o 99mTc seja empregado na realização do teste de linearidade para clínicas que utilizam 18F, sem prejuízo para o procedimento e garantia da qualidade de um serviço de medicina nuclear.

Dose calibrator linearity test: 99mTc versus 18F radioisotopes / Teste de linearidade em medidor de atividade: utilização do radioisótopo 99mTc versus 18F

Objective: The present study was aimed at evaluating the viability of replacing 18F with 99mTc in dose calibrator linearity testing. Materials and Methods: The test was performed with sources of 99mTc (62 GBq) and 18F (12 GBq) whose activities were measured up to values lower than 1 MBq. Ratios and deviations between experimental and theoretical 99mTc and 18F sources activities were calculated and subsequently compared. Results: Mean deviations between experimental and theoretical 99mTc and 18F sources activities were 0.56 (± 1.79)% and 0.92 (± 1.19)%, respectively. The mean ratio between activities indicated by the device for the 99mTc source as measured with the equipment pre-calibrated to measure 99mTc and 18F was 3.42 (± 0.06), and for the 18F source this ratio was 3.39 (± 0.05), values considered constant over the measurement time. Conclusion: The results of the linearity test using 99mTc were compatible with those obtained with the 18F source, indicating the viability of utilizing both radioisotopes in dose calibrator linearity testing. Such information in association with the high potential of radiation exposure and costs involved in 18F acquisition suggest 99mTc as the element of choice to perform dose calibrator linearity tests in centers that use 18F, without any detriment to the procedure as well as to the quality of the nuclear medicine service. .

Objetivo: Avaliar a viabilidade de substituir o radioisótopo 18F pelo 99mTc no teste de linearidade em medidores de atividade. Materiais e Métodos: O teste foi realizado empregando-se fontes de 99mTc (62 GBq) e 18F (12 GBq), cujas atividades foram mensuradas até valores abaixo de 1 MBq. As razões e desvios entre as atividades experimentais e teóricas foram calculados e comparados. Resultados: Os desvios médios entre as atividades experimentais e teóricas para o 99mTc e 18F foram, respectivamente, 0,56 (± 1,79)% e 0,92 (± 1,19)%. A razão média entre as atividades indicadas pelo equipamento para a fonte de 99mTc quando mensurada no equipamento pré-ajustado para medir o 99mTc e 18F foi 3,42 (± 0,06), e para o 18F este valor foi 3,39 (± 0,05), razões consideradas constantes ao longo de todo o período de medida. Conclusão: Os resultados do teste utilizando o 99mTc são compatíveis com os adquiridos com o 18F, implicando na possibilidade de utilização de ambos os radioisótopos na realização do teste de linearidade. Esta informação, aliada ao elevado potencial de exposição e custos de aquisição do 18F, sugere que o 99mTc seja empregado na realização do teste de linearidade para clínicas que utilizam 18F, sem prejuízo para o procedimento e garantia da qualidade de um serviço de medicina nuclear. .

Effect of intertrochanteric osteotomy on the proximal femur of rabbits: assessment with power Doppler sonography and scintigraphy.

OBJECTIVE: In bone injury, repair results in local increased vascularity and bone marrow remodeling. Characterizing the vascular and metabolic imaging patterns of the proximal femur following an intertrochanteric osteotomy may help clinicians decide proper management of the patient. Our objective was to measure Doppler sonography and scintigraphy interval changes in the proximal femur following intertrochanteric osteotomy and compare imaging and histomorphometric measurements in the late post-operative stage (6 weeks after surgery) in a rabbit model of bone injury. MATERIALS AND METHODS: Both hips of 12 adult rabbits were imaged with power Doppler sonography and scintigraphy prior to and after (7 days and 6 weeks) unilateral osteotomy. Accuracy of the imaging methods was evaluated using hip operative status and histomorphometric results (vascular fractional area and number of vessels per area unit) as reference standard measures. RESULTS: A significant difference in the mean number of pixels was noted between operated and non-operated femura in late post-operative power Doppler examinations (P=0.049). Although without reaching statistical significance, the AUC of Doppler measurements (AUC=0.99) was numerically greater than the AUC of scintigraphy measurements (AUC=0.857+/-0.099) (P=0.15) in differentiating proximal femura with regard to their fractional vascular areas in the late post-operative stage. In contrast, scintigraphy tended to perform better (AUC=0.984+/-0.022) than Doppler ultrasound (AUC=0.746+/-0.131) to demonstrate the vascularity intensity per area unit (P=0.07) in the late stage. CONCLUSION: Our results warrant further investigation to determine the value of different imaging modalities for assessment of pathologic changes following hip surgery. Power Doppler sonography demonstrated larger AUCs (representing higher accuracy) for the discrimination of vascular fractional areas and scintigraphy, for discrimination of the number of vessels per area unit.

Effect of intertrochanteric osteotomy on the proximal femur of rabbits: assessment with power Doppler sonography and scintigraphy

OBJECTIVE: In bone injury, repair results in local increased vascularity and bone marrow remodeling. Characterizing the vascular and metabolic imaging patterns of the proximal femur following an intertrochanteric osteotomy may help clinicians decide proper management of the patient. Our objective was to measure Doppler sonography and scintigraphy interval changes in the proximal femur following intertrochanteric osteotomy and compare imaging and histomorphometric measurements in the late post-operative stage (6 weeks after surgery) in a rabbit model of bone injury. MATERIALS AND METHODS: Both hips of 12 adult rabbits were imaged with power Doppler sonography and scintigraphy prior to and after (7 days and 6 weeks) unilateral osteotomy. Accuracy of the imaging methods was evaluated using hip operative status and histomorphometric results (vascular fractional area and number of vessels per area unit) as reference standard measures. RESULTS: A significant difference in the mean number of pixels was noted between operated and non-operated femura in late post-operative power Doppler examinations (P=0.049). Although without reaching statistical significance, the AUC of Doppler measurements (AUC=0.99) was numerically greater than the AUC of scintigraphy measurements (AUC=0.857±0.099) (P=0.15) in differentiating proximal femura with regard to their fractional vascular areas in the late post-operative stage. In contrast, scintigraphy tended to perform better (AUC=0.984±0.022) than Doppler ultrasound (AUC=0.746±0.131) to demonstrate the vascularity intensity per area unit (P=0.07) in the late stage. CONCLUSION: Our results warrant further investigation to determine the value of different imaging modalities for assessment of pathologic changes following hip surgery. Power Doppler sonography demonstrated larger AUCs (representing higher accuracy) for the discrimination of vascular fractional areas and scintigraphy, for discrimination...

OBJETIVO: Regeneração em casos de lesão óssea resulta em aumento da vascularização local e remodelamento da medula óssea adjacente. A caracterização imagenológica de padrões vasculares e metabólicos no fêmur proximal após uma osteotomia intertrocantérica pode auxiliar ortopedistas a decidirem qual a terapêutica mais apropriada. O objetivo deste estudo foi avaliar as alterações temporais observadas por ultra-sonografia Doppler e cintilografia no fêmur proximal após a realização de uma osteotomia intertrocantérica; e comparar achados imagenológicos e histomorfométricos no estágio pós-operatório tardio (6 semanas após a cirurgia) num modelo animal de lesão óssea. MATERIAIS AND MÉTODOS: Ambos os quadris de 12 coelhos adultos foram examinados por ultra-sonografia power Doppler e cintilografia antes e após (7 dias e 6 semanas) uma osteotomia unilateral. A acurácia dos métodos de imagem foi avaliada usando-se o status operatório dos quadris and os resultados histomorfométricos (área vascular fracional e número de vasos/unidade de área) como medidas de referência. RESULTADOS: Uma diferença significativa foi observada entre o número médio de pixels presentes no fêmur proximal operado e não-operado ao exame de power Doppler obtido no estágio pós-operatório tardio (P=0.049). Embora ser atingir significância estatística, a área abaixo da curva ("area-under-the-curve") dos exames de power Doppler (AUC=0.99) for numericamente superior à área abaixo da curva dos exames de cintilografia (AUC= 0.857±0.099) (P=0.15) para diferenciar fêmures proximais com relação a suas áreas vasculares fracionais no estágio pós-operatório tardio. Ao contrário, a cintilografia tendeu a apresentar uma "performance" diagnóstica superior (AUC=0.984±0.022) em relação ao Doppler (AUC=0.746±0.131) para demonstrar a quantidade de vasos por unidade de área (P=0.07) no estágio tardio. CONCLUSÃO: Nossos resultados despertam a importância de continuar-se investigando...

Padronizacão do método para cálculo da captacão renal absoluta do 99mTc-DMSA em criancas / Standardization of a method to calculate absolute renal uptake of 99mTc-DMSA in children

OBJETIVO: O trabalho teve por objetivo padronizar o método e estabelecer valores normais da captacão renal absoluta do99mTc-DMSA em criancas. MATERIAIS E MÉTODOS: Vinte e duas criancas (idade de 7 meses a 10 anos; média de 4,5 anos) sem doenca renal prévia foram submetidas a cintilografia renal estática com 99mTc-DMSA. Dezoito apresentavam ultra-sonografia, uretrocistografia miccional, "clearance" de creatinina e padrão visual da cintilografia renal estática normais. Quatro criancas foram excluídas por não terem completado ou por apresentarem reducão do "clearance" de creatinina. A captacão absoluta de DMSA (DMSA-Abs) foi calculada como a porcentagem da atividade administrada retida em cada rim após seis horas da administracão do radiofármaco. RESULTADOS: Os valores de DMSA-Abs foram de 21,8 por cento n 3,2 por cento para o rim direito e de 23,1 por cento n 3,3 por cento para o rim esquerdo. Os valores da captacão absoluta não mostraram correlacão com a idade dos pacientes estudados, apesar da tendência de aumento do "clearance" de creatinina com a idade. CONCLUSAO: A definicão de valores normais da DMSA-Abs permite o emprego deste parâmetro na avaliacão inicial e acompanhamento de doencas renais, principalmente em pacientes com acometimento bilateral ou com rim único (nos quais a funcão diferencial direita X esquerda tem valor limitado).