Antimicrobial peptide for bacterial infection imaging: first case reported in Brazil.

Molecular imaging markers can be used to differentiate between infection and aseptic inflammation, determine the severity of infection, and monitor treatment responses. One of these markers is ubiquicidin(29-41) (UBI), a cationic peptide fragment that binds to the bacterial membrane wall and is labeled with gallium-68 (68Ga), a positron emitter radioisotope. The use of UBI in positron emission tomography (PET)/computed tomography (CT) for improved detection of lesions has been receiving considerable attention recently. Herein, we report the first case of 68Ga-UBI PET/CT performed in Brazil. The patient was a 39-year-old woman referred for a scan to confirm a clinical suspicion of chronic osteomyelitis of her fractured left tibia. PET images revealed radiotracer uptake near the posterior contour of the tibial fracture focus and the fixation plate, in the soft tissue around the distal half of the tibia, and in the non-consolidated fracture of the left distal fibula. Surgery for local cleaning was performed, and culture of a specimen collected from the surgical site confirmed the presence of Staphylococcus aureus. In the present case, 68Ga-UBI PET/CT, a non-invasive imaging modality, identified the infection foci in vivo, indicating its potential for clinical use.

Could 68 Ga-DOTA-UBI-29-41 Help Identify Chronic Osteomyelitis on PET/CT Images? A Pilot Study.

ABSTRACT: This pilot study aimed to confirm the presence of infectious agents in infection foci using PET/CT imaging with 68 Ga-DOTA-UBI (29-41) in 7 patients with chronic osteomyelitis and with indications for surgical cleaning at the site of the infection focus. The whole-body PET/CT was performed on Biograph mCT 40 PET/CT scanner (Siemens Healthineers); the image began 45-60 minutes postinjection of the radiotracer (148-260 MBq). This study demonstrated that, in 6 patients in whom the PET/CT was classified as positive for identified infectious foci, confirmed by culture of the secretion sample collected during surgery, only 1 patient in antibiotic therapy was negative.

Antimicrobial peptide for bacterial infection imaging: first case reported in Brazil

ABSTRACT Molecular imaging markers can be used to differentiate between infection and aseptic inflammation, determine the severity of infection, and monitor treatment responses. One of these markers is ubiquicidin(29-41) (UBI), a cationic peptide fragment that binds to the bacterial membrane wall and is labeled with gallium-68 (68Ga), a positron emitter radioisotope. The use of UBI in positron emission tomography (PET)/computed tomography (CT) for improved detection of lesions has been receiving considerable attention recently. Herein, we report the first case of 68Ga-UBI PET/CT performed in Brazil. The patient was a 39-year-old woman referred for a scan to confirm a clinical suspicion of chronic osteomyelitis of her fractured left tibia. PET images revealed radiotracer uptake near the posterior contour of the tibial fracture focus and the fixation plate, in the soft tissue around the distal half of the tibia, and in the non-consolidated fracture of the left distal fibula. Surgery for local cleaning was performed, and culture of a specimen collected from the surgical site confirmed the presence of Staphylococcus aureus. In the present case, 68Ga-UBI PET/CT, a non-invasive imaging modality, identified the infection foci in vivo, indicating its potential for clinical use.

Radiosynthesis Standardization and Preclinical Assessment of the [68Ga]Ga-DOTA-Ubiquicidin29-41: A Translational Study Targeting Differential Diagnosis of Infectious Processes.

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [68Ga]Ga-DOTA-Ubiquicidin29-41 was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (-3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in Staphylococcus aureus-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (p < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by Staphyloccocus aureus bacteria. These results indicate the potential of [68Ga]Ga-DOTA-Ubiquicidin29-41 as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT.

Evaluation of dopamine transporter density in healthy Brazilians using Tc-99m TRODAT-1 SPECT.

ABSTRACT: The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging.We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP.We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [R2] linear = 0.466) and left striatum (R2 linear = 0.510). Women presented a higher DAT-BP than men (women: R2 linear = 0.431; men: R2 linear = 0.457); nonetheless, their decrease by age group was equal to that in men.Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.

Virtual Rehabilitation in Parkinson Disease: A Dopamine Transporter Imaging Study.

OBJECTIVE: The aim of the study was to verify the effect of a virtual rehabilitation protocol for patients with Parkinson disease, primarily assessing striatal dopamine transporters and secondarily motor symptoms and quality of life. DESIGN: Nineteen patients with Parkinson disease underwent an 8-wk virtual rehabilitation protocol using XBOX 360S. Evaluation of dopamine transporters was performed by single-photon emission computed tomography using TRODAT-1 as the radioligand. Participants were clinically assessed using the Unified Parkinson Disease Rating Scale to quantify motor symptoms. Moreover, the Parkinson Disease Questionnaire and Short-Form Health Status Survey were used to assess quality of life and the Berg Balance Scale to assess balance. RESULTS: Regarding our primary outcome, dopamine transporter was significantly increased in the putamen contralateral to the clinically most affected body side (P = 0.034) considering preintervention and postintervention measurements. Furthermore, we observed significant improvement in Unified Parkinson Disease Rating Scale (10-point reduction, P = 0.001), Parkinson Disease Questionnaire (11.3-point reduction, P = 0.001), Short-Form Health Status Survey ("Functional capacity," P = 0.001; "Pain," P = 0.006; and "Mental Health" domains, P < 0.001), and Berg Balance Scale (5-point increase, P = 0.015). CONCLUSIONS: In our group of Parkinson disease patients, this virtual rehabilitation protocol enabled a dopamine transporter increase in the region of the putamen contralateral to the clinically most affected body side. Moreover, motor signs and quality of life were significantly improved.

PET/MRI: a novel hybrid imaging technique. Major clinical indications and preliminary experience in Brazil.

In recent years, medical imaging with hybrid techniques has widely accepted and employed in clinical routine. PET/MRI offers significant advantages, including excellent contrast and resolution and reduced ionizing radiation, as compared to well-established PET/CT. Therefore, PET/MRI is a promising modality for oncologic imaging of some regions, such as brain, head and neck, liver and pelvis. This article set out to analyze clinical conditions that could benefit from PET/MRI imaging based on our caseload. The potential of PET/MRI to become the imaging modality of choice for assessment of neurologic and oncologic conditions associated with soft tissues is highlighted. Clinical aspects of PET/MRI and its application to clinical cases are illustrated with examples extracted from the authors' preliminary experience. RESUMO Nos últimos anos, imagens médicas com tecnologias híbridas tornaram-se amplamente aceitas e utilizadas na prática clínica. O PET/RM possui vantagens importantes, incluindo excelentes contrastes e resolução, e menor radiação ionizante, em comparação ao PET/TC. Por isto, é uma modalidade promissora para exames de imagem de pacientes oncológicos, para avaliar o cérebro, cabeça e pescoço, o fígado e a pelve. O objetivo deste artigo foi analisar as situações clínicas que se beneficiariam de exames de PET/RM a partir de uma casuística. Destacamos o potencial desta técnica se tornar o método de imagem de escolha para doenças neurológicas e oncológicas que envolvam partes moles. Os aspectos clínicos de PET/RM e sua aplicação aos casos clínicos são ilustrados com exemplos da experiência inicial dos autores.

PET/MRI: a novel hybrid imaging technique. Major clinical indications and preliminary experience in Brazil / PET/RM: um novo método de imagem híbrida. Principais indicações clínicas e experiência preliminar no Brasil

ABSTRACT In recent years, medical imaging with hybrid techniques has widely accepted and employed in clinical routine. PET/MRI offers significant advantages, including excellent contrast and resolution and reduced ionizing radiation, as compared to well-established PET/CT. Therefore, PET/MRI is a promising modality for oncologic imaging of some regions, such as brain, head and neck, liver and pelvis. This article set out to analyze clinical conditions that could benefit from PET/MRI imaging based on our caseload. The potential of PET/MRI to become the imaging modality of choice for assessment of neurologic and oncologic conditions associated with soft tissues is highlighted. Clinical aspects of PET/MRI and its application to clinical cases are illustrated with examples extracted from the authors’ preliminary experience.

RESUMO Nos últimos anos, imagens médicas com tecnologias híbridas tornaram-se amplamente aceitas e utilizadas na prática clínica. O PET/RM possui vantagens importantes, incluindo excelentes contrastes e resolução, e menor radiação ionizante, em comparação ao PET/TC. Por isto, é uma modalidade promissora para exames de imagem de pacientes oncológicos, para avaliar o cérebro, cabeça e pescoço, o fígado e a pelve. O objetivo deste artigo foi analisar as situações clínicas que se beneficiariam de exames de PET/RM a partir de uma casuística. Destacamos o potencial desta técnica se tornar o método de imagem de escolha para doenças neurológicas e oncológicas que envolvam partes moles. Os aspectos clínicos de PET/RM e sua aplicação aos casos clínicos são ilustrados com exemplos da experiência inicial dos autores.

PET-CT as an Alternative to Fiducial Markers Guidance in Liver Metastasis Treatment.

The liver is the organ most commonly affected by colorectal cancer metastasis. Currently, liver resection is the treatment of choice, but in cases where it is not possible, intensity-modulated radiation therapy is an alternative. We report the case of a 57-year-old woman whose colorectal carcinoma metastasized to the liver. She was referred for implantation of fiducial markers for intensity-modulated radiation therapy planning. PET-CT stands out as an additional tool for distinguishing metabolically active tumor tissue from other tissues, ensuring effective introduction of percutaneous fiducial markers, especially in cases where use of conventional imaging techniques is limited.

99mTc-HYNIC-TOC increased uptake can mimic malignancy in the pancreas uncinate process at somatostatin receptor SPECT/CT.

OBJECTIVE: The aim of this study was to assess the occurrence and frequency of increased physiologic uptake of 99mTc-HYNIC-TOC by the uncinate process of the pancreas in SPECT/CT images. METHODS: Forty-six scans of 41 patients were evaluated retrospectively. The uptake of 99mTc-HYNIC-TOC was considered to be physiologic in patients with normal findings at dedicated abdominal CT or MR and lack of neoplastic lesions in clinical follow-ups. The intensity of uncinate process uptake was compared to the uptake of the normal liver. RESULTS: Focal uptake was attributed to the presence of pancreatic NET in 5 patients. Among the 36 patients without any evidence of malignancy in CT, MR and follow-up, 7 (19.4 %) showed increased uptake in the uncinate process. The intensity of uptake was lesser in 3 (8.3 %), similar in 3 and greater than the normal liver in 1 (2.8 %) case. CONCLUSION: Increased 99mTc-HYNIC-TOC uptake occurred in 19.4 % of those subjects without any evidence of neuroendocrine tumor in the uncinate process.

SPEM: a state-of-the-art instrument for high resolution molecular imaging of small animal organs.

OBJECTIVE: To describe the Single Photon Emission Microscope (SPEM), a state-of-the-art instrument for small animal SPECT imaging, and characterize its performance presenting typical images of different animal organs. METHODS: SPEM consists of two independent imaging devices based on high resolution scintillators, high sensitivity and resolution Electron-Multiplying CCDs and multi-pinhole collimators. During image acquisition, the mouse is placed in a rotational vertical holder between the imaging devices. Subsequently, an appropriate software tool based on the Maximum Likelihood algorithm iteratively produces the volumetric image. Radiopharmaceuticals for imaging kidneys, heart, thyroid and brain were used. The mice were injected with 74 to 148 MBq/0,3mL and scanned for 40 to 80 minutes, 30 to 60 minutes afterwards. During this procedure, the animals remained under ketamine/xilazine anesthesia. RESULTS: SPEM images of different mouse organs are presented, attesting the imaging capabilities of the instrument. CONCLUSION: SPEM is an innovative technology for small animal SPECT imaging providing high resolution images with appropriate sensitivity for pre-clinical research. Its use with appropriate radiotracers will allow translational investigation of several animal models of human diseases, their pharmacological treatment and the development of potential new therapeutic agents.

Estudo comparativo da qualidade de imagem dos modos de aquisição da PET: validação de um protocolo para reduzir a dose de radiação / Comparative study on imaging quality in PET acquisition modes: validation of a protocol for reducing the radiation dose

OBJETIVO: O presente experimento visa a validar um protocolo de aquisição em 3D na tomografia por emissão de pósitrons, em substituição ao modo 2D, de forma a reduzir a dose de radiação nos pacientes, sem perda da qualidade de imagens. MATERIAIS E MÉTODOS: Foram realizadas 27 simulações em equipamento Discovery ST, nos modos 2D com quatro minutos de aquisição e 3D com dois e quatro minutos. Utilizou-se um simulador do protocolo da National Electrical Manufacturers Association. No interior deste simulador estão inseridas seis esferas com diferentes diâmetros para a determinação da qualidade de imagem. As aquisições foram comparadas por três médicos nucleares, sem que eles identificassem o modo de aquisição. Cada observador atribuiu o valor igual a 1 quando alguma esfera não foi identificada ou valor 2 para esferas visíveis. RESULTADOS: A análise qualitativa pelo kappa generalizado demonstrou que a frequência de esferasvisíveis foi maior no modo 3D com quatro minutos (85%) e a porcentagem de concordância também foi maior (88,9%), com kappa generalizado = 0,725 [0,507;0,942]. CONCLUSÃO: O modo 3D com quatro minutos de aquisição e com menores atividades de FDG-18F pode ser utilizado em pacientes com biótipo equivalente ao simulador, sem perda de qualidade de imagem.

OBJECTIVE: The present study is aimed at validating a 3D acquisition protocol for positron emission tomography as a replacement for the 2D mode, to reduce the radiation dose delivered to patients, without any loss in the quality of images. MATERIALS AND METHODS: The study comprised 27 simulations in a Discovery ST equipment with four-minute 2D acquisitions, and two-minute and four-minute 3D acquisitions, utilizinga chest phantom according to the National Electrical Manufacturers Association protocol. Six spheres withdifferent diameters were inserted into this phantom as a means for determining the images quality. The images were blindly reviewed by three experienced nuclear physicians who did not know the acquisition modes. Each observer attributed a score 1 when one of the spheres was not identified, or 2 for visible spheres. RESULTS: The qualitative analysis based on generalized kappa coefficient demonstrated that the frequency of visible spheres was higher with four-minute 3D acquisitions (85%), with an also higher interobserver agreement (88.9%), generalized kappa = 0.725 [0.507;0.942]. CONCLUSION: The protocol with four-minute 3D acquisition with lower 18F-FDG activity can be utilized for patients with a biotype similar to the phantom, without any loss in the imaging quality.

Adaptação da técnica convencional de PET/CT para o planejamento radioterápico / Modification of conventional PET/CT technique for radiotherapy planning

A definição do volume a ser irradiado é o aspecto mais importante do planejamento radioterápico. As imagens de fusão da PET/CT permitem a visualização do tecido com aumento da atividade metabólica, o que melhora a delimitação do volume a ser tratado . A fim de reduzir os erros de fusão das imagens da PET com a TC, foram propostas algumas alterações do protocolo original que permitiram utilizar a PET/CT no planejamento radioterápico. No protocolo adaptado foi acrescentada, antes da aquisição da PET/CT, uma sequência tomográfica para visualização dos localizadores colocados no paciente durante a simulaçaõ do procedimento radioterápico e outra, logo após, com cortes mais finos, para reconstrução das imagens na estação de trabalho do planejamento radioterápico. De agosto/2004 a novembro/2005, foram realizados 88 planejamentos radioterápicos com auxílio das imagens da PET/CT. O alinhamento mecânico do eixo das duas modalidades permitiu a coincidência das imagens, reduzindo os erros de fusão em 99% dos casos, e possibilitou uma melhor avaliação da área de tratamento.

The definition of the tissue volume to be irradiated is the most important task in radiotherapy planning. A PET/CT fusion images allows the identification of the tissue with increased metabolic activity, thus enhancing the precise definition of the limits of the volume to be treated. To minimize errors that may occur by fusing the PET images with those of CT, some modifications were included to the original acquisition protocol which permitted the convenient utilization of PET/CT technique for the purposes of radiotherapy planning. The new protocol added one transmission tomographic sequence before conventional PET/CT, to check the position of the locators previously set for radiotherapy simulation, and a second multislice sequence after PET/CT for the purpose of reconstruction in the radiotherapy planning workstation. This second sequence is the one effectively used for the dosimetry plans. From August2004 through November 2005 88 radiotherapy plannings were performed at the PET/CT center according to the above described protocol. The mechanical axial alignment of the two imaging procedures thus achieved, resulted in near perfect image fusion in99% of the cases and improved the restriction of the treatment to the effective neoplasic tissue.

Experimental model in rat for sentinel node biopsy

Although sentinel node procedure has been used world wide, there are many aspects to be defined and better standardized. This study address if the experimental model in rats is appropriate for sentinel node biopsy. In this model, the lymph nodes are showed by lymphoscintigraphy, they are dyed by patent blue and identified by intraoperative gamma probe detection. It isnÆt necessary to use magnification for the procedure. The model demonstrated that sentinel node biopsy in rats is feasible. So, besides allowing researches in this field, the model is useful for training and diffusing this technique.