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.

Musculoskeletal pitfalls in 68Ga-PSMA PET/CT.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in normal prostate cells and overexpressed in prostate cancer. Consequently, it is an important tool in the evaluation of prostate cancer, including the staging of high-risk patients and the assessment of biochemical recurrence. Despite the "specific" designation, benign musculoskeletal conditions, such as fractures, osteodegenerative changes, and fibrous dysplasia, can also show PSMA uptake, which can lead to misinterpretation of the imaging findings. Therefore, radiologists must be aware of these potential pitfalls, understand their causes, and fully analyze their morphologic features on unfused computed tomography (CT) and magnetic resonance imaging scans to correctly interpret the examination. In this pictorial essay, we review the basic characteristics of the 68Ga-PSMA positron-emission tomography/CT (PET/CT) radiotracer, discuss potential causes of false-positive findings on 68Ga-PSMA PET/CT in the musculoskeletal system, and illustrate the corresponding imaging findings.

O antígeno de membrana próstata específico (PSMA) é uma proteína transmembrana que apresenta expressão em células prostáticas normais e superexpressão em neoplasia da próstata. Dessa forma, é uma importante ferramenta na avaliação da neoplasia prostática, de utilidade no estadiamento de pacientes de alto risco e na análise de recorrência bioquímica. Apesar do termo "específico", condições musculoesqueléticas benignas podem demonstrar captação de PSMA, como fraturas, alterações osteodegenerativas e displasia fibrosa, podendo levar a uma avaliação equivocada dos achados de imagem. Assim, o radiologista deve conhecer esses potenciais pitfalls, compreender suas causas e analisar as características morfológicas nas imagens não fundidas de TC e RM para interpretar corretamente o exame. Neste ensaio iconográfico, revisaremos as características básicas do radiofármaco 68Ga-PSMA PET/CT, discutiremos possíveis causas de resultados falso-positivos na 68Ga-PSMA PET/CT no sistema musculoesquelético e ilustraremos os achados de imagem correspondentes.

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.

Response to Abemaciclib and Immunotherapy Rechallenge with Nivolumab and Ipilimumab in a Heavily Pretreated TMB-H Metastatic Squamous Cell Lung Cancer with CDKN2A Mutation, PIK3CA Amplification and TPS 80%: A Case Report.

Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.

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.

Musculoskeletal pitfalls in 68Ga-PSMA PET/CT / Pitfalls do sistema musculoesquelético na PET/CT com 68Ga-PSMA

Abstract Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in normal prostate cells and overexpressed in prostate cancer. Consequently, it is an important tool in the evaluation of prostate cancer, including the staging of high-risk patients and the assessment of biochemical recurrence. Despite the "specific" designation, benign musculoskeletal conditions, such as fractures, osteodegenerative changes, and fibrous dysplasia, can also show PSMA uptake, which can lead to misinterpretation of the imaging findings. Therefore, radiologists must be aware of these potential pitfalls, understand their causes, and fully analyze their morphologic features on unfused computed tomography (CT) and magnetic resonance imaging scans to correctly interpret the examination. In this pictorial essay, we review the basic characteristics of the 68Ga-PSMA positron-emission tomography/CT (PET/CT) radiotracer, discuss potential causes of false-positive findings on 68Ga-PSMA PET/CT in the musculoskeletal system, and illustrate the corresponding imaging findings.

Resumo O antígeno de membrana próstata específico (PSMA) é uma proteína transmembrana que apresenta expressão em células prostáticas normais e superexpressão em neoplasia da próstata. Dessa forma, é uma importante ferramenta na avaliação da neoplasia prostática, de utilidade no estadiamento de pacientes de alto risco e na análise de recorrência bioquímica. Apesar do termo "específico", condições musculoesqueléticas benignas podem demonstrar captação de PSMA, como fraturas, alterações osteodegenerativas e displasia fibrosa, podendo levar a uma avaliação equivocada dos achados de imagem. Assim, o radiologista deve conhecer esses potenciais pitfalls, compreender suas causas e analisar as características morfológicas nas imagens não fundidas de TC e RM para interpretar corretamente o exame. Neste ensaio iconográfico, revisaremos as características básicas do radiofármaco 68Ga-PSMA PET/CT, discutiremos possíveis causas de resultados falso-positivos na 68Ga-PSMA PET/CT no sistema musculoesquelético e ilustraremos os achados de imagem correspondentes.

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.

Prostate cancer recurrence in vas deferens - fusion image guide as an important tool in dignosis

ABSTRACT The biochemical recurrence after local treatment for prostate cancer is an often challenging condition of clinical management. The aim of this report is to demonstrate the importance of the association of various imaging methods in the identification and subsequent accurate percutaneous biopsy in patients with recurrence of prostate cancer, especially in unusual sites. An 86 years old male with biochemical recurrence, during radiological investigation a PET-MRI was noted the presence of an asymmetry of the vas deferens with PSMA-68Ga uptaken, suggesting the recurrence. A percutaneous fusion biopsy with PET-MRI and ultrasound was performed using transrectal access using ultrasound confirming infiltrating adenocarcinoma of the wall of the vas deferens, compatible with neoplastic prostate recurrence. The fusion image technique combines the real-time view of the US to the possibility of higher definition and higher specificity, methods more anatomical detail as tomography and magnetic resonance imaging, simultaneously. High resolution acquired in PET / MR associated with image fusion allows orientation procedures, even in areas of difficult access, with greater accuracy than conventional techniques.

Prostate cancer recurrence in vas deferens - fusion image guide as an important tool in dignosis.

The biochemical recurrence after local treatment for prostate cancer is an often challenging condition of clinical management. The aim of this report is to demonstrate the importance of the association of various imaging methods in the identification and subsequent accurate percutaneous biopsy in patients with recurrence of prostate cancer, especially in unusual sites. An 86 years old male with biochemical recurrence, during radiological investigation a PET-MRI was noted the presence of an asymmetry of the vas deferens with PSMA- 68Ga uptaken, suggesting the recurrence. A percutaneous fusion biopsy with PET-MRI and ultrasound was performed using transrectal access using ultrasound confirming infiltrating adenocarcinoma of the wall of the vas deferens, compatible with neoplastic prostate recurrence. The fusion image technique combines the real-time view of the US to the possibility of higher definition and higher specificity, methods more anatomical detail as tomography and magnetic resonance imaging, simultaneously. High resolution acquired in PET / MR associated with image fusion allows orientation procedures, even in areas of difficult access, with greater accuracy than conventional techniques.

Clinical utility of 18F-FDG PET/CT in the follow-up of a large cohort of patients with high-risk differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. SUBJECTS AND METHODS: Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). RESULTS: 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. CONCLUSION: 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.

Clinical utility of 18F-FDG PET/CT in the follow-up of a large cohort of patients with high-risk differentiated thyroid carcinoma

ABSTRACT Objective To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. Subjects and methods Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). Results 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. Conclusion 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.

Is PET-CT an accurate method for the differential diagnosis between chondroma and chondrosarcoma?

The differential diagnosis between chondroma and intraosseous chondrosarcoma is based on imaging and clinical exams, but only a biopsy can confirm diagnosis. The aim of this study was to evaluate the value of PET-CT in differentially diagnosing chondroma and chondrosarcoma. From October 2009 to May 2015, 36 patients with cartilaginous bone lesions in the extremities, 12 (33.3 %) men and 24 (66.6 %) women, were prospectively included in the study. Patients ranged in age from 21 to 68 years, with a mean age of 44 years. Lesions were located in the long bones: in the proximal humerus in 26 (72.2 %) patients, in the femoral shaft in 1 (2.7 %), in the distal femur in 7 (19.4 %), and in the proximal tibia in 2 (5.5 %). The SUVmax value of 2.0 was used to separate between patients submitted to surgery and patients submitted to observation. Among the 36 patients studied, 17 (47.2 %) had SUVmax ≤ 2.0, and they were diagnosed as chondroma and they were treated conservatively. Follow-up ranged from 14 to 76 months, averaging 38 months. Nineteen (52.7 %) patients with SUVmax >2.0 were diagnosed as chondrosarcoma and underwent surgery. The area of the curve, calculated considering the SUV variable as numeric, is estimated in 0.966, with a 95 % confidence interval from 0.906 to 1.000. To evaluate the sensitivity, specificity and positive/negative predictive values, it was built a 2 × 2 table. Significance was set at p < 0.05. According the criteria of maximum sensitivity and specificity, the cut point suggested to SUVmax was 2.2. If we consider this point, it is possible to identify 19 of 36 positive cases to chondroma (52.8 %), it means, all chondrosarcomas of the series. We concluded that PET-CT can be used as an objective and quantitative method of differentiating between chondromas and chondrosarcomas located within the long bones. It represents a complementary examination to standard imaging (X-ray, scintigraphy, CT and MRI) and pathological exams. The SUVmax between 2.0 and 2.2 would be a range area between chondroma and chondrosarcoma and this range can be of value, among others exams, in decide the best treatment for patients with cartilaginous lesions in long bones. Level of evidence Level I-diagnostic study-prospectively investigating a diagnostic test using a universally applied "gold" standard.

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.

Normalization of lymphocyte count after high ablative dose of I-131 in a patient with chronic lymphoid leukemia and secondary papillary carcinoma of the thyroid. Case report.

The authors report the case of a 70-year-old male patient with chronic lymphoid leukemia who presented subsequently a papillary carcinoma of the thyroid with metastases to regional lymph nodes. The patient was treated with surgical thyroidectomy with regional and cervical lymph node excision and radioiodine therapy (I-131). The protocolar control scintigraphy 4 days after the radioactive dose showed I-131 uptake in both axillae and even in the inguinal regions. PET/CT showed faint FDG-F-18 uptake in one lymph node of the left axilla. An ultrasound guided fine needle biopsy of this lymph node identified by I-131 SPECT/CT and FDG-F-18 PET/CT revealed lymphoma cells and was negative for thyroid tissue and thyroglobulin content. The sequential blood counts done routinely after radiation treatment showed a marked fall until return to normal values of leucocytes and lymphocytes (absolute and relative), which were still normal in the last control 19 months after the radioiodine administration. Chest computed tomography showed a decrease in size of axillary and para-aortic lymph nodes. By immunohistochemistry, cells of the lymphoid B lineage decreased from 52% before radioiodine therapy to 5% after the procedure. The authors speculate about a possible sodium iodide symporter expression by the cells of this lymphoma, similar to some other non-thyroid tumors, such as breast cancer cells.

Normalization of lymphocyte count after high ablative dose of I-131 in a patient with chronic lymphoid leukemia and secondary papillary carcinoma of the thyroid. Case report / Normalização da contagem de linfócitos após dose ablativa de I-131 em um paciente com leucemia linfóide crônica e carcinoma papilífero da tireóide. Relato de caso

The authors report the case of a 70-year-old male patient with chronic lymphoid leukemia who presented subsequently a papillary carcinoma of the thyroid with metastases to regional lymph nodes. The patient was treated with surgical thyroidectomy with regional and cervical lymph node excision and radioiodine therapy (I-131). The protocolar control scintigraphy 4 days after the radioactive dose showed I-131 uptake in both axillae and even in the inguinal regions. PET/CT showed faint FDG-F-18 uptake in one lymph node of the left axilla. An ultrasound guided fine needle biopsy of this lymph node identified by I-131 SPECT/CT and FDG-F-18 PET/CT revealed lymphoma cells and was negative for thyroid tissue and thyroglobulin content. The sequential blood counts done routinely after radiation treatment showed a marked fall until return to normal values of leucocytes and lymphocytes (absolute and relative), which were still normal in the last control 19 months after the radioiodine administration. Chest computed tomography showed a decrease in size of axillary and para-aortic lymph nodes. By immunohistochemistry, cells of the lymphoid B lineage decreased from 52% before radioiodine therapy to 5% after the procedure. The authors speculate about a possible sodium iodide symporter expression by the cells of this lymphoma, similar to some other non-thyroid tumors, such as breast cancer cells.

Os autores relatam o caso de um paciente de 70 anos com leucemia linfóide crônica que apresentou subsequentemente um carcinoma papilífero da tireóide com metástases para linfonodos regionais. O paciente foi tratado com tireoidectomia total cirúrgica com exérese de linfonodos regionais e cervicais e radioiodoterapia (I-131). A pesquisa de corpo inteiro protocolar de controle 4 dias após a dose radioativa mostrou captação de I-131 em ambas as axilas e mesmo nas regiões inguinais. PET/CT mostrou discreta captação de FDG-F-18 em um linfonodo da axila esquerda. A biópsia por agulha fina guiada por ultrassom deste linfonodo identificado por SPECT/CT com I-131 e PET/CT com FDG-F-18 revelou células linfomatosas e foi negativa para tecido tireoidiano e conteúdo de tireoglobulina. Os hemogramas sequenciais feitos rotineiramente após tratamento com radiações mostraram uma acentuada queda até retorno aos valores normais de leucócitos e de linfócitos (absolutos e relativos), que continuavam normais no último controle 19 meses após a administração do radioiodo. Tomografia computadorizada de tórax mostrou uma redução em tamanho de linfonodos axilares e para-aorticos. Por imunohistoquímica, as células da linhagem linfoide B decresceram de 52% antes da radioiodoterapia para 5% depois do procedimento. Os autores conjeturam sobre uma possível expressão de symporter de iodeto de sódio pelas células deste linfoma, à semelhança de outros tumores não tireoidianos, tais como células de câncer da mama.

Aspergillus fumigatus joint infection: a review.

OBJECTIVES: To describe a case of joint infection by Aspergillus fumigatus in a unusual site (sacroiliac) and perform a systematic review of such cases described in the literature. METHODS: We performed a Medline search of the cases of fungal joint of Aspergillus fumigatus in the period ranging from 1970 to 2009. RESULTS: Following PRISMA Guidelines, 15 cases including ours were reported during this period. Stem cell and solid organ transplantation, hematologic malignancy, and intra-articular steroids injection were the medical conditions found in such patients. The knee followed by the shoulder were the joints more affected. In the cases where synovial fluid analyses were reported, elevated cell count numbers could be found with a predominance of polymorphonuclear neutrophils. CONCLUSIONS: Fungal joint arthritis is a rare clinical disease most frequently present in immuno-incompetent patients. Rheumatologists should be aware of this condition, where early diagnosis can be associated with good prognosis.