Patterns of recurrence following sentinel lymph node biopsy for cutaneous melanoma: outcome after 37 months of follow-up

BACKGROUND: Sentinel node biopsy (SNB) has been considered as an advance in surgical oncology for microstading melanoma. We report our experience with this procedure focusing on recurrence. METHODS: SNB was performed in 133 cutaneous melanoma patients submitted to preoperative lymphoscintigraphy, lymphatic mapping and gamma probe detection. Histologycal samples were analysed by HE and immunohistochemistry (IHC). RESULTS: The sentinel node was detected in 126 patients (96.2%). Micrometastasis were diagnosed in 20 patients (15.6%). There were nine recurrence, four in negative sentinel node group (108 patients). In this group, there was one systemic recurrence and three (2.8%) on lymphatic drainage region (false negative). In positive sentinel node group (20 patients) there were five recurrences. The recurrence was lower among negative sentinel node patients (p=0.0048). Ulceration (p=0.029) and positivity of the sentinel node (p=0.003) were considered significant risk factor by logistic analisys. Only sentinel node positivity maintained significance on multivariate analysis (p=0.024). The median follow up was 37 months. CONCLUSION: Patients with positive sentinel node presented more recurrence than negative sentinel node patients. The false negative rate was 2.8% and patients didn't have long-term sequelae ,allowing us to consider SNB as a secure and accurate procedure for melanoma staging.OBJETIVO: A biópsia de linfonodo sentinela (BLS) representa um avanço na cirurgia oncológica para o microestadiamento do melanoma. Apresentamos nossa experiência dando ênfase para a recorrência. MÉTODO: A BLS foi realizada em 133 pacientes portadores de melanoma cutâneo localizado envolvendo linfocintilografia, mapeamento linfático e detecção gama intra-operatórios em todos os pacientes. O exame histopatológico foi realizado por HE e imunohistoquímica (IHC). RESULTADOS: Encontrou-se LS em 128 pacientes (96,2%). Micrometástase foi diagnosticada em 20 pacientes (15,6%). Houve nove recorrências, sendo quatro no grupo com LS negativo (108 pacientes). Neste grupo, houve uma recorrência sistêmica e três (2,8%) na região linfática de drenagem (falso negativo). No grupo com LS positivo (20 pacientes) ocorreram cinco recorrências. Houve diferença significativa de recorrência entre os grupos, tendo sido menor no grupo LS negativo (p=0,0048). Através de análise de regressão logística univariada a ulceração (p=0,029) e a positividade do LS (p=0,003) apresentaram significância estatística como fatores de risco. Porém, apenas a positividade do LS manteve singificância na análise multivariada (p=0,024). O seguimento mediano foi de 37 meses. CONCLUSÕES: Pacientes com LS positivo apresentam recorrência significativamente maior que pacientes com LS negativo. O índice de falso negativo foi de 2,8% e os pacientes não apresentaram seqüelas o que permite considerar a BLS como procedimento seguro para o microestadiamento do melanoma cutâneo.UNIFESP-EPMCentro Avançado de Prevenção e Tratamento de CâncerHospital Israelita Albert EinsteinUniversidade de São PauloUNIFESP, EPMSciEL

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

The effect of catecholamines on the glucose uptake in brown adipose tissue demonstrated by F-18-FDG PET/CT in a patient with adrenal pheochromocytoma

Hosp Israelita Albert Einstein, Dept Imaging, Div Nucl Med, BR-05651901 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Endocrinol, São Paulo, BrazilWeb of Scienc

68GA-NOTA-UBI AND 68GA-DOTA-UBI AS RADIOPHARMACEUTICALS FOR THE DIAGNOSIS OF INFECTIOUS PROCESSES: PRECLINICAL STUDIES AND TRANSLATION TO CLINICAL APPLICATION

Introduction/Justification: Infectious diseases are the second leading cause of mortality worldwide. In this context, considerable efforts are being made to develop radiopharmaceuticals that enable the accurate diagnosis of bacterial infections. A new field of research is focusing on antimicrobial peptides, such as Ubiquicidin. The 29-41 fragment (Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg) UBI(29-41) labeled with radionuclides has proved to be an important tool for the specific diagnosis of infectious processes. Objectives: To present the radiochemical and ''in vitro'' studies of UBI(29-41) with the chelating agents 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for labeling with gallium-68 (68Ga) and to validate with a clinical application. Materials and Methods: After 68GaCl3 elution, the NOTA-UBI and DOTA-UBI reactions were performed at 85oC for 5 min and 95oC for 15 min, respectively. In both cases, the purification was carried out using a Sep-Pak C18 filter and radiochemical control by Thin-Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). The partition coefficient (Log P) and serum protein binding were determined, as well as the stability in saline and serum up to 90 min. After these studies, assays were carried out to determine the binding of the radiopharmaceuticals to ''Staphylococcus aureus'' bacteria. For the clinical study, the patient selected had a diagnosis of chronic osteomyelitis in the distal tibia, a positive blood culture for ''Staphylococcus aureus'' and a possible infectious/inflammatory process at the site identified by magnetic resonance imaging. The patient was injected intravenously with 281 MBq of 68Ga-DOTA-UBI to confirm the presence of an infectious process by PET-CT and the images were obtained 1 h post-administration. Resultados: The radiochemical purity (RP) of the radiopharmaceuticals after purification was 99.28±0.28% and 99.78±0.06% for 68Ga-NOTA-UBI and 68Ga-DOTA-UBI, respectively. Log P was -3.57±0.20 for 68Ga-NOTA-UBI and -3.63±0.17 for 68Ga-DOTA-UBI. Stability studies up to 90 min showed RP of 98.13±0.78% and 99.75±0.08% in saline; and 79.94±5.10% and 94.69±1.14% in serum, for 68Ga-NOTA-UBI and 68Ga-DOTA-UBI, respectively. The percentage of serum protein binding, evaluated at 30 and 60 min, was 59.90±1.21% and 53.45±2.16% for 68Ga-NOTA-UBI and 60.22±2.96% and 44.06±1.88% for 68Ga-DOTA-UBI, respectively. The binding of radiopharmaceuticals to ''Staphylococcus aureus'' revealed a direct relation to the amount of bacteria in the culture. Clinical images showed intense uptake of the radiopharmaceutical in the entire remnant of the talus and in the adjacent soft tissues of the left ankle. After scan, the secretion collected from the surgical site was cultured and the presence of ''Staphylococcus aureus'' was confirmed. Conclusion: The radiochemical and ''in vitro'' assays showed that the radiopharmaceuticals studied presented similar characteristics with the potential to be implemented in clinical practice. The clinical study showed that the UBI(29-41) fragment radiolabeled with 68Ga can be used as a potential biomarker for infectious processes, according to the availability of the chelating agent

AUTOMATED SYNTHESIS AND IN VITRO STUDIES OF [68GA]GA-FAPI-46 IN HOSPITAL RADIOPHARMACY

Introduction/Justification: Early evidence appointed fibroblast activation protein (FAP), a type II transmembrane serine protease, as highly expressed in the stroma of various tumor entities, designating FAP as the next target for cancer studies in nuclear medicine. Several radiolabeled fibroblast activation protein inhibitors (FAPI) are currently in development and investigation as potential PET imaging agents for different neoplasms, with the potential for future theranostic applications. Objectives: The aim of this study was to implement the efficient and convenient automated synthesis of [68Ga]Ga-FAPI-46 from ABX, using Modular Lab Pharm Tracer and the generator Gallia Pharm® from Eckert & Ziegler, for clinical applications in nuclear medicine services, as well as to evaluate routine quality control parameters such as radiochemical yield and purity, radiochemical stability, and sterility tests in accordance with the GMP rules. Materials and Methods: The synthesis was conducted in automated module, employing disposable cassettes in an adapted synthesis template with high purity raw materials and reagents. [68Ga]GaCl3 was percolated through resin and eluted with 0.5 mL of 5.5 M HCl in saline into a reaction vial containing 50 μg of FAPI-46 in 1.5 mL of 0.1 M acetate buffer (pH = 4.5) and 100 µL of ethanol. The solution was heated at 95°C for 10 min. The resulting product was purified through a Sep-Pak C18 cartridge, which was pre-conditioned with ethanol and 0.9% saline, and eluted with 0.4 mL of 70% ethanol. The final product was diluted with 0.9% saline and filtered through a Millipore 0.22 µm filter. Radiochemical yield (RCY) was assessed by determining the activity retained in the module in relation to the final product. Radiochemical purity (RCP) of [68Ga]Ga-FAPI-46 was analyzed by ascending chromatography using either ITLC-SG strip and 0.1 M ammonium acetate and methanol (1:1) solution or TLC and 1 M sodium citrate (pH = 5.5), and Sep-Pak C18 cartridge. Radiochemical stability was assessed through UHPLC analysis. Microbiological, pyrogenic, and filter tests were conducted on all batches. Additionally, in-vitro studies were carried out to assess Log P and serum protein binding for [68Ga]Ga-FAPI-46. Results: The automated synthesis produced [68Ga]Ga-FAPI-46 with an activity of 684 ± 67 MBq, a RCY of 88.4 ± 2.6%, and pH = 4.5 (n = 8). The RCP was determined as 97.32 ± 1.92% by ascending chromatography and 97.74 ± 2.12% by Sep-Pak C18 cartridge. The RCP remained above 97% for more than 120 min as analyzed by UHPLC, showing high radiochemical stability. Microbiological assays demonstrated that the final product was obtained as a sterile and pyrogen free solution. The filter test passed for all batches. The Log P was determined as -3.57 ± 0.15 (n = 10), showing the hydrophilic characteristics of [68Ga]Ga-FAPI-46 with a serum protein binding of 52.11 ± 1.49% (n = 6). Conclusion: The [68Ga]Ga-FAPI-46 was synthesized with consistently high RCY and RCP, exhibiting reproducibility, yielding a sterile and pyrogen free final solution, that means an efficient way for routine syntheses in nuclear medicine services confirmed by clinical application in six patients