Camparison of estimated glomerular filtration rate with serum creatinie and 51Cr-EDTA method in head and neck cancer patients treated with cisplatin

Orientador: Celso Dario RamosDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Objetivos: A avaliação da função renal, em particular da taxa de filtração glomerular (TFG), é extremamente importante em pacientes submetidos à quimioterapia com cisplatina, um fármaco nefrotóxico. Os objetivos deste trabalho foram comparar a estimativa da TFG pela fórmula Crockcroft-Gault (TFGe), que se baseia na creatinina sérica, com a TFG medida pelo método do EDTA-51Cr (TFG-EDTA), considerado "padrão-ouro", em pacientes com diagnóstico de carcinoma de cabeça e pescoço (CCP) antes e 30 dias após quimioterapia com cisplatina e acompanhar a evolução da função renal desses pacientes após 6 meses. Pacientes e Métodos: Foram avaliados 69 pacientes com diagnóstico de CCP submetidos à quimioterapia com cisplatina, sendo 6 mulheres e 63 homens. Esses pacientes foram submetidos ao exame com EDTA-51Cr e coleta de sangue para cálculo da TFGe antes e 30 dias após a quimioterapia. A função renal de 40 destes pacientes também foi analisada através da TFG-EDTA 6 meses após a quimioterapia. Resultados: A média da TFGe e TFG-EDTA pré-quimioterapia foi de 91,21 ml/min/1.73m2 e 84,33 ml/min/1.73m2, respectivamente. Trinta dias após a quimioterapia com cisplatina esta média foi de 78,79 ml/min/1.73m2 para a TFGe e 64,97 ml/min/1.73 m2 para a TFG-EDTA. A diferença entre os valores encontrados tanto pré-quimioterapia quanto pós-quimioterapia foi estatisticamente significante (p<0,0001). Nos 40 pacientes que tiveram a TFG acompanhada com EDTA-51Cr, foi encontrada média de 79,3, 60,9 e 64,9 ml/min/1.73m2, antes, 30 dias e 6 meses, respectivamente, após o tratamento com cisplatina. Conclusão: A medida da TFGe apresenta baixa acurácia para a avaliação da função renal em pacientes com CCP, tanto antes como imediatamente após o tratamento com cisplatina, e não pode ser recomendada como substituta do método com EDTA-51Cr. Há queda significativa da função renal após quimioterapia com cisplatina nestes pacientes e não ocorre recuperação completa da função renal 6 meses após o tratamento na maioria dos casosAbstract: Purpose: Renal function analysis, primarily glomerular filtration rate (GFR), is extremely important in patients undergoing chemotherapy with cisplatin, a nephrotoxic drug. The aim of this current study was to compare estimated TGF using the Crockcroft-Gault formula (eGFR) and the 51Cr-EDTA method EDTA-GFR), which is consider the "gold standard", in head and neck cancer (HNC) patients before and 30 days after chemotherapy with cisplatin. EDTA-GFR was also analysed 6 months after chemotheraphy. Materials and Methods: We evaluated 69 HNC patients who underwent chemotherapy with cisplatin (6 women and 63 men). These patients were submitted to 51Cr-EDTA plasma clearance and blood collection for eGFR calculation before and 30 days after chemotherapy. Forty of these patients had GFR examined by 51Cr-EDTA 6 months after chemotherapy. Results: The mean of eGFR and EDTA-GFR pre-chemotherapy was 91.21ml/min/1.73m2 and 84.33ml/min/1.73m2, respectively. Thirty days after chemotherapy with cisplatin the mean was 78.79ml/min/1.73 m2 for eGFR and 64.97ml/min/1.73m2 for EDTA-GFR. The difference between the values found pre and post-chemotherapy are statistically significant (p <0.0001). In the 40 patients who had GFR followed by 51Cr-EDTA, it was found a mean of 79.3, 60.9 and 64.9 mL/min/1.73m2, before, 30 days and 6 months after treatment with cisplatin, respectively. Conclusions: eGFR showed low accuracy in the assessment of renal function in patients with HNC, both before and immediately after cisplatin treatment, and cannot be recommended as a substitute to the method 51Cr-EDTA. There was a significant decrease in renal function after cisplatin chemotherapy in these patients and in the majority of the cases no recovery of renal function was observed 6 months after treatmentMestradoClinica MedicaMestra em Clínica Médic

99mtc sestamibi and 18f-fdg pet/ct for detection disease involvement in multiple myeloma

Orientador: Celso Dario RamosTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Objetivos: O PET/CT com FDG-18F tem sido amplamente utilizado no estadiamento e na avaliação prognóstica do mieloma múltiplo (MM). A cintilografia plana com Sestamibi-99mTc (MIBI-99mTc) também foi proposta como um potencial método para investigar o MM, entretanto, sua utilização com a tecnologia de última geração SPECT/CT não foi completamente avaliada. O objetivo deste estudo foi comparar essas duas modalidades de imagem no estadiamento do MM. Materiais e Métodos: Sessenta e dois pacientes com diagnóstico recente de MM [33 homens, idade média: 66 (39-87) anos] foram submetidos a PET/CT de corpo inteiro com FDG-18F e cintilografia de corpo inteiro com SPECT/CT do tórax e abdome com MIBI-99mTc. SPECT/CT da cabeça e pescoço foi realizado, quando necessário. Dados clínicos e laboratoriais habituais foram coletados e os pacientes foram acompanhados por uma média de 27,8 meses (± 23,4), mas dois deles perderam seguimento. Foram também avaliados o número de lesões focais (LF), o acometimento de partes moles por contiguidade (APMC), as lesões extramedulares (LEM) e o envolvimento difuso da medula óssea difusa (MO). Resultados: O PET/CT com FDG-18F foi positivo em 59 pacientes (95%) e o SPECT/CT com MIBI-99mTc em 58 (93%) (p=0,69). O MIBI-99mTc detectou mais envolvimento difuso da MO comparado ao PET/CT (78% vs. 58% dos pacientes, respectivamente), enquanto o PET/CT demonstrou mais LF que o MIBI-99mTc (81% vs. 54%) (p=0,002). O PET/CT detectou LEM em 4 pacientes e o MIBI-99mTc em 1. APMC foi observado em 28 (45%) e 23 (37%) dos pacientes no PET/CT e MIBI-99mTc, respectivamente (p=0,36). Três pacientes com lesões líticas sem hipercaptação de FDG-18F foram positivos no MIBI-99mTc, e 2 pacientes com lesões líticas sem aumento da captação no MIBI-99mTc eram FDG-18F positivos. A análise multivariada mostrou que no MIBI-99mTc, tanto a intensidade quanto a extensão da hipercaptação difusa na MO correlacionam-se com a sobrevida global e sobrevida livre de eventos. Conclusão: O SPECT/CT com MIBI-99mTc e o PET/CT com FDG-18F se assemelham na detecção de doença ativa no estadiamento do MM. O MIBI-99mTc é melhor que o FDG-18F na detecção de envolvimento difuso da MO. Os dois métodos parecem ser complementares em alguns pacientes, uma vez que um método pode detectar lesões não observadas pelo outro. O MIBI-99mTc pode ser útil na informação prognósticaAbstract: Purpose: 18F-FDG PET/CT has been widely used for staging and prognostic assessment of multiple myeloma (MM). 99mTc-Sestamibi (99mTc-MIBI) scintigraphy has also been proposed as a potential method for assessing MM, but its use with state-of-the-art SPECT/CT technology has not been fully evaluated. The aim of this study was to compare these two imaging modalities in MM staging. Materials and Methods: Sixty-two patients with recently diagnosed MM [male: 33 patients, median age: 66 (39-87) years] were submitted to whole body 18F-FDG PET/CT and whole body 99mTc-MIBI scan plus SPECT/CT of the chest and abdomen. Head and neck SPECT/CT was performed if necessary. Usual clinical and laboratory data were recorded, and patients were followed for 27,8 months (± 23,4), whereas 2 subjects were lost. Number of focal lesions (FL), contiguous soft tissue involvement (CSTI), extra medullary lesions (EML) and diffuse bone marrow (BM) involvement were recorded. Results: 18F-FDG PET/CT was positive in 59 patients (95%) and 99mTc-MIBI SPECT/CT in 58 (93%) (p=0.69). 99mTc-MIBI detected more diffuse BM involvement than PET/CT (78% vs. 58% of the patients, respectively), while PET/CT demonstrated more FL than 99mTc-MIBI SPECT/CT (81% vs. 54%) (p=0.002). PET/CT detected EML in 4 subjects and 99mTc-MIBI in 1. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and 99mTc-MIBI images, respectively (p=0.36). Three patients with lytic lesions and no 18F-FDG uptake were 99mTc-MIBI positive, and two subjects with lytic lesions without 99mTc-MIBI uptake were 18F-FDG positive. Multivariate analysis showed that both intensity and extension of diffuse BM uptake correlate with overall survival and event free survival. Conclusion: 99mTc-MIBI SPECT/CT performs similarly to 18F-FDG PET/CT in detecting sites of active disease in MM staging. 99mTc-MIBI is more successful than 18F-FDG in detecting diffuse BM involvement. Both methods seem to be complementary in some patients, since one method can detect lesions not observed by the other. 99mTc-MIBI may be useful in predicting prognosisDoutoradoClínica MédicaDoutora em Ciências001CAPE

Combined 18F-fluoride and 18F-FDG PET/CT scanning for evaluation of malignancy:results of an international multicenter trial

(18)F-FDG PET/CT is used in a variety of cancers, but because of variable rates of glucose metabolism, not all cancers are reliably identified. (18)F(-) PET/CT allows for the acquisition of highly sensitive and specific images of the skeleton. We prospectively evaluated combined (18)F(-)/(18)F-FDG as a single PET/CT examination for evaluation of cancer patients and compared it with separate (18)F(-) PET/CT and (18)F-FDG PET/CT scans. METHODS: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating (18)F(-) PET/CT, (18)F-FDG PET/CT, and combined (18)F(-)/(18)F-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. RESULTS: (18)F(-)/(18)F-FDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of (18)F-FDG PET/CT. In 19 participants, skeletal disease was more extensive on (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT than on (18)F-FDG PET/CT. In another 29 participants, (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT showed osseous metastases where (18)F-FDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans. CONCLUSION: This trial demonstrated that combined (18)F(-)/(18)F-FDG PET/CT shows promising results when compared with separate (18)F(-) PET/CT and (18)F-FDG PET/CT for evaluation of cancer patients. This result opens the possibility for improved patient care and reduction in health-care costs, as will be further evaluated in future trials

Predictive Factors of Failure in a Fixed 15 mCi I-131-Iodide Therapy for Graves' Disease

Purpose: To investigate the factors influencing the success rate in a fixed, 15 mCi approach for treatment of Graves' hyperthyroidism. Material and Methods: The thyroid function outcome ( hyperthyroidism or euthyroidism/hypothyroidism) was verified at least 1 year after radioiodine therapy (RIT) retrospectively and compared with presenting clinical characteristics and pre-RIT parameters in 87 patients treated with I-131-iodide for Graves' disease in a tertiary care center. Results: After RIT, 16 patients (18.4%) became euthyroid, 54 patients (62.1%) became hypothyroid, and 17 (19.5%) remained hyperthyroid. We found no statistically significant association between thyroid function outcome and gender (P = 0.50), ophthalmopathy (P = 0.69), drug used (methimazole or propylthiouracil; P = 1.00), maintenance or withdrawal of thionamides pre-RIT (P = 0.98), or Tc-99m sodium pertechnetate thyroid uptake prior to RIT (P = 0.75). The only variable associated with the success rate was thyroid mass 62 g.37655055

Proposal for a quantitative F-18-FDG PET/CT metabolic parameter to assess the intensity of bone involvement in multiple myeloma

Many efforts have been made to standardize the interpretation of F-18-FDG PET/CT in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of F-18-FDG PET/CT considering the extent and intensity of bone F-18-FDG uptake: Intensity of Bone Involvement (IBI). Whole body F-18-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with F-18-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement - PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = -0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação305110/2018-7; 311841/2018-02009/54065-0; 2018/00654-

Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies

<div><p>Purpose</p><p>(S)-4-(3-[¹⁸F]Fluoropropyl)-<i>L</i>-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure x_C^- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.</p><p>Experimental Design</p><p>For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.</p><p>Results</p><p>In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.</p><p>Conclusions</p><p>18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/results?term=NCT01186601" target="_blank">NCT01186601</a></p></div