Radionuclide therapy: current status and prospects for internal dosimetry in individualized therapeutic planning

The efficacy and toxicity of radionuclide therapy are believed to be directly related to the radiation doses received by target tissues; however, nuclear medicine therapy continues to be based primarily on the administration of empirical activities to patients and less frequently on the use of internal dosimetry for individual therapeutic planning. This review aimed to critically describe the techniques and clinical evidence of dosimetry as a tool for therapeutic planning and the main limitations to its implementation in clinical practice. The present article is a nonsystematic review of voxel-based dosimetry. Clinical evidence pointing to a correlation between the radiation dose and therapeutic response in various diseases, such as thyroid carcinoma, neuroendocrine tumors and prostate cancer, is reviewed. Its limitations include technical aspects related to image acquisition and processing and the lack of randomized clinical trials demonstrating the impact of dosimetry on patient therapy. A more widespread use of dosimetry in therapeutic planning involves the development of user-friendly dosimetric protocols and confirmation that dose estimation implies good efficacy and low treatment-related toxicity

Effect of salivary gland cooling in 68Ga-PSMA uptake

Introduction: Techniques using PSMA radioligands have emerged as diagnostic and therapeutic alternatives in prostate cancer. Significant adverse events resulting from using beta-emitters such as 177Lu-PSMA for castration-resistant prostate cancer therapy include sialotoxicity and xerostomia. Sialotoxicity ranges from 8% mild to moderate up to 10% interruption of treatment, depending on the compound used, due to the physiological expression of PSMA in the salivary glands and consequent radioligand uptake. Cooling with icepacks emerged as a possible intervention to prevent this event. The rationale is that cold- induced vasoconstriction would lead to a reduction of the perfusion of the gland, similarly to scalp cooling applied in some chemotherapies. Although empirically used in European protocols, the efficacy of this technique was assessed in only one study, with no evidence of success. The objective of this work was to analyze the efficacy of salivary gland cooling in the reduction of PSMA radioligand uptake.Methodology: Unilateral cooling of the salivary glands was performed for 10 prostate cancer patients submitted to PET-CT with Ga68PSMA, a compound used for diagnostic purposes and validated mainly in biochemical recurrence scenario. For cooling, icepacks were coupled to a device that attached them to one of the patient's parotid gland. Cooling started 30 minutes before the injection of the radiopharmaceutical. The test was started 1h after the injection (acquisition t1), with an approximate duration of 30 minutes. A delayed image was made 4h after the injection (acquisition t4). The cooling was suspended just after the t1 acquisition. The packs were replaced every 30 minutes, and their temperature measured and recorded using infrared thermometers, for temperature standardization. Using OsiriX Dicom Viewer software, each of the glands (cooled parotid and control, cooled submandibular and control) was quantitatively assessed by the standardized maximum, mean and peak uptake values (SUVmax, SUVmean, and SUVpeak). The gland was delimited through an isocontour generated from a threshold of 10% of the SUVmax within a defined volume of interest (VOI). These four parameters were compared through the paired Student's T-test using R Commander software.Results: There was no statistically significant reduction in any of the SUV parameters in the cooled glands compared to contralateral controls, both in t1 in t4. Regarding the submandibular glands, there were also found no alterations of statistical relevance, but the means of the three SUV parameters were higher in the cooled glands that in the controls.Discussion: Results indicated no significant reduction of the radiation absorbed dose by cooled salivary glands. Despite the small sample size, that could reduce the ability to detect significant variations, results allow inferring that biological effects, if present, are probably small and of little clinical significance. Therefore, it was considered that results did not justify performing further exams since this is a high cost and complexity technique. The present findings corroborate with the other mentioned study.Conclusion: The cooling of the salivary glands does not significantly reduce their uptake of radiopharmaceuticals, and no evidence supports this technique for sialotoxicity and xerostomia prevention in clinical practice

Câncer de próstata resistente à castração: estado atual do tratamento com Rádio-223 associado com anti-androgênios ( enzalutamida e abiraterona ) - uma revisão sistemática da literatura

INTRODUÇÃO. Recentemente, uma nova gama de opções terapêuticas tornou-se disponível para homens com câncer de próstata resistente à castração (CPRC), incluindo anti-androgênios (acetato de abiraterona, enzalutamida), taxanos (docetaxel, cabazitaxel) e um radionuclídeo (rádio-223). O desenvolvimento de abiraterona e enzalutamida, bem como o advento de Ra-223, levou a melhorias significativas nos resultados clínicos do CPRC. No entanto, existem atualmente poucos dados sobre a sequência ideal ou uso concomitante de Ra-223 com estes agentes endócrinos recentemente aprovados. OBJETIVO. Identificar e analisar sistematicamente os artigos que trazem informações sobre o uso concomitante ou sequencial de rádio-223 (Ra-223) associado com drogas antiandrogênicas (abiraterona ou enzalutamida) na terapia de CPRC. MÉTODOS. PubMed (mesh e termos livres), Scopus e ensaios clínicos foram utilizados para identificar artigos publicados sobre o uso sequencial ou associação de rádio-223 com anti-androgênios(enzalutamida e abiraterona). RESULTADOS. Um total de 484 referências foram identificadas pela pesquisa bibliográfica e, após aplicar critérios de exclusão e inclusão, 36 foram selecionadas. Quatro publicações que atenderam aos critérios de seleção foram incluídas nesta revisão; destas, 2 são estudos de custo-eficácia e 2 são séries de casos. No geral, os perfis de segurança em relação à terapia com Ra-223 foram semelhantes independentemente do uso ou não de enzalutamida ou de abiraterona. As taxas de resposta ao tratamento indicaram benefício na combinação de Ra-223 com abiraterona, mas a combinação com enzalutamida não indicou evidências positivas. As drogas não parecem ter grandes diferenças em relação à despesa total e ainda não há um consenso sobre o tratamento mais viável economicamente no curto e longo prazo. CONCLUSÃO. Mais estudos são necessários para avaliar a melhor eficácia do tratamento concomitante ou sequencial de Ra-223 com os novos anti-androgênios. Até agora, os dados mostram que a melhor associação pode ser com abiraterona. Há ensaios clínicos em curso que visam estudar precisamente o uso desses medicamentos em conjunto, portanto, nos próximos anos, essa situação tende a mudar.BACKGROUND. Recently, a new range of therapeutic options became available for men with advanced castration-resistant prostate cancer (CRPC), including antiandrogens (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and a radionuclide (radium-223). The development of abiraterone and enzalutamide, as well as the advent of Ra-223, led to significant improvements in CRPC clinical outcomes. However, there are currently few data regarding the optimal sequence or concomitant use of Ra-223 with these most recently approved endocrine agents. OBJECTIVE. To systematically identify and analyse articles that brings information about the concomitant or sequential use of radium-223 (Ra-223) associated with antiandrogenic drugs (abiraterone or enzalutamide) in the therapy of CRPC. METHODS. PubMed (mesh and free terms), Scopus and Clinical Trials were searched to identify published articles about the sequential or association use of radium-223. RESULTS. A total of 484 references were identified by the literature search and after exclusion and inclusion criteria 36 were screened. 4 publications that met the selection criteria were included in this review; of these 2 were cost-effectiveness studies and 2, case series. Overall, safety profiles in relation to therapy with Ra-223 were similar regardless of use or not of enzalutamide or abiraterone. Response were higher for the combinations of Ra-223 with abiraterone while with enzalutamide no improvements were found. The drugs do not seem to have great differences in costs and there is still no consensus on the most cost-effective treatment in the short and long term. CONCLUSION. Further studies are necessary to evaluate the best treatment regimen (concurrent or sequential) of Ra-223 and new antiandrogens. By now, data show that the best association of use may be with abiraterone. There are ongoing clinical trials that aim to precisely study the use of these drugs together, therefore in the next few years this situation tends to change

Glomerular Filtration Rate Measured by 51Cr-EDTA Clearance: Evaluation of Captopril-Induced Changes in Hypertensive Patients with and without Renal Artery Stenosis

INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis (51Cr-EDTA) and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m² in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m² in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m², p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m², p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show significant differences in differential renal function from baseline to post-captopril images in either group. CONCLUSIONS: Captopril induced a decrease in the GFR that could be quantitatively measured with 51Cr-EDTA. The reduction is more pronounced in hypertensive patients with RAS

Avaliação retrospectiva do tratamento da dor óssea metastática com Samário-153-EDTMP

PURPOSE: The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS: Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS: Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 ± 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). CONCLUSIONS: Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.OBJETIVO: O presente trabalho teve por objetivo avaliar o efeito paliativo da dor e a toxicidade medular associados ao tratamento com Samário-153-EDTMP em pacientes com metástases ósseas. MÉTODOS: O estudo foi realizado de forma retrospectiva, a partir do levantamento de prontuário de 178 pacientes submetidos a tratamento com 1mCi/kg de 153Sm-EDTMP devido à dor por metástases ósseas. Os prontuários de 73 pacientes foram considerados adequados para análise dos parâmetros clínicos (intensidade da dor) e laboratoriais (hemograma). A intensidade da dor foi avaliada em escala de 0 a 10 pelo próprio paciente, antes e durante 8 semanas após o tratamento. Hemograma completo foi realizado antes do tratamento e a cada semana nas 8 semanas seguintes. Estudos de dosimetria foram realizados em 41 dos 73 pacientes, baseados na excreção urinária e retenção do radioisótopo, sendo a dose de radiação absorvida correlacionada à toxicidade medular. RESULTADOS: Redução importante na intensidade da dor (diminuição de 75 a 100% do basal) foi constatada em 36 pacientes (49%), com redução de 50-75%, 25-50% e 0-25% em, respectivamente, 20 (27%), 10 (14%) e 7 (10%) casos. Não se observou variação significativa da resposta entre os pacientes com tumor primário de mama (n=29) ou de próstata (n=36). Toxicidade medular foi observada em 75,3% dos pacientes (71,2% com leucopenia e 53,4% com plaquetopenia), em geral de grau leve a moderado e com recuperação ao término da 8º semana. A dose média de medula foi de 347±65 cGy, havendo baixa correlação entre a dosimetria medular e a queda da contagem de leucócitos (coeficiente de correlação linear de 0,40) ou de plaquetas (coeficiente de correlação linear = 0,48). CONCLUSÕES: O tratamento com Samário-153-EDTMP permitiu um adequado controle da dor por metástases ósseas, com significativa redução na intensidade da dor. A toxicidade medular transitória foi a principal reação adversa observada, em geral de grau leve a moderado, apresentando baixa correlação com as medidas dosimétricas

Radioiodine therapy of differentiated thyroid cancer: radiologic impact of out-patient treatment with 100 to 150 mCi Iodine-131 activities

OBJETIVO: Determinar exposições decorrentes da radioiodoterapia ambulatorial do carcinoma diferenciado da tireoide (CDT) sobre os familiares dos pacientes e o meio ambiente. MÉTODOS: Administraram-se 100 a 150 mCi de (131I)NaI para tratamento ambulatorial de 20 pacientes com CDT. Monitorizaram-se com dosímetros termoluminescentes as doses de radiação recebidas por familiares (n = 27) e potenciais de dose nas residências. Também foram monitorizadas contaminação de superfície e rejeitos radioativos. RESULTADOS: Registraram-se doses < 1,0 mSv em 26 acompanhantes e 2,8 mSv em um caso, inferiores ao aceitável para exposições médicas (5,0 mSv/procedimento). Excetuando-se o quarto dos pacientes (média = 0,69 mSv), determinou-se potencial de dose nas residências < 0,25 mSv. A contaminação de superfícies (4,2 Bq.cm-2) não ultrapassou níveis de liberação, sem representar riscos mesmo em simulações do pior cenário. Os rejeitos radioativos tiveram volume de 2,5 litros e atividade estimada em 90 µCi (média = 4,5 µCi/paciente). CONCLUSÕES: Não foi constatado impacto radiológico ao meio ambiente ou aos familiares de pacientes tratados ambulatorialmente com 100 a 150 mCi de iodo-131 e acompanhados por profissionais qualificados.PURPOSE:To evaluate exposure and dosimetry to family members and environment due to outpatient radioiodine therapy of differentiated thyroid carcinoma. METHODS: Twenty patients were treated with 100-150mCi of iodine-131 on an out-patient basis. Family members dosimetry (n = 27) and potential doses inside the house were measured with thermoluminescent dosimeters. Surface contamination and radioactive wastes were also monitored. RESULTS: Less than 1.0 mSv doses were found in 26 co-habitants and 2.8 mSv in a single case (inferior to the acceptable value of 5.0 mSv/procedure). Potential doses in the houses were inferior to 0.25 mSv, excluding the patients bedroom (mean value = 0.69 mSv). Surface contamination (mean = 4.2 Bq.cm-2) were below clearance levels. Radioactive wastes generated had a volume of 2.5 liters and a total activity estimated in 90 µCi, with a calculated exposure close to the background radiation levels. CONCLUSIONS: No radiological impact was detected after iodine therapy with 100-150 mCi on an out-patient basis followed by experienced professionals.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Brown fat triglyceride content is associated with cardiovascular risk markers in adults from a tropical region

Brown adipose tissue (BAT) is regarded as an interesting potential target for the treatment of obesity, diabetes, and cardiovascular diseases, and the detailed characterization of its structural and functional phenotype could enable an advance in these fields. Most studies evaluating BAT structure and function were performed in temperate climate regions, and we are yet to know how these findings apply to the 40% of the world’s population living in tropical areas. Here, we used 18F-fluorodeoxyglucose positron emission tomography – magnetic resonance imaging to evaluate BAT in 45 lean, overweight, and obese volunteers living in a tropical area in Southeast Brazil. We aimed at investigating the associations between BAT activity, volume, metabolic activity, and BAT content of triglycerides with adiposity and cardiovascular risk markers in a sample of adults living in a tropical area and we showed that BAT glucose uptake is not correlated with leanness; instead, BAT triglyceride content is correlated with visceral adiposity and markers of cardiovascular risk. This study expands knowledge regarding the structure and function of BAT in people living in tropical areas. In addition, we provide evidence that BAT triglyceride content could be an interesting marker of cardiovascular risk

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.Univ Sao Paulo, Inst Canc Estado Sao Paulo, BR-01246000 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Radiol & Oncol, BR-01246903 Sao Paulo, BrazilHosp Sirio Libanes, BR-01308050 Sao Paulo, BrazilHosp Moinhos de Vento Porto Alegre, BR-90035000 Porto Alegre, RS, BrazilOncoctr, BR-30360680 Belo Horizonte, MG, BrazilUniv Fed Rio Grande do Sul, Dept Cirurgia, BR-90040060 Porto Alegre, RS, BrazilHosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Ceara, Fac Med, Dept Fisiol & Farmacol, BR-60020180 Fortaleza, Ceara, BrazilHosp Univ Walter Cantidio, BR-60430370 Fortaleza, Ceara, BrazilInst Nacl Canc, BR-20230240 Rio De Janeiro, BrazilUniv Sao Paulo, Fac Med, Disciplina Endocrinol & Metabol, BR-01246903 Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Surg, BR-01509010 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol, Sao Paulo, BrazilUniv Fed Ciencias Saude Porto Alegre, BR-90050170 Porto Alegre, RS, BrazilHosp Albert Einstein, BR-05652900 Sao Paulo, BrazilHosp Base, Fac Med Sao Jose do Rio Preto, BR-15090000 Sao Paulo, BrazilSanta Casa Sao Jose do Rio Preto, BR-15025500 Sao Jose Do Rio Preto, BrazilPontificia Univ Catolica Parana, Hosp Erasto Gaertner, BR-81520060 Curitiba, Parana, BrazilUniv Fed Rio Grande do Norte, BR-59300000 Natal, RN, BrazilUniv Sao Paulo, Inst Coracao, BR-05403900 Sao Paulo, BrazilAC Camargo Canc Ctr, Med Oncol, BR-01509010 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilHosp Sao Rafael, BR-41253190 Salvador, BA, BrazilHosp Canc Barretos, Dept Cirurgia Aparelho Digest Alto & Hepatobiliop, BR-14784400 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Patol, BR-01246903 Sao Paulo, BrazilClin AMO, BR-1950640 Salvador, BA, BrazilHosp Sao Jose, BR-01323001 Sao Paulo, BrazilUniv Nove de Julho, BR-02111030 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilWeb of Scienc