Knee radiosynovectomy with 153Sm-hydroxyapatite compared to 90Y-hydroxyapatite: initial results of a prospective trial.

INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.

Radiosynoviorthesis in haemophilia: how safe?

One of the best procedures to prevent haemarthrosis in haemophilia has been radioactive synovectomy (radiosynoviorthesis). Since 1976 we have performed 119 radiosynoviortheses in 110 patients, aged from 3 to 40 years (mean 10), and of whom 71 were under 12 years of age. The knees were injected in 71, elbow in 29, ankles in 16, and shoulders in 3 cases. Clinical results of the procedure gave excellent results 80% of patients with no further bleeding. In the case of failure a reinjection can be given in the same joint at a 6 month interval. One of the criticisms against this method is possible chromosomal damage. In our centre, 4 studies have been made in order to see whether these changes are permanent, but all have demonstrated that chromosomal changes are reversible. Radioactive material used in 2 studies was Au-189. In 1978, 354 metaphases were studied with 61 ruptures, with 17.23% non-premalignant and 6 structural changes considered premalignant (1.69%). Further study was done in 1982, in the same group of patients with the result of 21 ruptures (3.34%) and no structural changes. The third study was performed in 13 patients that sustained radiosynoviorthesis with Re-186 in 1991. We compared the chromosomal study before and 6 months after the radioactive material injection and the results confirmed that changes appeared equally in non-irradiated and radiated patients and disappeared with time, never reaching the dangerous zone of 2%. In the group treated with Re-186 we studied an additional number of 130 metaphases with identical results and no structural changes. A study performed before and after radiosynoviorthesis with Y-90 revealed no premalignant changes. It seems than radiosynoviorthesis is safe and highly beneficial to haemophilic patients.

Optimal shielding design for bunkers of compact cyclotrons used in the production of medical radionuclides.

PURPOSE: There are several options to consider in the design of a vault that will house a cyclotron for radioisotopes production with regards to the door entrance. Alternatives are a direct-shielded door, a simple maze, or a double-legged maze. In this work, the impact of the neutron and photon doses at the vault entrance was evaluated for these options. METHODS: Monte Carlo simulations were carried out in order to assess photon and neutron ambient dose equivalents. Simulations results were compared to experimental measurements taken inside a vault with a direct-shielded door. RESULTS: The double-legged maze is the configuration that provides the higher degree of radiological protection at the vault entrance. In addition, the fact of the location of the cyclotron target plays an important role in the ambient dose equivalents. CONCLUSIONS: The comparison performed between measurements and results of MCNP simulations confirmed a favorable agreement; maze legs reduce the neutron energies at the entrances of the vault. However, a degree of dose reduction similar to the one obtained for a two-legged maze can be achieved with the addition of shielding against neutrons in the inner maze entrance to act as a second door. A choice of a vault design is more evident by comparing the results of this study.

Effectiveness of radiation synovectomy with samarium-153 particulate hydroxyapatite in rheumatoid arthritis patients with knee synovitis: a controlled randomized double-blind trial.

OBJECTIVES: The aim of the present study was to investigate the effectiveness of Samarium(153)-particulate hydroxyapatite radiation synovectomy in rheumatoid arthritis patients with chronic knee synovitis. METHODS: Fifty-eight rheumatoid arthritis patients (60 knees) with chronic knee synovitis participated in a controlled double-blinded trial. Patients were randomized to receive either an intra-articular injection with 40 mg triamcinolone hexacetonide alone (TH group) or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium(153)-particulate hydroxyapatite (Sm/TH group). Blinded examination at baseline (T0) and at 1 (T1), 4 (T4), 12 (T12), 32 (T32), and 48 (T48) weeks post-intervention were performed on all patients and included a visual analog scale for joint pain and swelling as well as data on morning stiffness, flexion, extension, knee circumference, Likert scale of improvement, percentage of improvement, SF-36 generic quality of life questionnaire, Stanford Health Assessment Questionnaire (HAQ), Lequesne index, use of non-steroidal anti-inflammatory drugs or oral corticosteroids, events and adverse effects, calls to the physician, and hospital visits. RESULTS: The sample was homogeneous at baseline, and there were no withdrawals. Improvement was observed in both groups in relation to T0, but no statistically significant differences between groups were observed regarding all variables at the time points studied. The Sm/TH group exhibited more adverse effects at T1 (p<0.05), but these were mild and transitory. No severe adverse effects were reported during follow-up. CONCLUSION: Intra-articular injection of Samarium(153)-particulate hydroxyapatite (15 mCi) with 40 mg of triamcinolone hexacetonide is not superior to triamcinolone hexacetonide alone for the treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of follow-up.

Whole-body measurements at Ipen, Brazil.

The intake of radioactive material by workers can occur in the radiopharmaceuticals production or during the handling of these in the medical fields (nuclear medicine). The workers who work in areas where exposures are significant are routinely monitored to demonstrate that the workers are receiving adequate protection from internal contamination. Direct measurements of whole-body and thyroid contents provide an estimate of the activity value of these radionuclides in the potentially exposed workers. The whole-body measurements of the workers, trainees and visitors are routinely performed by the In Vivo Monitoring Laboratory (LMIV) of the Energy and Nuclear Research Institute (IPEN/CNEN-SP). The frequency of measurements is defined by the Radioprotection Service (SRP) and the Dose Calculation Group of IPEN. During the period 2006-2007, 2500 measurements had been carried in workers who develop tasks related to the production of radiopharmaceuticals. The activity value of the radionuclides and the workers' tasks relationship had been evaluated.

Effectiveness of radiation synovectomy with samarium-153 particulate hydroxyapatite in rheumatoid arthritis patients with knee synovitis: a controlled randomized double-blind trial

OBJECTIVES: The aim of the present study was to investigate the effectiveness of Samarium153-particulate hydroxyapatite radiation synovectomy in rheumatoid arthritis patients with chronic knee synovitis. METHODS: Fifty-eight rheumatoid arthritis patients (60 knees) with chronic knee synovitis participated in a controlled double-blinded trial. Patients were randomized to receive either an intra-articular injection with 40 mg triamcinolone hexacetonide alone (TH group) or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium153-particulate hydroxyapatite (Sm/TH group). Blinded examination at baseline (T0) and at 1 (T1), 4 (T4), 12 (T12), 32 (T32), and 48 (T48) weeks post-intervention were performed on all patients and included a visual analog scale for joint pain and swelling as well as data on morning stiffness, flexion, extension, knee circumference, Likert scale of improvement, percentage of improvement, SF-36 generic quality of life questionnaire, Stanford Health Assessment Questionnaire (HAQ), Lequesne index, use of non-steroidal anti-inflammatory drugs or oral corticosteroids, events and adverse effects, calls to the physician, and hospital visits. RESULTS: The sample was homogeneous at baseline, and there were no withdrawals. Improvement was observed in both groups in relation to T0, but no statistically significant differences between groups were observed regarding all variables at the time points studied. The Sm/TH group exhibited more adverse effects at T1 (p<0.05), but these were mild and transitory. No severe adverse effects were reported during follow-up. CONCLUSION: Intra-articular injection of Samarium153-particulate hydroxyapatite (15 mCi) with 40 mg of triamcinolone hexacetonide is not superior to triamcinolone hexacetonide alone for the treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of follow-up.

Investigation of the radiation risk due to environmental contamination by 241Am from lightning rods disposed at uncontrolled garbage dumps.

Radioactive lightning rods were manufactured in Brazil until 1989, when the licenses for using radioactive sources in these products were lifted by the national nuclear authority. Since then, these rods have been replaced by the Franklin type and collected as radioactive waste. However, only 20% of the estimated total number of installed rods has been delivered to the Brazilian Nuclear Commission. This situation causes concern, since there is the possibility of the rods to be disposed as domestic waste. In Brazil, 64% of the municipal solid waste is disposed at garbage dumps without sufficient control. In addition, (241)Am, the radionuclide most commonly employed, is classified as a high-toxicity element, when incorporated. In the present study, (241)Am migration experiments were performed by means of a lysimeter system, in order to evaluate the risk of contamination caused by radioactive lightning rods disposed as common solid waste. (241)Am sources removed from lightning rods were placed inside lysimeters filled with organic waste that was collected at the restaurant of the Instituto de Pesquisas Energéticas e Nucleares. The generated leachate was periodically analyzed, and characteristics such as pH, redox potential, solid content and the concentration of the radioactive material were determined. The equivalent dose for members of the public was calculated considering ingestion of contaminated drinking water as the major path of exposure. Estimated doses were about 20-times below the effective dose limit of 1 mSv year(-1) for members of the public as recommended by the International Commission on Radiological Protection. This suggests the radiation risk caused by lightning rods disposed at uncontrolled garbage dumps to be low. It should be noted, however, that the number of investigated lightning rods was quite small. The results of this study might therefore not be entirely representative and should be interpreted with care. They provide, however, a very first basis for characterizing the transfer of (241)Am from lightning rods to the human food chain.

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188 Re in adult recurrent high-grade glioma.

Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase I clinical trial was performed to evaluate, for the first time, the toxicity and clinical effect of an intracavitary administration of a single dose of Nimotuzumab (h-R3) labeled wit (188)Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Three patients with anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of (188)Re. In patients treated with 10 mCi (n=6) transitory worsening of pre-existing neurological symptoms were observed. Two patients treated with 15 mCi (n=4) developed early severe neurological symptoms and one also developed late severe toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed stable disease during 3 months. One GBM patient had partial response for more than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete response after 3 years of treatment. Maximal tolerated dose of the radioimmunoconjugate (188)Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10 mCi of (188)Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5 % of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas.

Intra-arterial rhenium-188 lipiodol in the treatment of inoperable hepatocellular carcinoma: results of an IAEA-sponsored multination study.

PURPOSE: Intra-arterial injections (IAI) of 131I-lipiodol is effective in treating hepatocellular carcinoma patients, but is expensive and requires a 7-day hospitalization in a radioprotection room. 188Re is inexpensive, requires no patient isolation, and can be used with lipiodol. METHODS AND MATERIALS: This International Atomic Energy Agency-sponsored phase II trial aimed to assess the safety and the efficacy of a radioconjugate 188Re + lipiodol (188Re-Lip) in a large cohort of hepatocellular carcinoma patients from developing countries. A scout dose is used to determine the maximal tolerated dose (lungs <12 Gy, normal liver <30 Gy, bone marrow <1.5 Gy) and then the delivery of the calculated activity. Efficacy was assessed using response evaluation criteria in solid tumor (RECIST) and alpha-feto-protein (alpha FP) levels and severe adverse events were graded using the Common Toxicity Criteria of the National Cancer Institute scale v2.0. RESULTS: The trial included 185 patients from eight countries. The procedure was feasible in all participating centers. One treatment was given to 134 patients; 42, 8, and 1 received two, three, and four injections, respectively. The injected activity during the first treatment was 100 mCi. Tolerance was excellent. We observed three complete responses and 19 partial responses (22% of evaluable patients, 95% confidence interval 16-35%); 1- and 2-year survivals were 46% and 23%. Some factors affected survival: country of origin, existence of a cirrhosis, Cancer of the Liver Italian Program score, tumor dose, absence of progression, and posttreatment decrease in alpha FP level. CONCLUSIONS: IAI of 188Re-Lip in developing countries is feasible, safe, cost-effective, and deserves a phase III trial.

Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with samarium-153 in hypercholesterolemic rabbits.

OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11% and 15-Gy IG: 14.29%, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33% and 15-Gy IG:0%, p=0.0001) and vascular proliferation (60-Gy IG:30.56% and 15-Gy IG:0%, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.

Radiolesão vascular como efeito deletério da braquiterapia intra-arterial com dose elevada de Samário-153 em coelhos hipercolesterolêmicos / Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with Samarium-153 in hypercholesterolemic rabbits / Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with Samarium-153 in hypercholesterolemic rabbits

OBJETIVO: Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com Samário-153 (153 Sm) em coelhos hipercolesterolêmicos, com doses elevadas. MÉTODOS: Foram analisados 43 coelhos hipercolesterolêmicos, brancos, da raça New Zealand, e o total de 86 artérias ilíacas submetidas a lesão por balão de angioplastia. Divididos em três grupos: dois (GI) irradiados com as doses de 15Gy (n=14) e 60Gy (n=36) e um grupo controle (n=36). Foram realizadas avaliação histológica morfométrica e análise histológica qualitativa para análise tecidual. RESULTADOS: Foram observadas uma redução significativa da neoproliferação intimal (NPI) no GI 15 Gy (p<0,0001), uma redução da área de camada média (ACM) (p<0,0001) e por cento estenose (p<0,0001) comparada com os demais grupos. O GI 60 Gy teve o maior índice de PNI, aumento da ACM, AV e porcentagem de estenose. No GI 60 Gy, observou-se maior número de células xantomatosas (GI 60Gy:86,11 por cento e GI 15Gy:14,29 por cento, p<0,0001), tecido amorfo hialino (GI 60Gy:58,33 por cento e GI 15 Gy:0 por cento, p=0,0001) e proliferação vascular (GI60 Gy:30,56 por cento e GI15 Gy:0 por cento, p=0,0221). Outras análises teciduais não apresentaram diferença estatística entre os grupos. CONCLUSÃO: A dose elevada de 60Gy ocasionou intensa proliferação celular considerada radiolesão vascular, ao contrário da dose de 15Gy que apresentou excelente inibição da neo-proliferação intimal.

OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11 percent and 15-Gy IG: 14.29 percent, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33 percent and 15-Gy IG:0 percent, p=0.0001) and vascular proliferation (60-Gy IG:30.56 percent and 15-Gy IG:0 percent, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.

Cytogenetic research after accidental radiation exposure.

Currently, chromosome aberration analysis in peripheral lymphocytes is the most sensitive method to estimate individual doses in accidental radiation exposures. The assessment of dose is particularly reliable in cases with acute, uniform, whole-body exposure or after irradiation of large parts of the body. However, the scenarios of most radiation accidents largely result in partial-body exposures or a non-uniform dose distribution. This complicates dose estimation especially in cases with protracted or fractionated exposures. Problems exist also for the dose reconstruction of radiation exposures occurring a long time before sampling. To overcome these problems, the Qdr method or the "contaminated Poisson" method can be used to determine meaningful dose estimates from data based on conventional scoring of dicentrics. Scoring of so-called stable translocations by the newly developed technique of chromosome painting should be particularly useful for estimating doses of past exposures or of dose accumulation. After incorporation of radionuclides with largely localized depositions in certain organs or tissues, realistic individual dose estimates cannot be achieved. Exemplified by incidents involving larger groups of the population such as in Chernobyl and Goiania and by single cases with serious overexposures, chromosome dosimetry is evaluated in the present article.