Follow-up of a case of subacute thyroiditis with uncommon thyroid (99m)Tc uptake.

Thyroidal 99mTc uptake in the acute thyrotoxic phase of subacute thyroiditis (SAT) is always inhibited. However, a patient with SAT had signs in the right-side thyroid gland with transient thyrotoxicosis and slightly high 99mTc uptake levels in the right lobe, low 99mTc uptake in the left lobe, and normal overall uptake. Histological examination showed cellular destruction and granulomatous inflammatory changes in the right lobe, with marked interstitial fibrosis in the left lobe. The patient was thyrotrophin-receptor antibody (TRAb) positive. After a short course of prednisolone, SAT-like symptoms and signs improved. TRAb-positivity resolved spontaneously after 22 months, and TSH levels were slightly low for 22 months. Levels then kept normal in the following four years. In conclusion, high 99mTc uptake by the right lobe was due to the combined effects of TRAb and left thyroid gland fibrosis.

Follow-up of a case of subacute thyroiditis with uncommon thyroid 99mTc uptake / Acompanhamento de caso de tiroidite subaguda com absorção incomum de 99mTc pela tiroide

Thyroidal 99mTc uptake in the acute thyrotoxic phase of subacute thyroiditis (SAT) is always inhibited. However, a patient with SAT had signs in the right-side thyroid gland with transient thyrotoxicosis and slightly high 99mTc uptake levels in the right lobe, low 99mTc uptake in the left lobe, and normal overall uptake. Histological examination showed cellular destruction and granulomatous inflammatory changes in the right lobe, with marked interstitial fibrosis in the left lobe. The patient was thyrotrophin-receptor antibody (TRAb) positive. After a short course of prednisolone, SAT-like symptoms and signs improved. TRAb-positivity resolved spontaneously after 22 months, and TSH levels were slightly low for 22 months. Levels then kept normal in the following four years. In conclusion, high 99mTc uptake by the right lobe was due to the combined effects of TRAb and left thyroid gland fibrosis.

A absorção tiroidiana de 99mTc no estado tirotóxico agudo da tireoidite subaguda (SAT) é sempre inibida. Entretanto, um paciente com SAT apresentou sinais na tiroide direita, com tirotoxicose transitória e níveis levemente elevados de 99mTc no lobo direito, baixa absorção de 99mTc no lobo esquerdo e absorção geral normal. O exame histológico mostrou destruição celular e alterações inflamatórias granulomatosas no lobo direito, com fibrose intersticial marcada no lobo esquerdo. O paciente foi positivo para anticorpos antirreceptores da tireotropina (TRAb). Após um curto tratamento com prednisolona, os sintomas e sinais da SAT melhoraram. A positividade para TRAb foi resolvida espontaneamente em 22 meses. Os níveis de TSH permaneceram levemente baixos por 22 meses e, depois, se mantiveram normais nos quatro anos seguintes. Concluiu-se que a alta absorção de 99mTc pelo lobo direito foi devida à combinação entre TRAb e fibrose da tiroide esquerda.

Radiotracers for different angiogenesis receptors in a melanoma model.

Early and reliable diagnosis of melanoma, a skin tumor with a poor prognosis, is extremely important. Phage display peptide libraries are a convenient screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was to evaluate two technetium-99m tracers for angiogenesis detection in a melanoma model, using cyclic pegylated pentapeptide with RGD and NGR motifs conjugated with the bifunctional chelator mercaptoacetyltriglycine (MAG(3)). The conjugated peptides (10 µl of a µg/µl solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was carried out by instant thin-layer chromatography and confirmed by high-performance liquid chromatography. The partition coefficient was determined and internalization assays were performed in two melanoma cell lines (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was carried out in healthy animals at different time points and also in tumor-bearing mice, 120 min post injection. Blocking studies were also conducted by coinjection of cold peptides. The conjugates displayed a rather similar pharmacokinetic profile. They were radiolabeled with high radiochemical purity (>97%) and both were hydrophilic with preferential renal excretion. Yet, tumor uptake was higher for human than for murine melanoma cells, especially for [(99m)Tc]-MAG(3)-PEG(8)-c(RGDyk) (7.85±2.34%injected dose/g 120 min post injection). The performance of [(99m)Tc]-MAG(3)-PEG(8)-c(RGDyk) was better than the NGR tracer with regard to human melanoma uptake. In this sense, it should be considered for future radiotracer studies of tumor diagnosis.

Modificación de la biodistribución de los glóbulos rojos marcados con 99mtc en la anemia ferropénica / Alteration in the biodistribution of 99mTc-RBC in an animal model of ferropenic anemia

Objetivo: Evaluar la biodistribución de 99mTc-GR en un modelo animal de anemia ferropénica. Materiales y métodos: Se utilizaron ratas alimentadas con dietas con diferente contenido de Fe: grupo A (anemia severa, 6.5 ppm), grupo B (anemia moderada, 18 ppm) y grupo C (control, 100 ppm). Se realizó la marcación in vivo de los 99mTc-GR y se evaluó la EBM y su biodistribución a los 30 minutos y a las 24 horas en sangre, hígado, bazo, tracto gastrointestinal, riñones, corazón y pulmones. Los resultados se expresaron como concentración de actividad porcentual (CA por ciento). Resultados: En todos los grupos la EBM fue superior al 98 por ciento. Se observó un aumento de CA por ciento en bazo a las 24 horas en el grupo A, acompañado de una disminución de la CA por ciento del pool sanguíneo posiblemente por aumento del secuestro esplénico de los GR. En los tres grupos hubo un aumento de la CA por ciento en riñón a las 24 horas. Conclusión: La biodistribución de 99mTc-GR se ve modificada en la anemia ferropénica.

Aim: To evaluate the biodistribution of 99mTc-RBC in an animal model of ferropenic anemia. Materials and methods: We used rats which were fed with different iron contents diets: group A (severeanemia, 6.5 ppm), group B (moderate anemia, 18 ppm) and group C (control, 100 ppm). We performed the in vivo labeling of RBC and evaluated the labeling efficiency and the biodistribution at 30 minutes and 24 hours in blood, liver, spleen, gastrointestinal tract, kidneys, heart and lungs. The results were expressed as activity concentration percentage (CA percent). Results: In all groups the labeling efficiency was higher than 98 percent. We observed an increase of CA percent in spleen at 24 hours in the group A, followed by a decrease of CA percent in blood. This could be a consequence of an increase of splenic uptake of RBC. An increase in CA percent in kidney was obtained at 24 hours for all the groups. Conclusion: An alteration in the RBC biodistribution is observed in an animal model of ferropenic anemia.

In vivo evaluation of three different 99mTc-labelled radiopharmaceuticals for sentinel lymph node identification.

This work was designed to compare sentinel lymph node (SLN) uptake of 99mTc-labelled human serum albumin colloid (99mTc-HSAC), 99mTc-labelled antimony sulphur colloid (99mTc-SC) and a 99mTc-labelled dextran 70 solution (99mTc-Dx) and their selectivity in the identification of this node in the right rear footpad (RRF) of normal mice and tumour bearing mice. Radiopharmaceutical uptake in the SLN (popliteal lymph node) and the lumbar lymph node (LLN), the second lymphatic node station from RRF, were measured at different time points post-intradermal or intratumoural injection into the RRF of NIH normal mice and of Balb/c mice harbouring the murine mammary tumour M2. 99mTc-HSAC uptake in the SLN was significantly higher than LLN uptake. The 99mTc-SC demonstrated high uptake in SLN, but accumulation in LLN was also high. 99mTc-Dx showed low uptakes in both SLN and LLN. The intradermal injection resulted in a more effective radiopharmaceutical accumulation in SLN than did the intratumoural inoculation. Data also show that increments in tumour volume reduced radiopharmaceutical uptake in the SLN. Our results show that 99mTc-HSAC exhibits the highest uptake in the SLN combined with the smallest amounts of radiopharmaceutical passing through to the LLN. Therefore, 99mTc-HSAC appears to be the best radiopharmaceutical for sentinel node detection.

Study of the toxicological effect of mitomycin C in mice: alteration on the biodistribution of radiopharmaceuticals used for renal evaluations.

Mitomycin C (MMC) has been used as a component of many chemotherapeutic regimens and some toxic effects of this substance have been reported. As it has been reported that the toxicological effect of a drug can alter the biodistribution of radiopharmaceuticals and because patients on chemotherapeutic treatment can be submitted to a nuclear medicine procedure, we investigated whether MMC could affect the uptake of various technetium-99m (99mTc) radiopharmaceuticals used for renal evaluations. The purpose of this study was to suggest a model to evaluate the toxic effect of substances in specific organs. Three doses of MMC (0.45 mg) were administered to mice (N=15). One hour after the last dose, 99mTc radiopharmaceuticals, 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA) or 99mTc-glucoheptonic acid (99mTc-GHA), with activity of 7.4 MBq, were also administered in the treated group and in the control group (N=15). After another 0.5 h, the animals were sacrificed. The organs were isolated, the 99mTc radiopharmaceutical uptake in the organs quantified in a well counter and the percentages of radioactivity (%ATI) calculated. The results have shown that: (i) with 99mTc-DTPA, the %ATI increased in the pancreas, ovary, uterus, stomach, kidney, spleen, thymus, heart, lung, liver, thyroid and bone; (ii) with 99mTc-DMSA, the %ATI decreased in all the organs except for the brain; and (iii) with 99mTc-GHA, the %ATI increased in the liver and decreased in the stomach, thymus, heart and thyroid. The effects of this chemotherapeutic drug on the biodistribution of these radiopharmaceuticals were statistically significant (Wilcoxon test, p<0.05) and could be explained by the metabolization and/or therapeutic action of MMC. Studies with other radiopharmaceuticals are in progress.

Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats.

The pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t 1/2alpha) of 0.250 h and a mean elimination (t 1/2beta) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99mTc-labeled humanized MAb R3 conjugate in patients should be supported.