RESUMO
We characterized T3 efflux in primary cultures of cells derived from human placenta, neonatal rat cardiac myocytes, and rat inner medullary collecting ducts (IMCD). The T3 efflux rate was highest in placenta cells, followed by ventriculocytes, atriocytes, and IMCD cells. Verapamil reversibly blocked [125I]T3 efflux in these cells in a manner that correlated with their T3 efflux rate. Thus, verapamil inhibition of [125I]T3 efflux in placenta cells led to a 432% increase in the [125I]T3 content compared with 33% increase in IMCD cells. Several unlabeled iodothyronines, but not TRIAC, differentially blocked [125I]T3 efflux such as (T4 > T3 > rT3 = D-T3 > D-T4) in placenta cells and (T4 > rT3 = D-T4 = T3 > D-T3) in ventriculocytes, suggesting tissue-specific differences in the carriers/transporters responsible for T3 efflux. This hypothesis draws further support from the fact that D-T3 inhibited [125I]T3 efflux in placenta cells, but not in ventriculocytes. TRIAC did not affect T3 efflux in ventriculocytes or placenta cells, but it greatly inhibited [125I]T3 uptake in these cells, suggesting that [125I]T3 uptake and efflux mechanisms are distinct and appear to be mediated by distinct carrier/transporter proteins. Collectively, these data suggest that differences in thyroid hormone transport in target cells may provide an important mechanism for regulating hormone action in a tissue-specific fashion.
Assuntos
Hormônios Tireóideos/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Córion/citologia , Córion/metabolismo , Decídua/citologia , Decídua/metabolismo , Feminino , Ventrículos do Coração/citologia , Ventrículos do Coração/metabolismo , Humanos , Indicadores e Reagentes , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Placenta/citologia , Placenta/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Tri-Iodotironina/metabolismo , Células Tumorais Cultivadas , Verapamil/farmacologiaRESUMO
PURPOSE: The use of I-123 in lieu of I-131 for diagnostic whole-body thyroid tumor scanning (DxRal) in patients with differentiated thyroid cancer obviates the risk for stunning and affords significantly improved image quality. Because of the shorter half-life (13 hours) of I-123, images have been acquired primarily 6 or 24 hours after injection, potentially decreasing the sensitivity for detecting weakly avid thyroid tumor or remnant. MATERIALS AND METHODS: The authors evaluated the use of 111 to 185 MBq (3 to 5 mCi) I-123 for DxRal under withdrawal conditions, imaging at 6, 24, and, in most cases, 48 hours. DxRal with I-123 was compared in 13 evaluations performed in 10 patients, with post-I-131 treatment scans acquired early (2 to 3 days) and late (7 to 10 days) in all cases but one. RESULTS: Of 37 sites of tumor or remnant identified in post-treatment scans, 26 were found in the DxRal I-123 scan (sensitivity, 70%). Of the 11 sites missed by I-123, 7 were seen only in the late post-treatment scans. Therefore, the sensitivity of I-123 imaging compared with the early post-I-131 treatment scans was 26 of 30, or 86.7%. In 10 cases, 48-hour I-123 imaging was attempted, yielding images of acceptable quality in eight of them. Lesion identification was improved on the 48-hour images; in one case, this allowed the identification of a site of tumor recurrence that was confirmed positive on the I-131 post-treatment scan. CONCLUSIONS: I-123 doses of 111 to 185 MBq for DxRal provide acceptable levels of sensitivity overall and may permit 48-hour imaging for improved detection of weakly avid tumor or remnant without any risk for "stunning."