Technetium-99m-sestamibi uptake by human benign and malignant breast tumor cells: correlation with mdr gene expression.
J Nucl Med
; 37(2): 286-9, 1996 Feb.
Article
em En
| MEDLINE
| ID: mdl-8667063
ABSTRACT
UNLABELLED Early diagnosis of multidrug-resistance (MDR) development is extremely important for the judicious choice of treatment protocols in breast cancer chemotherapy. In this study, the mechanism of 99mTc-sestamibi uptake by nine human breast tumor cell lines was analyzed as a function of P-glycoprotein (PgP) expression. METHODS:
Technetium-99m-sestamibi radioactivity incorporation into the cells was determined after different times of incubation at 37 degrees C. We analyzed the mechanism of 99mTc-sestamibi uptake as follows (a) effect of temperature (4 degrees C); (b) influence of extracellular 99mTc-sestamibi concentration; and (c) competitive inhibition of cell uptake with cold 99mTc-sestamibi. Technetium-99m-sestamibi uptake was compared to the level of PgP determined by Western blotting. The PgP reversing effect of verapamil was evaluated at different drug concentrations (50, 200, 500 microM).RESULTS:
Technetium-99m-sestamibi uptake plateaued at 60 min, which was 14 times lower at 4 degrees C than at 37 degrees C and was directly proportional to the extracellular concentration between 0.3 and 10 nM. Technetium-99m-sestamibi percentage uptake by cells expressing nonimmunodetectable levels of PgP was significantly higher (7.3% +/- 0.6% (s.d.) to 14.9% +/- 1.9%) than that by cells expressing high PgP levels (0.7% +/- 0.4%, p < 0.001). In the presence of verapamil, a known reverser of PgP functions, 99mTc-sestamibi uptake was increased by a factor of 2 in cells expressing no detectable levels of PgP and by a factor of 12 in cells with high PgP levels.CONCLUSION:
Technetium-99m-sestamibi uptake by these breast tumor cells is energy-dependent but not specific. These data suggest that 99mTc-sestamibi imaging may be used as a noninvasive technique to diagnose the presence of MDR in breast tumors in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
Tecnécio Tc 99m Sestamibi
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistência a Múltiplos Medicamentos
Tipo de estudo:
Guideline
/
Screening_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article