Evaluation of radioiodinated quinazoline derivative as a new ligand for EGF receptor tyrosine kinase activity using SPECT.
Ann Nucl Med
; 25(2): 117-24, 2011 Feb.
Article
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| MEDLINE
| ID: mdl-21058048
ABSTRACT
OBJECTIVE:
A radioiodinated analog of PD153035 (m-IPQ) was evaluated as a potential epidermal growth factor receptor tyrosine kinase (EGFR-TK) activity imaging ligand for SPECT.METHODS:
The 50% inhibition concentration (IC50) value of m-IPQ for EGFR-TK phosphorylation inhibition was evaluated and compared to various EGFR-TK inhibitors. [(125)I]m-IPQ was synthesized by iododestannylation reaction. Biodistribution study of [(125)I]m-IPQ was conducted in normal mice and tumor-bearing mice. The selectivity and binding characteristics (B(max) and K(d)) were analyzed.RESULTS:
The quinazoline derivative m-IPQ was found to have high inhibitory potency (IC50 50.5 ± 3.5 nM) and selectivity toward EGFR-TK. In vivo biodistribution studies of [(125)I]m-IPQ demonstrated its rapid clearance and low retention in normal tissue. On the other hand, high tumor uptake was observed. However, the increase in [(125)I]m-IPQ uptake in the stomach as a deiodination parameter was found. Thus, [(125)I]m-IPQ showed low in vivo stability. The selectivity toward EGFR-TK of m-IPQ was confirmed by the pretreatment experiment with EGFR-TK specific inhibitors, PD153035, Genistein. [(125)I]m-IPQ bound to single population of binding sites with high affinity and kinetic parameter. In addition, [(125)I]m-IPQ was bound to EGFR-TK according to the amount of EGFR-TK expression in the tumor.CONCLUSIONS:
[(125)I]m-IPQ showed a relatively high tumor accumulation with selective EGFR-TK binding. Moreover, the tumor uptake of [(125)I]m-IPQ might be reflected in the amount of EGFR-TK expression in the tumor. These good characteristics of [(125)I]m-IPQ suggested that a ¹²³I-labeled counterpart, [¹²³I]m-IPQ, would have great potential for EGFR-TK imaging with SPECT. However, the in vivo stability of this compound needs to improve.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
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Tomografía Computarizada de Emisión de Fotón Único
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Inhibidores de Proteínas Quinasas
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Receptores ErbB
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Ann Nucl Med
Asunto de la revista:
MEDICINA NUCLEAR
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón