On the shoulder of ADC: The development of 124I-IMMU-132, an iodine-124-labelled Trop-2-targeting molecular probe for micro-PET imaging.
Biomed Pharmacother
; 178: 117151, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39029403
ABSTRACT
BACKGROUND:
Trop-2 is closely related to the development and progression of a variety of tumours and poor prognosis. This study aimed to construct an iodine-124 (124I)-labelled antibody-drug conjugate (ADC) positron emission tomography (PET) probe which could noninvasively image Trop-2 in vivo, providing an important method for the diagnosis of tumours with high Trop-2 expression in clinical practice and monitoring their treatment.METHODS:
In this study, a novel Trop-2-targeting molecular probe, 124I-IMMU-132, was constructed to better reveal the expression of Trop-2. The targeting and binding abilities of the probe to Trop-2-positive tumours were investigated in Capan-1/MDA-MB-468/Mcf-7 cells and their animal models.RESULTS:
The constructed 124I-IMMU-132 probe maintained both reliable radiochemical characteristics and binding affinity (Kd = 2.200 nmol/L). The uptake of the probe by Trop-2-positive Capan-1/MDA-MB-468 cells increased in a time-dependent manner. The probe bound specifically to Capan-1/MDA-MB-468 tumours in vivo. The SUVmax Tumour/muscle ratio gradually increased with time, from 4.30 ± 0.55-10.78 ± 1.80 (p < 0.01) in the Capan-1 model and from 8.84 ± 0.95-32.20 ± 2.9 (p < 0.001) in the MDA-MB-468 model. The biodistribution and pharmacokinetics of 124I-IMMU-132 in a mouse model were consistent with the imaging results, and the dosimetry estimation in humans was acceptable.CONCLUSIONS:
124I-IMMU-132 PET is a promising imaging technique for delineating Trop-2-positive tumours. It has great potential in early diagnosis and targeted selection of patients that could benefit from its application.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sondas Moleculares
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Moléculas de Adhesión Celular
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Inmunoconjugados
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Tomografía de Emisión de Positrones
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Radioisótopos de Yodo
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Antígenos de Neoplasias
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2024
Tipo del documento:
Article