Tracer for derivative based on GnRH polypeptide as well as preparation method and application thereof

Abstract

The invention discloses a tracer for a derivative based on GnRH polypeptide as well as a preparation method and application thereof. A structural formula of the derivative based on the GnRH polypeptide is as follows: the formula is shown in the description, wherein R is a group containing a tracing atom. The derivative based on the GnRH polypeptide, disclosed by the invention, has good specificity; the intake amount of the derivative in visceral organs is relatively low and the background intake amount is relatively low; meanwhile, the derivative has a relatively high intake amount in tumor tissues in which GnRH receptors are highly expressed; especially, the derivative is suitable for being used as a tumor imaging agent. According to the tracer disclosed by the invention, PET (Polyethylene Terephthalate) imaging and in-vivo stability experiment results of bodies of nude mice bearing tumor show that the tracer has high tumor specificity and in-vivo stability.

Description

technical field [0001] The invention relates to an imaging tracer and a preparation method thereof, in particular to a tracer based on GnRH polypeptide derivatives, a preparation method and application thereof. Background technique [0002] Neuropeptide receptors are overexpressed on a variety of human tumors and have been used as molecular targets for tumor diagnosis and therapy. The specific accumulation of radiolabeled neuropeptide analogues in neuropeptide receptor-expressing tumors not only allows excellent tumor diagnosis, but also forms the basis of radiation therapy approaches. The somatostatin receptor is representative of successful peptide receptor targeting: the receptor in normal and tumor tissues, its function and its expression have been intensively studied, and an increasing number of optimized radionuclide-labeled receptors Ligands can be used in diagnostic and therapeutic applications 1 . [0003] The gonadotropin-releasing hormone receptor is a member o...

AI Technical Summary

Problems solved by technology

In 2010, Jalilian et al. prepared 111 In labeled GnRH derivatives [ 111 In]-DTPA-buserelin and biodistribution and SPECT imaging in normal rats (Formula 1), showed significant uptake in mammary gland and ovary, but this molecular probe was not further studied in tumor animals 5

In 2016, Zoghi et al. used positron nuclides 68 Ga-labeled GnRH derivative (DOTA-triptorelin) (IC 50 =0.22±0.05nM) as GnRH receptor PET imaging agent 7 , successfully prepared [ 68 Ga]-DOTA-triptorelin and biodistribution in normal rats and mice with 4T1, reported [ 68 Ga]-DOTA-triptorelin has a higher uptake in liver, kidney, spleen, lung, stomach, intestine, colon, muscle and testis tissue in rats (2h, uptake value ID / g%>2.9%), literature The uptake value of the tumor was not reported and no PET imaging experiment was carried out, and there were errors such as inconsistency between the graph and the text in the article, and the existing reported data showed [ 68 The background uptake value of Ga]-DOTA-triptorelin is too high and the specificity is poor, so it is not suitable as a PET imaging agent

[0009] Currently reported PET / CT molecular probes targeting GnRH receptors have defects such as high background uptake, poor selectivity, and low sensitivity.

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