LAT1 PET Tracer Composition for Tumor Retention and High-Yield Synthesis
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Solution Overview
Problem
Conventional tracer drugs for PET diagnosis targeting LAT1 have low selectivity and short retention at tumor sites, and their production methods using 18F—F2 gas result in low radioactivity and limited production amounts.
Innovation Solution
Introduce a methoxy group at the 4-position of the benzene ring of α-methyltyrosine to enhance selectivity and retention, and use 18F-hydrogen fluoride for efficient synthesis of the tracer compound via a novel intermediate with a boronic acid ester, allowing high-yield production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a conventional tracer drug targeting LAT1 is used, then the drug can be used for PET diagnosis, but the drug does not have high selectivity to LAT1 or has insufficient selectivity to tumor
Solution Approach 1:
The patent modifies the chemical structure of the tracer drug by introducing a methoxy group at the 4-position of the benzene ring of α-methyltyrosine. This local structural modification specifically enhances the interaction with LAT1 while maintaining tumor selectivity, thereby resolving the contradiction between measurement precision and reliability.
2Measurement precision
If 18F-FAMT is used as a tracer drug, then high selectivity to LAT1 is achieved, but the tracer drug disappears from tumor site at early stage
Solution Approach 1:
The patent changes the chemical parameter of the tracer drug by substituting the hydroxyl group at the 4-position of the benzene ring with a methoxy group. This parameter change reduces renal tubule incorporation while maintaining LAT1 selectivity, thereby improving retention at the tumor site without sacrificing selectivity.
3Ease of manufacture
If label synthesis using 18F—F2 gas is performed, then fluorine atom can be introduced into benzene ring, but the obtained radioactivity is small and production amount is limited
Solution Approach 1:
The patent changes the synthesis parameter by switching from 18F-F2 gas method to 18F-HF method. This parameter change enables efficient introduction of fluorine atom into the benzene ring while significantly increasing the obtained radioactivity and production amount, making the process suitable for widespread implementation in PET facilities.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The modified tracer compound exhibits improved accumulation and retention at tumor sites while maintaining high selectivity to LAT1, enabling accurate cancer diagnosis and efficient synthesis suitable for widespread implementation in PET facilities.
Implementation Method 1
a large neutral amino acid transporter called an L-type amino acid transporter 1 (LAT1) is known to act as an amino acid uptake port of cancer cells
Implementation Method 2
a hydroxyl group (OH group) at the 4-position of a benzene ring is easily incorporated into the renal tubules by interaction with an organic anion transporter (OAT1), and incorporation into the kidney is reduced by introducing an appropriate substituent for suppressing the interaction
Implementation Method 3
label synthesis (18F− method) using 18F-hydrogen fluoride (18F—HF)
Data Source
AI summary
Provided are a novel tracer drug for radioactive PET diagnosis having high accumulation properties and retention properties at a tumor site and an efficient production method of the tracer drug (label synthesis method).The present invention provides a novel tracer compound having improved accumulation and retention properties at a tumor site while maintaining high selectivity to an LAT1 by introducing a methoxy (OMe) group into the 4-position of a benzene ring of an α-methyltyrosine (AMT) skeleton. The present invention also provides a production method capable of efficiently synthesizing the novel tracer compound in high yield by a method of label synthesis using 18F-hydrogen fluoride (18F—HF) by using a novel labeled intermediate (precursor) obtained by introducing a boronic acid ester into the 3-position of the benzene ring of the AMT skeleton.