(18)F-labelled metomidate analogues as adrenocortical imaging agents

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Organic Synthesis

Background:

• Development of novel fluorine-18 ((18)F)-labeled radiotracers is crucial for positron emission tomography (PET) imaging.
• Metomidate analogues are investigated for their potential in targeting the adrenal cortex.

Purpose of the Study:

• To synthesize and evaluate novel (18)F-labeled metomidate analogues for adrenocortical imaging.
• To compare the efficacy of two-step and one-step radiolabeling methods.

Main Methods:

• Synthesized five (18)F-labeled metomidate analogues using two-step and one-step radiolabeling strategies.
• Employed (18)F-fluoroethyl or (18)F-fluoropropyl tosylates as alkylating agents.
• Validated analogues 1-4 via frozen-section autoradiography and organ distribution studies; metabolite analysis for 2 and 3.

Main Results:

• Radiochemical yields for the two-step synthesis ranged from 10-29%, and for the one-step synthesis, 25-37%.
• Microwave irradiation significantly improved one-step yields for analogues 1 (46+/-3%) and 2 (79+/-30%).
• Analogue 2 exhibited the highest specific adrenal binding and the best adrenal-to-organ uptake ratio.

Conclusions:

• Analogue 2 shows significant potential as an adrenocortical imaging agent.
• The one-step synthesis, particularly with microwave assistance, offers improved radiochemical yields.
• Further investigation of analogue 2 is warranted for clinical application in adrenal imaging.