Abstract
Fusarinine C (FSC), a siderophore‐based chelator coupled with the model peptide c(RGDfK) (FSC(succ‐RGD)3), revealed excellent targeting properties in vivo using positron emission tomography (PET). Here, we report the details of radiolabeling conditions and specific activity as well as selectivity for 68Ga. 68Ga labeling of FSC(succ‐RGD)3 was optimized regarding peptide concentration, pH, temperature, reaction time, and buffer system. Specific activity (SA) of [68Ga]FSC(succ‐RGD)3 was compared with 68Ga‐1,4,7‐triazacyclononane, 1‐glutaric acid‐4,7 acetic acid RGD ([68Ga]NODAGA‐RGD). Stability was evaluated in 1000‐fold ethylenediaminetetraacetic acid (EDTA) solution (pH 7) and phosphate‐buffered saline (PBS). Metal competition tests (Fe, Cu, Zn, Al, and Ni) were carried out using [68Ga]‐triacetylfusarinine C.High radiochemical yield was achieved within 5 min at room temperature, in particular allowing labeling with 68Ga up to pH 8 with excellent stability in 1000‐fold EDTA solution and PBS. The 10‐fold to 20‐fold lower concentrations of FSC(succ‐RGD)3 led to the same radiochemical yield compared with [68Ga]NODAGA‐RGD with SA up to 1.8 TBq/µmol. Metal competition tests showed high selective binding of 68Ga to FSC.FSC is a multivalent siderophore‐based bifunctional chelator allowing fast and highly selective labeling with 68Ga in a wide pH range and results in stable complexes with high SA. Thus it is exceptionally well suited for the development of new 68Ga‐tracers for in vivo molecular imaging with PET.
Highlights
Positron emission tomography (PET) is one of the most prominent molecular imaging modalities, mainly based on the clinical utility of [18F]fluorodeoxyglucose
In contrast to 99mTc, which is widely used in clinical settings for single photon emission computed tomography and where a great number of structurally different chelating agents are available, less variety can be found for 68Ga, even though research in this field is very active increasing the number of chelating systems constantly.[2]
We focused on the optimization of radiolabeling conditions to reach the highest SA of [68Ga]fusarinine C (FSC)(succ-RGD)[3], to determine the stability of [68Ga]FSC(succ-RGD)[3] under different conditions, and to evaluate the influence of various metals on 68Ga labeling
Summary
Positron emission tomography (PET) is one of the most prominent molecular imaging modalities, mainly based on the clinical utility of [18F]fluorodeoxyglucose. DOTA is not ideally suited for Ga3+ having an effective ionic radius of 62 pm, comparable to Fe3+ (64.5 pm) and Zr4+ (72 pm) but considerably smaller than other radiometals used in the context of DOTA labeling such as In3+, Y3+, or lanthanides (La3+) with >80 pm.[3] An alternative chelating system for 68Ga is 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), which has a smaller cavity aDepartment of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria bDivision of Molecular Biology, Medical University Innsbruck, Innsbruck, Austria cDepartment of Nuclear Medicine, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
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