Background Accurate assessment of liver function and biliary excretion is a key aspect in the medical and surgical management of various liver conditions. Dynamic nuclear imaging techniques such as PET (positron emission tomography) offer the potential to directly quantify hepatic clearance and hepatobiliary function. Indocyanine green (ICG) is a fluorescent dye that is used to indirectly evaluate liver function via its plasma clearance, but its optical properties preclude deep tissue imaging. Here, we report the synthesis and preclinical evaluation of a novel fluorine-18 labeled ICG derivative ([18F]SFB-ICG; SFB = N-succinimidyl-4-[18F]fluorobenzoate) as a potential PET radiotracer for noninvasive assessment of hepatobiliary function. Results ICG was successfully labeled with 18F: The product was obtained in high chemical and radionuclidic purity, albeit in relatively low yield (0.25–1.0%, non-decay-corrected). PET imaging demonstrated rapid hepatic uptake with a peak standardized uptake value (SUV) of 8.6 ± 0.8 at 20 min post-injection. The tracer exhibited prompt biliary excretion as demonstrated by a gallbladder SUV of 22.3 ± 1.4 at 45 min post-injection. Time–activity curves confirmed hepatic clearance similar to unlabeled ICG. At 4 h PI, the SUVs of selected organs were: liver 4.7 ± 0.5; lungs 0.15 ± 0.02; small intestine 3.68 ± 0.76; spleen 2.25 ± 0.88; large intestine 4.9 ± 1.7. Renal uptake and clearance was minimal. The whole blood SUV at 1 and 4 h post-injection was 0.47 ± 0.04 and 0.20 ± 0.02, respectively. No overt adverse effects were observed during the 4-h study period. Conclusions This study presents [18F]SFB-ICG as a novel PET tracer for real-time, quantitative assessment of liver function and biliary clearance in vivo. The tracer exhibits favorable pharmacokinetics, high liver specificity, and excellent correlation with established hepatobiliary physiology. Thus, 18F-SFB-ICG represents a lead compound that warrants further development—including yield optimization, stability and toxicity characterization, and evaluation in animal models of liver disease—for potential applications in hepatic functional imaging, surgical planning, characterization of liver masses, and assessment of biliary pathology.

Preclinical evaluation of a fluorine-18-labeled indocyanine green analog for PET imaging of hepatic function

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2026年6月16日

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Khashayar Vakili,
Alan Packard

摘要

Background

Accurate assessment of liver function and biliary excretion is a key aspect in the medical and surgical management of various liver conditions. Dynamic nuclear imaging techniques such as PET (positron emission tomography) offer the potential to directly quantify hepatic clearance and hepatobiliary function. Indocyanine green (ICG) is a fluorescent dye that is used to indirectly evaluate liver function via its plasma clearance, but its optical properties preclude deep tissue imaging. Here, we report the synthesis and preclinical evaluation of a novel fluorine-18 labeled ICG derivative ([¹⁸F]SFB-ICG; SFB = N-succinimidyl-4-[¹⁸F]fluorobenzoate) as a potential PET radiotracer for noninvasive assessment of hepatobiliary function.

Results

ICG was successfully labeled with ¹⁸F: The product was obtained in high chemical and radionuclidic purity, albeit in relatively low yield (0.25–1.0%, non-decay-corrected). PET imaging demonstrated rapid hepatic uptake with a peak standardized uptake value (SUV) of 8.6 ± 0.8 at 20 min post-injection. The tracer exhibited prompt biliary excretion as demonstrated by a gallbladder SUV of 22.3 ± 1.4 at 45 min post-injection. Time–activity curves confirmed hepatic clearance similar to unlabeled ICG. At 4 h PI, the SUVs of selected organs were: liver 4.7 ± 0.5; lungs 0.15 ± 0.02; small intestine 3.68 ± 0.76; spleen 2.25 ± 0.88; large intestine 4.9 ± 1.7. Renal uptake and clearance was minimal. The whole blood SUV at 1 and 4 h post-injection was 0.47 ± 0.04 and 0.20 ± 0.02, respectively. No overt adverse effects were observed during the 4-h study period.

Conclusions

This study presents [¹⁸F]SFB-ICG as a novel PET tracer for real-time, quantitative assessment of liver function and biliary clearance in vivo. The tracer exhibits favorable pharmacokinetics, high liver specificity, and excellent correlation with established hepatobiliary physiology. Thus, ¹⁸F-SFB-ICG represents a lead compound that warrants further development—including yield optimization, stability and toxicity characterization, and evaluation in animal models of liver disease—for potential applications in hepatic functional imaging, surgical planning, characterization of liver masses, and assessment of biliary pathology.