Image-derived input function from the vena cava for 18F-FDG PET studies in rats and mice

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Rodent Imaging

Background:

• Quantitative (18)F-FDG PET studies in rodents are crucial for preclinical research.
• Measuring the arterial input function (AIF) is a significant challenge due to small blood volumes and difficulties in repetitive blood sampling.
• Accurate AIF is essential for reliable quantification of metabolic rates, such as cerebral metabolic rate of glucose (CMRGlc).

Purpose of the Study:

• To develop and validate a minimally invasive method for determining the (18)F-FDG input function in rats and mice using image-derived input function (IDIF) from the vena cava.
• To assess the accuracy of CMRGlc quantification using this IDIF method compared to traditional approaches.
• To evaluate the impact of dispersion correction and blood sampling on CMRGlc measurements.

Main Methods:

• Utilized a high-resolution small-animal PET scanner to extract IDIF from the vena cava in Sprague-Dawley rats and C57BL/6 mice.
• Validated the rat IDIF against an external microvolumetric blood counter and manual blood samples.
• Applied tracer bolus dispersion correction and explored the impact of IDIF extraction methods on CMRGlc using simulation studies and the Patlak approach.

Main Results:

• The vena cava IDIF provided robust CMRGlc determination using compartmental modeling or the Patlak approach, with minimal underestimation (7% ± 16%) even without dispersion correction or blood sampling.
• In mice, the IDIF method yielded a cortical CMRGlc of 0.22 ± 0.10 μmol/g/min, consistent with previous studies.
• In rats, dispersion correction and a single blood sample improved CMRGlc accuracy, reducing underestimation to 6% ± 7%.

Conclusions:

• The time-activity curve derived from the vena cava serves as a minimally invasive and effective alternative for measuring the (18)F-FDG input function in rodents.
• This approach circumvents the complications associated with repetitive arterial blood sampling.
• The method enables accurate quantification of CMRGlc in small animals, facilitating preclinical PET research.