title: Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney.
abstract: OBJECTIVE
  The radioligand 11C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of 11C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method in pigs with the goal of translation into human studies.
  
  
  METHODS
  The experimental animals were injected with [11C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function.
  
  
  RESULTS
  In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio=1±0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method.
  
  
  CONCLUSIONS
  The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of 11C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Benjamin M W
authors.initials: BM
authors.lastname: Tsui
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Melin
authors.initials: M
authors.lastname: Vranesic
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lodge
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Nedim C M
authors.initials: NC
authors.lastname: Gulaldi
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism; D019540:Area Under Curve; D001774:Blood Chemical Analysis; D001810:Blood Volume; D001811:Blood Volume Determination; D002138:Calibration; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D003198:Computer Simulation; D004912:Erythrocytes / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000493:pharmacokinetics*; D007668:Kidney / Q000033:anatomy & histology / Q000000981:diagnostic imaging* / Q000378:metabolism; D018810:Magnetic Resonance Angiography; D008954:Models, Biological; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D034421:Sus scrofa; D013777:Tetrazoles / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: C493912:2-butyl-5-methoxymethyl-6-(1-oxopyridin-2-yl)-3-((2'-(1H-tetrazol-5-yl)bipohenyl-4-yl)methyl)-3H-imidazo(4,5-b)pyridine; D002250:Carbon Radioisotopes; D007093:Imidazoles; D019275:Radiopharmaceuticals; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles