title: Preclinical characterization of 18F-MAA, a novel PET surrogate of 99mTc-MAA.
abstract: BACKGROUND
  (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) scintigraphy scan is routinely performed for lung perfusion imaging and for the assessment of in vivo distribution of (90)Y-labeled SIR-Spheres prior to selective internal radiation treatment for hepatocellular carcinoma. Positron emission tomography (PET) imaging is superior to gamma scintigraphy in terms of sensitivity, spatial resolution and accuracy of quantification. This study reported that (18)F-labeled macroaggregated albumin ((18)F-MAA) is an ideal PET imaging surrogate for (99m)Tc-MAA.
  
  
  METHODS
  (18)F-MAA was prepared from the commercial MAA kit via a one-step conjugation with N-succinimidyl 4-(18)F-fluorobenzoate ((18)F-SFB). The biodistribution study and microPET/microSPECT imaging were conducted in normal SD rats after intravenous injection of (18)F-MAA/(99m)Tc-MAA. A comparison study of these two radiotracers was performed after co-injection via the intrahepatic arterial in a N1S1 hepatoma-bearing SD rat model.
  
  
  RESULTS
  The optimal condition for (18)F-MAA preparation is coupling MAA (0.5mg) with (18)F-SFB at 45°C for 5 min in a phosphate buffer of pH 8.5. (18)F-MAA was prepared in 60 min with high radiochemical yield (30%-35%) and high radiochemical purity (>95%). The in vivo distribution of (18)F-MAA after intravenous injection meets the specifications of MAA depicted in European Pharmacopeia. Our study demonstrated excellent correlation between (18)F-MAA and (99m)Tc-MAA in the regional distribution of tumor, liver and lungs (R(2)=0.965, 0.886 and 0.991, respectively), and also in the tumor-to-liver and tumor-to-lungs ratio (R(2)=0.965 and 0.987, respectively) in a N1S1 hepatoma-bearing SD rat model. The organ uptakes derived from animal PET/CT and SPECT/CT imaging after administration of these two tracers were in accordance with those obtained in the distribution studies.
  
  
  CONCLUSIONS
  Starting from commercial MAA kit, an efficient preparation of (18)F-MAA was successfully established. Highly correlated, almost parallel, regional distribution of (18)F-MAA and (99m)Tc-MAA in both normal rats and hepatoma-bearing rats was observed. The findings, taken together, demonstrate that (18)F-MAA is an ideal surrogate for (99m)Tc-MAA for clinical PET applications.
authors: Department of Biomedical imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan.
authors: Shih-Yen
authors: SY
authors: Wu
authors: Jia-Wei
authors: JW
authors: Kuo
authors: Tien-Kuei
authors: TK
authors: Chang
authors: Ren-Shen
authors: RS
authors: Liu
authors: Rheun-Chuan
authors: RC
authors: Lee
authors: Shyh-Jen
authors: SJ
authors: Wang
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Hsin-Ell
authors: HE
authors: Wang
mesh_terms: D000818:Animals; D001565:Benzoates / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D013668:Technetium Tc 99m Aggregated Albumin / Q000737:chemistry / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D001565:Benzoates; D005462:Fluorine Radioisotopes; D013438:Sulfhydryl Compounds; D013668:Technetium Tc 99m Aggregated Albumin; C082426:technetium Tc99m-mercaptoacetyl albumin; C022893:4-fluorobenzoic acid