title: Old tracer for a new purpose: potential role for 99mTc-2-Methoxyisobutylisonitrile (99mTc-MIBI) in renal transplant care.
abstract: OBJECTIVE
  Calcineurin inhibitors are substrates for P-glycoprotein (P-gp), the expression of which is associated with ABCB1 C3435T polymorphism. Individual P-gp response to calcineurin inhibitor may be linked to nephrotoxicity or rejection. Tc-2-Methoxyisobutylisonitrile (Tc-MIBI) is also a P-gp substrate. The aim of this study, therefore, was to determine Tc-MIBI organ kinetics and compare them with ABCB1 genotype with a view to replacing Tc-mercaptoacetyltriglycine (Tc-MAG3) with Tc-MIBI in renal transplant care.
  
  
  METHODS
  Thirty prospective donors (13 male) were imaged for 20 min after administration of Tc-MIBI (400 MBq) intravenously. Posterior images of the abdomen were acquired at 30 and 120 min. Organ 30 min/peak count rate ratios and exponential two-point (30-120 min) rate constants (k, min) were calculated. Nineteen donors were genotyped for C3435T (exon 26), G2677T (exon 21), C1236T (exon 12), and G1199A (exon 11) ABCB1 polymorphisms using a PCR-based technique.
  
  
  RESULTS
  Tc-MIBI and Tc-MAG3 gave similar perfusion images. Although their patterns of renal elimination were different, differential renal function was not significantly different. There was a negative trend between the hepatic 30 min/peak ratio and C3435T genotype (CC: 0.8374 ± 0.0502; TC: 0.6806 ± 0.1300; TT: 0.6919 ± 0.1506; P=0.083). Renal k showed a negative trend with C3435T (CC: 0.0021 ± 0.0020; TC: 0.0037 ± 0.0013; TT: 0.0040 ± 0.0012 min; P=0.087) but with no other genotypes. There were no significant sex-related differences in Tc-MIBI kinetics.
  
  
  CONCLUSIONS
  Tc-MIBI can replace Tc-MAG3 for pretransplant workup. The ABCB1 C3435T polymorphism may influence Tc-MIBI kinetics and thus have a role in renal transplant care. Further prospective trials are required to establish the full potential of Tc-MIBI in renal transplant management.
authors.affiliation: aDepartment of Nuclear Medicine bSussex Kidney Unit cClinical Investigation and Research Unit, Brighton and Sussex University Hospitals NHS Trust dBrighton Sussex Medical School, Brighton, UK eDepartment of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria, Australia fInstitute of Nuclear Medicine, University College London, London, UK.
authors.forename: Sabina
authors.initials: S
authors.lastname: Dizdarevic
authors.forename: Mark
authors.initials: M
authors.lastname: Aplin
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Newport
authors.forename: Nicola
authors.initials: N
authors.lastname: Ryan
authors.forename: Stephen
authors.initials: S
authors.lastname: Holt
authors.forename: Stephanie
authors.initials: S
authors.lastname: Goubet
authors.forename: Lawrence
authors.initials: L
authors.lastname: Goldberg
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Miles
authors.forename: A Michael
authors.initials: AM
authors.lastname: Peters
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging; D016030:Kidney Transplantation / Q000379:methods*; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012727:Sex Characteristics; D013154:Spleen / Q000000981:diagnostic imaging; D017263:Technetium Tc 99m Mertiatide; D017256:Technetium Tc 99m Sestamibi
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D019275:Radiopharmaceuticals; D017263:Technetium Tc 99m Mertiatide; D017256:Technetium Tc 99m Sestamibi