Aim: 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. 99mTc-2-Methoxyisobutylisonitrile (99mTc-MIBI) is also a P-gp substrate. The aim of this study, therefore, was to determine 99mTc-MIBI organ kinetics and compare them with ABCB1 genotype with a view to replacing 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) with 99mTc-MIBI in renal transplant care.
Methods: Thirty prospective donors (13 male) were imaged for 20 min after administration of 99mTc-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−1) 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: 99mTc-MIBI and 99mTc-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−1; P=0.087) but with no other genotypes. There were no significant sex-related differences in 99mTc-MIBI kinetics.
Conclusion: 99mTc-MIBI can replace 99mTc-MAG3 for pretransplant workup. The ABCB1 C3435T polymorphism may influence 99mTc-MIBI kinetics and thus have a role in renal transplant care. Further prospective trials are required to establish the full potential of 99mTc-MIBI in renal transplant management.
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
Correspondence to Sabina Dizdarevic, MD, MSc, FRCP, Department of Nuclear Medicine, Brighton & Sussex University Hospitals NHS Trust, Eastern Road, Brighton, East Sussex BN2 5BE, UK Tel: +44 1273 696 955 x3689; fax: +44 1273 664 923; e-mail: firstname.lastname@example.org
Received April 8, 2014
Accepted June 6, 2014