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Retrograde transport of radiolabelled botulinum neurotoxin type A to the CNS after intradetrusor injection in rats
Author(s) -
Papagiannopoulou Dionysia,
Vardouli Lina,
Dimitriadis Fotios,
Apostolidis Apostolos
Publication year - 2016
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.13163
Subject(s) - chemistry , neurotoxin , incubation , high performance liquid chromatography , nuclear medicine , chromatography , biochemistry , medicine
Objective To investigate the potential distribution of radiolabelled botulinum neurotoxin type A (Bo NT /A) in the CNS after bladder injection in normal rats, by using the gamma‐emitting radionuclide technetium‐99 m ( 99m Tc). Materials and Methods Bo NT /A was radiolabelled by pretreatment with 2‐iminothiolane and incubation with 99m Tc‐gluconate. The labelled toxin 99m Tc‐Bo NT /A was purified using size exclusion HPLC . Twenty‐four female Wistar rats were evenly injected in the bladder wall with either 99m Tc‐ΒοΝΤ/Α ( n = 12) or free 99m Tc ( n = 12). Four rats from each group were killed at 1, 3 and 6 h after injection, respectively. The bladder, L6‐S1 spinal cord segment and L6‐S1 dorsal root ganglia ( DRG ) were harvested and their radioactivity counted in a gamma scintillation detector. Results were calculated as % injected dose (I.D.) per gram of tissue. The paired t ‐test was used for comparison of means of 99m Tc‐ΒοΝΤ/Α radioactivity vs free 99m Tc in the tissues of interest. Results Radiolabelled Bo NT /A had a high radiochemical stability of 70% after 24 h. Gradual accumulation of 99m Tc‐ΒοΝΤ/Α was observed in the DRG up to 6 h after injection ( P = 0.04 and P = 0.029 compared with 1 h and 3 h, respectively), while no accumulation was detected for free 99m Tc. Consequently, 99m Tc‐ΒοΝΤ/Α radioactivity in the DRG was higher than free 99m Tc radioactivity (3.18 ± 0.67% I.D./g vs 0.19 ± 0.10% I.D./g [ P = 0.002] 6 h after injection). Values for 99m Tc‐ΒοΝΤ/Α radioactivity in the spinal cord were higher than those for free 99m Tc, but not significantly. The bladder retained higher dosages of 99m Tc‐ΒοΝΤ/Α than free 99m Tc at all time points. Conclusions Significant accumulation of the radiolabelled toxin in the lumbosacral DRG , together with a less significant uptake in the respective spinal cord segment as opposed to free radioactivity provide first evidence of the retrograde transport of Bo NT /A to the CNS after bladder injection in rats.