Fig 1.
Number of differentially regulated transcripts.
Number of differentially regulated transcripts in (a) kidney cortex and (b) kidney medulla 4, 8 and 12 months after administration of 30–150 MBq 177Lu-octreotate. Distribution of up- and down-regulated transcripts is indicated with positive and negative numbers, respectively
Table 1.
Differentially regulated transcripts which have previously been proposed as biomarkers for kidney injury, radiation induced damage, and radiation biodosimetry [33–36]. The log2ratio is shown for each gene.
Fig 2.
Recurrently regulated transcripts in kidney cortex.
Gene expression patterns for differentially regulated transcripts with recurrent expression at one or more time points in kidney cortex 4, 8 or 12 months after administration of 30–150 MBq 177Lu-octreotate. * Statistically significant regulation (see Materials and Methods)
Fig 3.
Recurrently regulated transcripts in kidney medulla.
Gene expression patterns for differentially regulated transcripts with recurrent expression at one or more time points in kidney medulla 4, 8, or 12 months after administration of 30–150 MBq 177Lu-octreotate. * Statistically significant regulation (see Materials and Methods)
Table 2.
Top upstream regulators of transcripts with recurrent expression (cf. Figs 2 and 3) in kidney cortex and medulla
Fig 4.
Kidney histology in control animals as well as in animals where no histological changes were seen at (a) 10x magnification and (b) 40x magnification. The glomeruli are normocellular, with open capillary loops. No signs of segmentalization, necrosis or sclerosis were seen. The tubular, interstitial, and vascular compartments were all without histological changes, no signs of necrosis or inflammation were noted. The histological changes associated with the group receiving 150 MBq at 12 months are shown at (c) 10x magnification and (d) 40x magnification. The changes were localized to the glomeruli. These displayed focal signs of segmental sclerosis and segmentalization of the glomeruli, indicating cellular injury to the mesangium and glomerular capillaries. Edemtatous closure of the capillary loops was noted. Furthermore, the nuclei displayed degenerative changes with polymorphism and nuclear fragmentation, potentially indicating detrimental radiation effects. In a fraction of the glomeruli, signs of segmental fibrinoid necrosis were seen, again underscoring acute injury to the glomeruli. Tubules, interstitium and vasculature showed no signs of injury in these tissues. Staining by standard hematoxylin and eosin. The glomeruli are depicted with”G” and the distal tubules with”DT”.
Fig 5.
Results from 99mTc-DTPA scintigraphy performed 4, 8, and 12 months after administration of 0, 30, 90 or 150 MBq 177Lu-octreotate. The kidney uptake is presented as percent of injected activity. Error bars represent SEM and * indicates statistically significant difference compared with controls (p <0.05), and at 4 months the ** indicates statistical significance for the 90 and 150 MBq groups.
Fig 6.
Urinary bladder content following 99mTc-DTPA administration.
Urinary bladder content at 27.5 min after 99mTc-DTPA administration. Scintigraphy was performed at 4, 8, and 12 months after administration of 30–150 MBq 177Lu-octreotate. Kidney uptake is presented as percent of injected activity. Error bars represent SEM
Fig 7.
Results from 99mTc-DMSA scintigraphy performed 4, 8, and 12 months after 177Lu-octreotate administration. The kidney uptake is presented as percent of injected activity normalized to controls. Error bars represent SEM and * indicates statistically significant difference compared with controls (p<0.05)
Table 3.
Overview of the results concerning body weight, blood cell count, urea and creatinine blood levels, 99mTc-DTPA and 99mTc-DMSA scintigraphy, and histology. The results are presented as test divided by control (given as percent)