In vivo model of drug-induced valvular heart disease in rats: pergolide-induced valvular heart disease demonstrated with echocardiography and correlation with pathology

The aim of this study was the comparison of the tumour uptake and the long-term retention of [I-123]-2-I-L-phenylalanine and [I-123]-2-I-D-phenylalanine with those of [I-123]-2-I-L-tyrosine and [I-123]-2-I-D-tyrosine in RIM rhabdomyosarcoma tumour-bearing rats. The biodistribution of the radioactivity as a function of time in RIM tumour-bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting.[I-123]-2-iodo-L-phenylalanine, [I-123]-2-iodo-D-phenylalaine, [I-123] -2-I-L-tyrosine showed a considerable turnout uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L- and D-[I-123]-2-I-tyrosine were cleared for a large part from the tumours and the body. [I-123]-2-I-L-Phe and [I-123]-2-I-D-Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour-to-background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the RIM-bearing Wag/Rij rat model only [I-123]-2-1-L-phenylalanine and [I-123]-2-I-D-phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers.