Biodistribution study procedure

DOTATATE) with and lutetium ( Lu). The quality control and purification procedures are also described. Biodistribution studies were performed in normal Swiss mice and in nude mice bearing AR42J tumours. In vitro studies were used to evaluate the affinity of the radiopharmaceuticals for somatostatin receptors in rat brain cortex and tumour cells. Saturation binding and the internalization of the labelled peptides were determined. The frequency of micronuclei in peripheral blood lymphocytes exposed to different radioactive concentrations of [ IJDOTATATE and [ Lu]DOTATATE was evaluated by micronucleus assay. 

In the present study, the methodology used for labelling DOTATATE with and Lu is described, along with the purification and quality control procedures. In vitro methods and in vivo procedures were also applied to elucidate the biodistribution of radiopharmaceuticals and their affinity for somatostatin receptors. 

Only few data are available in the literature that deal with the measurement of Gd in biological fluids and tissues. Some workers used atomic emission spectrometry (AES) for the determination of Gd in tissues [4] after digesting samples with nitric acid. Others used radiolabeled Gd to study the biodistribution of the element [14]. ICP-MS has been used for the determination of Gd in serum and urine. With this method samples are simply diluted in water [16]. To our knowledge the method described by the group of D Haese [28] is the only report that exists on the determination of Gd in biological fluids and tissues by electrothermal AAS (ETAAS). With this procedure the element can be accurately determined in serum, urine, blood, bone, and tissues after extraction into methyl isobutyl ketone followed by reextraction in hydrochloric acid. Atomization of the element for AAS determination is performed from a tantalum boat. 

In biodistribution, metabolic, and pharmacokinetic studies, the radiolabelled tracer is administered to the subject and samples of tissues are subsequently taken to be measured in a scintillation counter in order to quantify the amount of radioactivity present in that sample. For this type of application any of the radionuclides listed in Table 1 may be used. In animal studies the amount of radioactivity which needs to be administered will be determined by the efficiency of the detection rstem and normal radiation safety considerations. For studies in human subjects the radiation dose to the recipient is likely to be paramount. For these reasons iodine-125 will probably be the radionuclide of choice for this type of study and the labelling procedure described above may be used. 

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