I-123 SALMON-CALCITONIN, AN IMAGING AGENT FOR CALCITONIN RECEPTORS - SYNTHESIS, BIODISTRIBUTION, METABOLISM AND DOSIMETRY IN HUMANS

Calcitonin is used to reduce high serum calcium levels in patients wit h malignancy, and as therapy for osteoporosis and Paget's disease. Rec eptors for the peptide have been identified in some human cancer cells including those of lung, breast, bone, prostate, and medullary carcin oma of the thyroid, suggesting that an imaging agent for the receptors might be useful in nuclear oncology. A modified chloramine-T method w as used to label a pharmaceutical form of salmon calcitonin (SCT) with iodine-123. Labelling can be performed within 5 min including purific ation, resulting in >95% radiochemical purity and 70% yield. Digestion analysis shows labelling with two iodine atoms on the tyrosine residu e. A Chinese hamster ovary cell-based assay showed that the receptor b inding and activation were not impaired by the labelling. Biodistribut ion in mice was similar to that of commercially available mono-iodinat d I-125-labelled SCT, kidney being the principal target organ. Evaluat ion in three patients previously diagnosed as having Pager's disease ( injected with 37 MBq [I-123]diiodotyrosyl(22)-SCT, containing less tha n 4 IU hormone, imaged dynamically up to 0.5 h and at intervals up to 24 h) shows early uptake in liver, kidney and sites of known Paget's d isease but not in normal bone, and later uptake in thyroid and stomach . Blood clearance was fitted to a biexponential with half-lives of 3.4 -7.4 min and 3-34 h. Radiation dosimetry was estimated using MIRDOSE 3 . The highest doses (mean mGy/MBq) were to thyroid (6.8x10(-1)) and ki dney (6.0x10(-2)), with a whole-body dose 3.0x10(-2). High performance liquid chromatography analysis revealed that urinary radioactivity wa s mostly in the form of iodide and diiodotyrosine within minutes of in jection, indicating rapid in vivo breakdown. In summary, [I-123]diiodo tyrosyl(22)-SCT binds to calcitonin receptors and can image sites of P aget's disease but its imaging potential is not optimal because of rap id breakdown and clearance from target tissues, and an alternative rad iolabelling approach is required.