Introduction: Medullary thyroid carcinomas (MTC) reveal overexpression of several peptide receptors particularly of gastrin and cholecystokinin 2 (CCK2). Experimental studies of various CCK-2/gastrin analogues found that a C-terminal, 8-aminoacid peptide, _DGlu-octagastrin, has optimal properties. Thus, the aim of our studies was to prepare ^99mTc-labelled HYNIC-octagastrin, to evaluate its biologic tolerance in animals and introduce for scintigraphy in patients with MTC.
Material and methods: HYNIC-_DGlu-octagastrin was from piCHEM (Graz, Austria), ^99mTc generator from Amersham (Health), other reagents were purchased from Sigma. Labelling of the peptide was performed in phosphate buffer of pH 6.0 for 10 minutes at 100^oC using EDDA and tricine as coligands.
Results: The labeling yields were high (above 95%); the specific activity amounted to 1200 to 1430 μCi/μg. Radiochemical purity on SepPak cartridge and ITLC ranged from 94 to 98%. No adverse effects were observed in mice after administration of 10 to 50 times greater doses that those used in patients. Clinical studies comprised 20 patients with MTC and high serum calcitonin. ^99mTc-EDDA/HYNIC-^DGlu-octagastrin, 500 to 700 MBq, was administered iv and whole body scintigraphy was performed using a double head gamma-camera (Varicam, Elscint) 2 and 4 hours later. Increased accumulation of the tracer in foci of MTC and its metastases was found in 8 patients.
Conclusions: Scintigraphy with a new gastrin analogue (^DGlu-octagastrin) makes it possible to detect MTC with overexpression of CCK-2/gastrin receptors and to select patients for receptor-mediated radiopeptide therapy using DOTA-gastrin analogues labelled with ¹⁷⁷Lu and ⁹⁰Y.