Optimization of a neurotensin(8-13) analogue for radioiodination

2-123I-phenylacetyl-NT(8-13)-OH (1) and 4-HO-2-123I-phenylacetyl-[Phe11]-NT(8-13)-OH (2) were developed as potential SPECT tracers for NT-receptor expressing tumors. The precursor compounds showed high affinity for NT-receptors on bulbus olfactorius membranes of rodent (Ki in the Mn range). (1) Was obtained by Cu1 assisted non-isotopic exchange on 1 mg of the 2-Br-phenylacetyl analogue, with a labeling yield of 70%. (2) Was obtained by direct electrophilic substitution during 5 min at Rt using Iodogen on 0.1 mg 4-HO-phenylacetyl-[Phe11]-NT(8-13)-OH with a yield >98%. The second method allows a two component kit application. In vivo in the rat fast degradation (t1/2: 1.5 min) was observed coupled to high long-acting liver uptake. This is probably caused by radioiodo-phenylacetyl-Arg, a compound that mimics MIBG. 4-HO-phenylacetyl-[Lys8Y(CH2NH)Arg9]-[tLeu12]-NT(8-13)-OH, a double stabilized NT(8-13) analogue of type (2), from which high in vivo stability is expected, was synthesised.