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In this study, [111 In]In-DOTA-PR81 was developed, and its preliminary preclinical qualifications were assessed for single photon emission computed tomography (SPECT) imaging of breast cancer. DOTA-NHS-ester was practiced and successively purified by molecular filtration. The chelate:mAb ratio was determined by spectrophotometry. DOTA-PR81 was radiolabeled with In-111 and its radiochemical yield, in vitro stability, in vitro internalization, and immunoreactivity tests were performed. SPECT imaging and tissue counting were applied to evaluate the tissue distribution of [111 In]In-DOTA-hIgG and [111 In]In-DOTA-PR81 in BALB/c mice bearing breast tumors. The radiochemical yield of [111 In]In-DOTA-PR81 complex was >95.0 ± 0.5% (ITLC), and the specific activity was 170 ± 44 MBq/mg. Conjugation reaction resulted in the average number of chelators attached to a mAb (c/a) of 3.4 ± 0.3:1. The radioimmunoconjugate showed immunoreactivity towards MCF7 cell line and MUC1 antigen while its significant in vitro and in vivo stability were investigated over 48 h, respectively (93.0 ± 1.2% in phosphate-buffered saline (PBS) and 84.0 ± 1.3% in human serum). The peak concentration of internalized activity of [111 In]In-DOTA-PR81 was between 4 to 6 h. In comparison with control probes, the complex was accumulated with high specificity and sensitivity at the tumor site. Achieved results indicated that [111 In]In-DOTA-PR81 could be contemplated as an appropriate radiotracer for prognostic imaging of antigens in oncology.

A new class of δ opioid antagonists was recently discovered in which the sequence Tyr-Tic was used as a message domain. The substitution of Tyr1 by Dmt enhanced the δ selectivity and antagonist activity. The excellent properties of these ligands stimulated us to prepare the corresponding tritiated derivatives. Peptides containing Tic at position 2 undergo spontaneous diketopiperazine formation in some solvents, with a reduction in opioid activity. To avoid this side-reaction we synthesised the N,N-dimethylated analogue (N,N(Me)2-Dmt-Tic-OH), which was found to be stable. On the basis of this result, we prepared diiodinated analogues of H-Dmt-Tic-OH and N,N(Me)2-Dmt-Tic-OH to undergo catalytic dehalotritiation. Products of high specific radioactivity were obtained: 44.67 Ci/mmol for [3H]Dmt-Tic-OH and 59.88 Ci/mmol for [3H]N,N(Me)2-Dmt-Tic-OH. Copyright © 1998 John Wiley & Sons, Ltd.