Labelling of peptides with 188Re/99Tcm and monoclonal antibodies with 90Y/111In

Radiopharmaceuticals derived from oncophilic small molecular weight peptides have attracted attention as vehicles to deliver radioactivity to tumour cells for external imaging and targeted radiotherapy. The aim of the present work was the study of labelling of biomolecules, specifically peptides or antibodies with beta emitter radioisotopes such as 188Re. The direct labelling of two somatostatin analogues, Octreotide and Lanreotide, with 188Re and 99Tcm was done, including optimization of this labelling and biological studies. The radiochemical yield was greater than 95%. 188Re-lanreotide gave better radiochemical yields than 188Reoctreotide and was stable for 24 h. Similar results were obtained with 99Tcm-octreotide and 99Tcm-lanreotide. However, a difference in mass ratio (reducing agent/peptide) was observed, being much greater with 188Re. 99Tcm-labelled peptides were localized in the gastrointestinal tract or in the kidneys and blood clearance wasn't observed during 6 h. Biodistribution of 188Re-peptides showed similar results as obtained with 99Tcm-peptides. The indirect method was used to label DOTATOC with 188Re and 99Tcm and competition binding assays were done with the labelled product. The results showed a radiochemical yield in the range of 92 to 94%. We observed better uptake of 99Tcm-DOTATOC in AR42J cell membranes than in brain cortex membranes. The results obtained with 188Re-DOTATOC were inconclusive. Labelling of monoclonal antibody for prostate cancer cells (J591) with 111In and 90Y, and immunoreactivity of the product was also studied. The radiolabelling yield for J591 with 111In and 90Y was higher than 90%. An average of five DOTA molecules could be randomly conjugated to J591, yielding specific activities of 280 MBq 111In/mg DOTA-J591 and 360 MBq 90Y/mg DOTA-J591, with little apparent loss of immunoreactivity. (author)