SYNTHESIS AND CHARACTERIZATION OF [Y-90] BZ-DTPA-OCT - A YTTRIUM-90-LABELED OCTREOTIDE ANALOG FOR RADIOTHERAPY OF SOMATOSTATIN RECEPTOR-POSITIVE TUMORS

An investigation into the in vitro behaviour of two yttrium-90 labelle d somatostatin analogues was performed. Further in vivo characterisati on was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe(1) of Tyr(3)-octreotide . This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiola belled with Y-90 prior to serum stability being evaluated. Receptor bi nding assays were also performed on the two radioligands using rat cor tex membranes. The [Y-90]-Bz-DTPA-oct was further evaluated in vivo us ing tumour-bearing rats. The first conjugate (DTPA octreotide) bound w ith a high affinity to SRIF receptors and the Y-90 complex was relativ ely stable in human serum (t(1/2) 3.8 d for Y-90 lost to serum protein s). The second conjugate (Bz-DTPA-oct) also exhibited a high binding a ffinity to SRIF receptors, but it demonstrated an even slower loss of Y-90 to serum proteins (t(1/2) 12.1 d). The in aivo evaluation of the more stable [Y-90] Bz-DTPA oct showed a very rapid and high accumulati on in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, an d liver, respectively), These tumour/nontumour ratios increased, and w ere by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and li ver), Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accum ulated in somatostatin receptor-positive tissue. Octadentate Bz DTPA o ct could be ligand for Y-90 radiotherapy of somatostatin receptor-posi tive tumours and their metastases. (C) 1998 Elsevier Science Inc.