Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours

Nucl Med Biol. 1998 Apr;25(3):181-8. doi: 10.1016/s0969-8051(97)00163-7.

Abstract

An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation 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-Phe1 of Tyr3-octreotide. This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiolabelled with 90Y prior to serum stability being evaluated. Receptor binding assays were also performed on the two radioligands using rat cortex membranes. The [90Y]-Bz-DTPA-oct was further evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA-octreotide) bound with a high affinity to SRIF receptors and the 90Y complex was relatively stable in human serum (t1/2 3.8 d for 90Y lost to serum proteins). The second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF receptors, but it demonstrated an even slower loss of 90Y to serum proteins (t1/2 12.1 d). The in vivo evaluation of the more stable [90Y]-Bz-DTPA-oct showed a very rapid and high accumulation in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, and liver, respectively). These tumour/nontumour ratios increased, and were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver). Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand for 90Y radiotherapy of somatostatin receptor-positive tumours and their metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Stability
  • Half-Life
  • Humans
  • Indicators and Reagents
  • Male
  • Octreotide / analogs & derivatives
  • Octreotide / chemical synthesis*
  • Octreotide / pharmacokinetics
  • Octreotide / therapeutic use
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / metabolism*
  • Pentetic Acid / analogs & derivatives
  • Pentetic Acid / chemical synthesis*
  • Pentetic Acid / pharmacokinetics
  • Pentetic Acid / therapeutic use
  • Radioligand Assay
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Rats
  • Rats, Inbred Lew
  • Receptors, Somatostatin / analysis
  • Receptors, Somatostatin / metabolism*
  • Tissue Distribution
  • Yttrium Radioisotopes* / pharmacokinetics
  • Yttrium Radioisotopes* / therapeutic use

Substances

  • Indicators and Reagents
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Yttrium Radioisotopes
  • Pentetic Acid
  • Octreotide