Evaluation of radiolabelled bombesin analogues for receptor-targeted scintigraphy and radiotherapy

Int J Cancer. 1999 May 17;81(4):658-65. doi: 10.1002/(sici)1097-0215(19990517)81:4<658::aid-ijc24>3.0.co;2-p.


The 14-aminoacid peptide bombesin (BN) has a high affinity for the gastrin-releasing peptide receptor which is expressed by a variety of tumours. Thus, radiometal-labelled DTPA-BN derivatives are potentially useful radioligands for receptor-targeted scintigraphy and radiotherapy of BN receptor-expressing tumours. A number of such DTPA-BN analogues, [DTPA-D-Tyr6]BN(6-13)NHEt (Et=ethyl), [DTPA-Tyr5,D-Phe6]BN(5-13)NHEt, [DTPA-D-Phe6,Leu13psiPhe14]BN(6-14), [DTPA-Tyr5,D-Phe6,Leu13psiPhe14]BN(5-14), [DTPA-Pro1,Tyr4]BN and [DTPA-Pro1,Tyr4,Nle14]BN, were synthesized and studied for their binding characteristics to the BN receptor on 7315b rat pituitary tumour cell membranes in competition with [125I-Tyr4]BN. The effects of the BN analogues were determined on basal and BN-stimulated prolactin secretion by 7315b cells to distinguish between their agonistic and antagonistic characteristics. Internalization of selected (111)In-labelled BN analogues was studied using the BN receptor-positive 7315b pituitary tumour and the CA20948 and AR42J exocrine pancreas tumour cell lines. The tissue distribution of these (111)In-labelled BN analogues was investigated in 7315b tumour-bearing rats. Two DTPA-conjugated analogues, the antagonist [DTPA-Tyr5,D-Phe6]BN(5-13)NHEt and the agonist [DTPA-Pro1,Tyr4]BN showed the highest affinity for the BN receptor on 7315b cell membranes. Despite similar affinity for the BN receptor, the (111)In-labelled agonist, but not the antagonist, was internalized by the BN receptor-positive tumour cells. Consonant with this observation, the agonist [(111)In-DTPA-Pro1,Tyr4]BN showed much higher specific uptake in BN receptor-positive tissues and tumour than the antagonist [(111)In-DTPA-Tyr5,D-Phe6]BN(5-13)NHEt, with concordant target to background ratios. We conclude that [(111)In-DTPA-Pro1,Tyr4]BN has promising characteristics for applications in nuclear medicine.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bombesin / analogs & derivatives*
  • Bombesin / chemical synthesis*
  • Bombesin / chemistry
  • Bombesin / pharmacokinetics
  • Female
  • Indium Radioisotopes / pharmacokinetics
  • Indium Radioisotopes / therapeutic use
  • Pentetic Acid
  • Pituitary Neoplasms / diagnostic imaging*
  • Pituitary Neoplasms / pathology
  • Pituitary Neoplasms / radiotherapy*
  • Prolactin / analysis
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Inbred BUF
  • Receptors, Bombesin / analysis*
  • Receptors, Bombesin / metabolism
  • Tissue Distribution


  • Indium Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Bombesin
  • Pentetic Acid
  • Prolactin
  • Bombesin