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

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‐expre...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 1999-05, Vol.81 (4), p.658-665
Main Authors: Breeman, Wout A.P., Hofland, Leo J., de Jong, Marion, Bernard, Bert F., Sinivasan, Ananth, Kwekkeboom, Dik J., Visser, Theo J., Krenning, Eric P.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biological and medical sciences
Bombesin - analogs & derivatives
Bombesin - chemical synthesis
Bombesin - chemistry
Bombesin - pharmacokinetics
Female
Indium Radioisotopes - pharmacokinetics
Indium Radioisotopes - therapeutic use
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Miscellaneous. Technology
Pentetic Acid
Pituitary Neoplasms - diagnostic imaging
Pituitary Neoplasms - pathology
Pituitary Neoplasms - radiotherapy
Prolactin - analysis
Radiation therapy and radiosensitizing agent
Radionuclide Imaging
Radionuclide investigations
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - pharmacokinetics
Rats
Rats, Inbred BUF
Receptors, Bombesin - analysis
Receptors, Bombesin - metabolism
Tissue Distribution
Treatment with physical agents
Treatment. General aspects
Tumors
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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,Leu13ΨPhe14]‐BN(6–14), [DTPA‐Tyr5,D‐Phe6,Leu13ΨPhe14]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 characterisitics. Internalization of selected 111In‐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 111In‐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 111In‐labelled agonist, but not the antagonist, was internalized by the BN receptor‐positive tumour cells. Consonant with this observation, the agonist [111In‐DTPA‐Pro1,Tyr4]BN showed much higher specific uptake in BN receptor‐positive tissues and tumour than the antagonist [111In‐DTPA‐Tyr5,D‐Phe6]BN(5–13)NHEt, with concordant target to background ratios. We conclude that [111In‐DTPA‐Pro1,Tyr4]BN has promising characteristics for applications in nuclear medicine. Int. J. Cancer 81:658–665, 1999. © 1999 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/(SICI)1097-0215(19990517)81:4<658::AID-IJC24>3.0.CO;2-P