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

✍ Scribed by Wout A.P. Breeman; Leo J. Hofland; Marion de Jong; Bert F. Bernard; Ananth Sinivasan; Dik J. Kwekkeboom; Theo J. Visser; Eric P. Krenning

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 183 KB
• Volume: 81
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990517)81:4<658::aid-ijc24>3.0.co;2-p

✦ Synopsis

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-Tyr 6 ]BN(6-13)NHEt (Et‫؍‬ethyl), [DTPA-Tyr 5 ,D-Phe 6 ]BN(5-13)NHEt, [DTPA-D-Phe 6 ,Leu 13 ⌿Phe 14 ]-BN(6-14), [DTPA-Tyr 5 ,D-Phe 6 ,Leu 13 ⌿Phe 14 ]BN(5-14), [DTPA-Pro 1 ,Tyr 4 ]BN and [DTPA-Pro 1 ,Tyr 4 ,Nle 14 ]BN, were synthesized and studied for their binding characteristics to the BN receptor on 7315b rat pituitary tumour cell membranes in competition with [ 125 I-Tyr 4 ]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 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-Tyr 5 ,D-Phe 6 ]BN(5-13)NHEt and the agonist [DTPA-Pro 1 ,Tyr 4 ]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-Pro 1 ,Tyr 4 ]BN showed much higher specific uptake in BN receptor-positive tissues and tumour than the antagonist [ 111 In-DTPA-Tyr 5 ,D-Phe 6 ]BN(5-13)NHEt, with concordant target to background ratios. We conclude that [ 111 In-DTPA-Pro 1 ,Tyr 4 ]BN has promising characteristics for applications in nuclear medicine.