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

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Abstract
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.

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