Pre-clinical evaluation of [In-111-DTPA-Pro(1), Tyr(4)] bombesin, a new radioligand for bombesin-receptor scintigraphy

Bombesin (BN) is a 14-amino-acid neuropeptide with a high affinity for the gastrin-releasing peptide receptor. This receptor has been found to be expr essed in a variety of tumours, including lung, breast, prostate and pancrea s. A newly synthesized BN analogue, [DTPA-Pro(1),Tyr(4)]BN, was shown to be a high-affinity BN-receptor (BNR) agonist, stimulating prolactin secretion from 7315b cells with an IC50 Of 8 nM. The In-111-labelled analogue was fo und to bind with high affinity to rat BNR in vitro and in vivo. The radioli gand is internalized by BNR-expressing cells, in contrast to DTPA-conjugate d BN antagonists. Therefore, we further studied the biodistribution of i.v. injected [In-111-DTPA-Pro(1) ,Tyr(4)]BN in rats. High and specific uptake was found in tissues of the gastrointestinal tract, notably pancreas. Uptak e of radioactivity was blocked by pre- or co-injection of 100 lug [Tyr(4)]B N, but not when this was administered 30 min after the radioligand. This su ggests BNR-mediated internalization of the radioligand within 30 min. The p ercentage injected dose (ID) taken up by BNR-positive tissues was a bell-sh aped function of the amount (0.01-0.1 mu g) Of injected ligand. Next to the pancreas, highest uptake was observed in the kidneys, which was not blocke d by excess [Tyr(4)]BN. Dynamic gamma camera studies showed rapid clearance of radioactivity from the blood compartment. Urinary excretion amounted to about 35% la after I hr and to 70% ID after 24 hr, with a total body reten tion of 10% ID. Specific uptake was found in the BNR-positive CA20948 pancr eas tumour and CC531 colon carcinoma in tumour-bearing rats. The CA20948 tu mour, inoculated in the hindleg, was also visualized scintigraphically. [In -111-DTPA-Pro(1), Tyr(4)]BN appears to be a promising radioligand for scint igraphy of BNR-expressing tumours. (C) 1999 Wiley-Liss, Inc.