Pre-clinical evaluation of [111In-DTPA-Pro1, Tyr4]bombesin, a new radioligand for bombesin-receptor scintigraphy
✍ Scribed by Wout A.P. Breeman; Marion De Jong; Bert F. Bernard; Dik J. Kwekkeboom; Ananth Srinivasan; Marcel E. van der Pluijm; Leo J. Hofland; Theo J. Visser; Eric P. Krenning
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 203 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 expressed in a variety of tumours, including lung, breast, prostate and pancreas. 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 IC 50 of 8 nM. The 111 In-labelled analogue was found to bind with high affinity to rat BNR in vitro and in vivo. The radioligand is internalized by BNR-expressing cells, in contrast to DTPA-conjugated BN antagonists. Therefore, we further studied the biodistribution of i.v. injected [ 111 In-DTPA-Pro 1 ,Tyr 4 ]BN in rats. High and specific uptake was found in tissues of the gastrointestinal tract, notably pancreas. Uptake of radioactivity was blocked by pre-or co-injection of 100 g [Tyr 4 ]BN, but not when this was administered 30 min after the radioligand. This suggests BNR-mediated internalization of the radioligand within 30 min. The percentage injected dose (ID) taken up by BNRpositive tissues was a bell-shaped function of the amount (0.01-0.1 g) of injected ligand. Next to the pancreas, highest uptake was observed in the kidneys, which was not blocked by excess [Tyr 4 ]BN. Dynamic gamma camera studies showed rapid clearance of radioactivity from the blood compartment. Urinary excretion amounted to about 35% ID after 1 hr and to 70% ID after 24 hr, with a total body retention of 10% ID. Specific uptake was found in the BNR-positive CA20948 pancreas tumour and CC531 colon carcinoma in tumourbearing rats. The CA20948 tumour, inoculated in the hindleg, was also visualized scintigraphically. [ 111 In-DTPA-Pro 1 , Tyr 4 ]BN appears to be a promising radioligand for scintigraphy of BNR-expressing tumours.