Are GRP-receptors present in the human pancreas?

Abstract

1607

Objectives: Radiolabelled Bombesin (BN) analogs are successfully being used to visualise Gastrin Releasing Peptide (GRP) receptor-expressing tumors, like prostate and breast tumors. These analogs have potential for radionuclide therapy in patients. However, there is an ongoing discussion as to the presence of GRP receptors in the human pancreas. Accumulation of radiolabelled BN analogs might limit the use in receptor-targeted radionuclide therapy. Although in vivo uptake of BN analogs in the human pancreas has been reported, the presence of GRP receptors could not be confirmed by in vitro autoradiography. In this study we used two bombesin analogs: ¹¹¹In-[DTPA-Pro¹, Tyr⁴]Bombesin (¹¹¹In-MP2248), an analog that showed clear pancreatic uptake in earlier patient studies, and ^99mTc-[(N₄-Bzlg)⁰-D-Phe⁶, Leu-NHEt¹³, des-Met¹⁴]Bombesin(6-14) (^99mTc-Demobesin 1). Reubi et al. (Eur. J. Nucl. Med., 2003) reported a very high selectivity of this latter analog for GRP receptors as compared to other known human bombesin receptors.

Methods: Four patients underwent scintigraphy after injection of 210 MBq (3 μg) ¹¹¹In-MP2248 and 130 MBq (3 μg and in 1 patient 12 μg) ^99mTc- Demobesin 1 (separate sessions). Planar images were made using a dual-headed camera at 3 and 24 h after injection. Additionally, in 2 patients also dynamic series were made directly after injection and spot views were acquired at 45 min pi. Acquisition time for Demobesin 1 at 24 h pi. was 30 min, for all other spot views it was 15 min.

Results: Clear uptake of ¹¹¹In-MP2248 in the pancreatic region of all patients was again noticed. Also, there was clear uptake of the GRP receptor selective ^99mTc-Demobesin 1 in the pancreas. Both analogs showed increasing pancreatic activity in the first 10 min. and clear visualisation of the pancreas at 45 min pi. At 3 h pi. activity of ^99mTc-Demobesin 1 in the pancreas decreased, whereas the amount of radioactivity after ¹¹¹In-MP2248 remained more stable. At 24 h pi. ^99mTc-Demobesin 1 was no longer visualised in the pancreas, while ¹¹¹In-MP2248 uptake was still apparent.

Conclusions: Given the very rapid and clear uptake of the GRP receptor-selective analog ^99mTc-Demobesin 1 in the pancreas, the results may suggest that GRP-receptors are present in the human pancreas. Regardless of whether the uptake is GRP-receptor specific or not, these observations might be of importance for future use of radiolabeled bombesin analogs for therapy.