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Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts.

Schroeder RP, van Weerden WM, Krenning EP, Bangma CH, Berndsen S, Grievink-de Ligt CH, Groen HC, Reneman S, de Blois E, Breeman WA, de Jong M - Eur. J. Nucl. Med. Mol. Imaging (2011)

Bottom Line: All tumours were clearly visualized using (68)Ga-AMBA. (18)F-FCH showed significantly less contrast due to poor tumour-to-background ratios.Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 ± 4.8%ID/g (N = 8) for (68)Ga-AMBA and 2.1 ± 0.4%ID/g (N = 8) for (18)F-FCH.These results suggest that peptide receptor-based targeting using the bombesin analogue AMBA is superior to metabolism-based targeting using choline for scintigraphy of PC.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. r.schroeder@erasmusmc.nl

ABSTRACT

Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the (68)Ga-labelled bombesin analogue AMBA with metabolism-based targeting using (18)F-methylcholine ((18)F-FCH) in nude mice bearing human prostate VCaP xenografts.

Methods: PET and biodistribution studies were performed with both (68)Ga-AMBA and (18)F-FCH in all VCaP tumour-bearing mice, with PC-3 tumour-bearing mice as reference. Scanning started immediately after injection. Dynamic PET scans were reconstructed and analysed quantitatively. Biodistribution of tracers and tissue uptake was expressed as percent of injected dose per gram tissue (%ID/g).

Results: All tumours were clearly visualized using (68)Ga-AMBA. (18)F-FCH showed significantly less contrast due to poor tumour-to-background ratios. Quantitative PET analyses showed fast tumour uptake and high retention for both tracers. VCaP tumour uptake values determined from PET at steady-state were 6.7 ± 1.4%ID/g (20-30 min after injection, N = 8) for (68)Ga-AMBA and 1.6 ± 0.5%ID/g (10-20 min after injection, N = 8) for (18)F-FCH, which were significantly different (p <0.001). The results in PC-3 tumour-bearing mice were comparable. Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 ± 4.8%ID/g (N = 8) for (68)Ga-AMBA and 2.1 ± 0.4%ID/g (N = 8) for (18)F-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for (68)Ga-AMBA than for (18)F-FCH.

Conclusion: Tumour uptake of (68)Ga-AMBA was higher while overall background activity was lower than observed for (18)F-FCH in the same PC-bearing mice. These results suggest that peptide receptor-based targeting using the bombesin analogue AMBA is superior to metabolism-based targeting using choline for scintigraphy of PC.

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Structural formulas of BN, 68Ga-AMBA and 18F-FCH
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Fig1: Structural formulas of BN, 68Ga-AMBA and 18F-FCH

Mentions: Choline is an essential nutrient that serves as a precursor for the synthesis of phosphatidylcholine, a major constituent of the cell membrane [20]. NMR spectroscopy has demonstrated higher concentrations of phosphocholine in human tumour tissues and in normal cells when stimulated by (mitogenic) growth factors [21, 22]. In PC the cellular uptake and phosphorylation of choline is often increased compared to normal prostate epithelial and stromal cells [23, 24]. Most PC imaging studies are PET scans using 11C-labelled choline [5, 15, 25, 26]. Since 11C has a relatively short half-life of 20 min, the use of this radionuclide is limited to centres with on-site cyclotrons. This drawback has led to the development of choline derivatives including N-[18F]-fluoromethyl-N-(2-hydroxyethyl)-N,N-dimethylammonium (18F-FCH) with a radionuclide half-life of 110 min. The biodistribution of 18F-FCH is comparable to that of 11C-choline, although 18F-FCH shows higher renal activity [27]. The structures of BN, 68Ga-AMBA and 18F-FCH are shown in Fig. 1.Fig. 1


Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts.

Schroeder RP, van Weerden WM, Krenning EP, Bangma CH, Berndsen S, Grievink-de Ligt CH, Groen HC, Reneman S, de Blois E, Breeman WA, de Jong M - Eur. J. Nucl. Med. Mol. Imaging (2011)

Structural formulas of BN, 68Ga-AMBA and 18F-FCH
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104004&req=5

Fig1: Structural formulas of BN, 68Ga-AMBA and 18F-FCH
Mentions: Choline is an essential nutrient that serves as a precursor for the synthesis of phosphatidylcholine, a major constituent of the cell membrane [20]. NMR spectroscopy has demonstrated higher concentrations of phosphocholine in human tumour tissues and in normal cells when stimulated by (mitogenic) growth factors [21, 22]. In PC the cellular uptake and phosphorylation of choline is often increased compared to normal prostate epithelial and stromal cells [23, 24]. Most PC imaging studies are PET scans using 11C-labelled choline [5, 15, 25, 26]. Since 11C has a relatively short half-life of 20 min, the use of this radionuclide is limited to centres with on-site cyclotrons. This drawback has led to the development of choline derivatives including N-[18F]-fluoromethyl-N-(2-hydroxyethyl)-N,N-dimethylammonium (18F-FCH) with a radionuclide half-life of 110 min. The biodistribution of 18F-FCH is comparable to that of 11C-choline, although 18F-FCH shows higher renal activity [27]. The structures of BN, 68Ga-AMBA and 18F-FCH are shown in Fig. 1.Fig. 1

Bottom Line: All tumours were clearly visualized using (68)Ga-AMBA. (18)F-FCH showed significantly less contrast due to poor tumour-to-background ratios.Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 ± 4.8%ID/g (N = 8) for (68)Ga-AMBA and 2.1 ± 0.4%ID/g (N = 8) for (18)F-FCH.These results suggest that peptide receptor-based targeting using the bombesin analogue AMBA is superior to metabolism-based targeting using choline for scintigraphy of PC.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. r.schroeder@erasmusmc.nl

ABSTRACT

Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the (68)Ga-labelled bombesin analogue AMBA with metabolism-based targeting using (18)F-methylcholine ((18)F-FCH) in nude mice bearing human prostate VCaP xenografts.

Methods: PET and biodistribution studies were performed with both (68)Ga-AMBA and (18)F-FCH in all VCaP tumour-bearing mice, with PC-3 tumour-bearing mice as reference. Scanning started immediately after injection. Dynamic PET scans were reconstructed and analysed quantitatively. Biodistribution of tracers and tissue uptake was expressed as percent of injected dose per gram tissue (%ID/g).

Results: All tumours were clearly visualized using (68)Ga-AMBA. (18)F-FCH showed significantly less contrast due to poor tumour-to-background ratios. Quantitative PET analyses showed fast tumour uptake and high retention for both tracers. VCaP tumour uptake values determined from PET at steady-state were 6.7 ± 1.4%ID/g (20-30 min after injection, N = 8) for (68)Ga-AMBA and 1.6 ± 0.5%ID/g (10-20 min after injection, N = 8) for (18)F-FCH, which were significantly different (p <0.001). The results in PC-3 tumour-bearing mice were comparable. Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 ± 4.8%ID/g (N = 8) for (68)Ga-AMBA and 2.1 ± 0.4%ID/g (N = 8) for (18)F-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for (68)Ga-AMBA than for (18)F-FCH.

Conclusion: Tumour uptake of (68)Ga-AMBA was higher while overall background activity was lower than observed for (18)F-FCH in the same PC-bearing mice. These results suggest that peptide receptor-based targeting using the bombesin analogue AMBA is superior to metabolism-based targeting using choline for scintigraphy of PC.

Show MeSH
Related in: MedlinePlus