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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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PET scans from four of eight corresponding VCaP-bearing mice: a scans after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq); b scans after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq). Using the OSEM3D/MAP algorithm the last ten frames of each scan were summed for image reconstruction. Arrows indicate tumour location
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Fig2: PET scans from four of eight corresponding VCaP-bearing mice: a scans after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq); b scans after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq). Using the OSEM3D/MAP algorithm the last ten frames of each scan were summed for image reconstruction. Arrows indicate tumour location

Mentions: Using 68Ga-AMBA, all VCaP and PC-3 tumours were clearly visualized by PET. High uptake was seen in tumour tissue as well as in GRPR-positive pancreas tissue and in organs responsible for clearance (kidneys and bladder), while uptake in background organs was low (Fig. 2a). When performing PET scans using 18F-FCH it was more difficult to distinguish VCaP and PC-3 tumours from background tissues due to the relatively low tumour uptake and high uptake in surrounding background organs (Fig. 2b). In 20% of all 18F-FCH scans it was not possible to determine the tumour from background due to the poor contrast.Fig. 2


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)

PET scans from four of eight corresponding VCaP-bearing mice: a scans after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq); b scans after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq). Using the OSEM3D/MAP algorithm the last ten frames of each scan were summed for image reconstruction. Arrows indicate tumour location
© Copyright Policy
Related In: Results  -  Collection

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

Fig2: PET scans from four of eight corresponding VCaP-bearing mice: a scans after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq); b scans after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq). Using the OSEM3D/MAP algorithm the last ten frames of each scan were summed for image reconstruction. Arrows indicate tumour location
Mentions: Using 68Ga-AMBA, all VCaP and PC-3 tumours were clearly visualized by PET. High uptake was seen in tumour tissue as well as in GRPR-positive pancreas tissue and in organs responsible for clearance (kidneys and bladder), while uptake in background organs was low (Fig. 2a). When performing PET scans using 18F-FCH it was more difficult to distinguish VCaP and PC-3 tumours from background tissues due to the relatively low tumour uptake and high uptake in surrounding background organs (Fig. 2b). In 20% of all 18F-FCH scans it was not possible to determine the tumour from background due to the poor contrast.Fig. 2

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