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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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Uptakes in different tissues over time: a VCaP tumour (y-axis in two segments); b kidney; c bladder. Black solid lines show median uptake and black dashed lines IQR after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq, N = 8). Grey lines show median uptake and IQR after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq, N = 8)
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Fig3: Uptakes in different tissues over time: a VCaP tumour (y-axis in two segments); b kidney; c bladder. Black solid lines show median uptake and black dashed lines IQR after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq, N = 8). Grey lines show median uptake and IQR after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq, N = 8)

Mentions: Dynamic tracer uptake in VCaP tumour, bladder and kidney over time is shown in Fig. 3. Tumour uptake of both tracers was fast, reaching peak values within 3–5 min. 68Ga-AMBA uptake reached a plateau phase at approximately 20 min after injection, while 18F-FCH uptake reached a plateau in less than 10 min (Fig. 3a). We used the average uptake in the plateau phase to calculate the total tumour uptake. In VCaP tumours, uptake was 6.7 ± 1.4%ID/g (N = 8) for 68Ga-AMBA, and only 1.6 ± 0.5%ID/g (N = 8) for 18F-FCH. This difference was highly significant (p <0.001). Similarly, for PC-3 tumours, uptake was 9.2 ± 1.1%ID/g (N = 3) for 68Ga-AMBA and 1.2 ± 0.3%ID/g (N = 3) for 18F-FCH. Renal clearance of 68Ga-AMBA gradually progressed over time resulting in accumulation of bladder radioactivity at 10 min after injection (Fig. 3b). Renal clearance of 18F-FCH occurred immediately after injection resulting in increased bladder radioactivity immediately after injection (Fig. 3c).Fig. 3


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)

Uptakes in different tissues over time: a VCaP tumour (y-axis in two segments); b kidney; c bladder. Black solid lines show median uptake and black dashed lines IQR after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq, N = 8). Grey lines show median uptake and IQR after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq, N = 8)
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Related In: Results  -  Collection

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Fig3: Uptakes in different tissues over time: a VCaP tumour (y-axis in two segments); b kidney; c bladder. Black solid lines show median uptake and black dashed lines IQR after tail vein injection of 68Ga-AMBA (300 pmol, 1.5–0.5 MBq, N = 8). Grey lines show median uptake and IQR after tail vein injection of 18F-FCH (100 μl, 8.1–1.2 MBq, N = 8)
Mentions: Dynamic tracer uptake in VCaP tumour, bladder and kidney over time is shown in Fig. 3. Tumour uptake of both tracers was fast, reaching peak values within 3–5 min. 68Ga-AMBA uptake reached a plateau phase at approximately 20 min after injection, while 18F-FCH uptake reached a plateau in less than 10 min (Fig. 3a). We used the average uptake in the plateau phase to calculate the total tumour uptake. In VCaP tumours, uptake was 6.7 ± 1.4%ID/g (N = 8) for 68Ga-AMBA, and only 1.6 ± 0.5%ID/g (N = 8) for 18F-FCH. This difference was highly significant (p <0.001). Similarly, for PC-3 tumours, uptake was 9.2 ± 1.1%ID/g (N = 3) for 68Ga-AMBA and 1.2 ± 0.3%ID/g (N = 3) for 18F-FCH. Renal clearance of 68Ga-AMBA gradually progressed over time resulting in accumulation of bladder radioactivity at 10 min after injection (Fig. 3b). Renal clearance of 18F-FCH occurred immediately after injection resulting in increased bladder radioactivity immediately after injection (Fig. 3c).Fig. 3

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