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Selection of Radiolabeled Gastrin Analogs for Peptide Receptor–Targeted Radionuclide Therapy

Stephen J. Mather1, Andrew J. McKenzie2, Jane K. Sosabowski1, Teresa M. Morris2, David Ellison1 and Susan A. Watson2

1 Department of Nuclear Medicine, St. Bartholomew's Hospital, London, United Kingdom; and 2 Academic Unit of Cancer Studies, University of Nottingham, Nottingham, United Kingdom


Figure 1
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  		FIGURE 1.  Biodistribution of H2-Met in AR42J-bearing nude mice, between 1 and 72 h after intravenous administration. Greatest initial uptake is observed in tumor and kidney but washout from kidney is faster than that from tumor. Four-hour blocking data indicate biodistribution when 100 µg of unlabeled peptide were coadministered with radiolabeled peptide. Significant blocking effect (P < 0.0005) is seen in blood, tumor, and stomach, but no other organs. int = intestine.

 

Figure 2
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  		FIGURE 2.  Effect of peptide dose on biodistribution. Results are expressed as percentage change in uptake compared with that obtained with "standard" dose of 0.2 µg. No significant dose effect was observed in any tissue other than tumor and stomach. Increasing the dose above 0.2 µg reduced uptake in both tissues. Decreasing the dose had no effect on tumor uptake but increased uptake in the stomach.

 

Figure 3
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  		FIGURE 3.  Fused SPECT/CT image shows biodistribution of 111In-H2-Met in AR42J-bearing nude mouse, 4 h after intravenous injection. Heterogeneous uptake can be observed in tumor with little uptake in central organs.

 

Figure 4
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  		FIGURE 4.  HPLC chromatograms of 111In-H2-Met prepared with and without addition of antioxidant MTG, where trace a contained no MTG (resulting in 12.3% oxidized peptide, Rt = 19.6 min) and trace b contained 0.04 mg MTG (resulting in 5.9% oxidized peptide, Rt = 19.2 min).

 




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