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Objective To evaluate 99Tcm-Arg-Glu-Ser (99Tcm-RES) as a potential tumor imaging agent. Methods RES was synthesized using solid phase peptide synthesis. The optimal labeling conditions of RES were determined under different reagents and reacting temperatures using SnC12 as reducing agent.The biodistribution of 99Tcm-RES was studied in nude mice bearing human lung cancer A549. Results The radiochemical purity of 99Tcm-RES was up to 85% and the radiochemical purity was 75% ever after 6 h at room temperature. The tumor uptake of 99Tcm-RES was obvious and the radioactivity ratios of tumor/blood,tumor/heart, tumor/liver, tumor/lung, tumor/spleen and tumor/muscle were 5.31, 1.88, 1.57, 3.58,4. 16 and 5.92, respectively at 6 h after 99Tcm-RES injection. Gamma camera imaging showed that tumor uptake of 99Tcm-RES was negative in rabbits with inflammatory mass but positive in those bearing tumor.The radioactivity ratio of tumor/inflammation was 3.12 at 6 h after injection. Conclusion 99Tcm-RES might possibly become a potential tumor imaging agent.
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Objective To investigate the uptake of 99Tcm-hydrazinonicotinamide-D-alanine-D-alanine-alanine-proline-arginine-proline-glycine (HYNIC-A(D) A(D) APRPG) in rabbit models of inflammation and VX2 tumor xenografted, so as to evaluate its use as a new tracer for tumor angiogenesis. Methods Ten rabbit models of xenoplanted VX2 tumor and inflammation were randomly divided into two groups which were injected with different injected tracers, 99Tcm-HYNIC-A(D) A (D)APRPG 99Tcm-RGD, followed by serial Gamma images at various time points. The first group underwent 18F-FDG PET ahead of 99Tcm-HYNICA(D)A (D) APRPG SPECT. Analysis of variance and t-test were performed with SPSS 10.0. Results 99TcmHYNIC-A(D) A (D)APRPG scan showed negative uptake at inflammation focus but positive uptake at tumor. Pathological examination confirmed high 99Tcm-HYNIC-A(D)A(D) APRPG accumulation in tumor cells, with the highest tumor/inflammation ratio (3.25 ±0. 171) at 2 h post-injection, which was significantly higher than that of 99Tcm-RGD (2.37 ± 0.076) (F = 15. 63, P<0. 01). The tumor/inflammation ratios of 99Tcm-HYNIC-A(D)A(D)APRPG, 99Tcm-RGD, 18F-FDG were significantly different at 0.5, 1,2,3, 6 h (F = 13. 83～26. 41; t = 23.84, 12.75; all P<0. 01). Conclusion 99Tcm-HYNIC-A (D) A (D)APRPG can be used as a potential tracer for tumor angiogenesis.
ABSTRACT
<p><b>BACKGROUND</b>Screening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo.</p><p><b>METHODS</b>The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium (V) oxo core [TcO(3+)] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 (99m)Tc tripeptoid complexes. The radiocombinatorial screening (RCS) in vivo was carried out on SD rats and A549 tumour bearing mice.</p><p><b>RESULTS</b>Signals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, (99m)Tc RPA, (99m)Tc VIG and (99m)Tc RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of (99m)Tc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of (99m)Tc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. (99m)Tc DSG was finally identified the most promising agent for renal function studies.</p><p><b>CONCLUSIONS</b>RCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.</p>