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Abstract: Porphyrin-containing polyaspartamide ligands (APTSPP–PHEA–DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4′-aminophenyl)-10,15,20-tris(4′-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP–PHEA–DTPA–Gd). Experimental data of 1H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP–PHEA–DTPA–Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd–DTPA. Moreover, APTSPP–PHEA–DTPA–Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. [Copyright &y& Elsevier]

Tumor-selective macromolecular ligands containing 5-(p-Carbonyloxyphenyl)-10,15,20-triphenylporphyrin (HPTP) moiety (PHEA-DTPAHPTP and PAEA-DTPA-HPTP) were prepared by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(p-hydroxylphenyl)-10,15, 20-triphenylporphyrin (HPTP) as the tumor-selective group in poly [α,β-(N(2-hydroxyethyl)-L-aspartamide)] (PHEA) and poly-[α,β-(N-(2-aminoethyl)-Laspartamide)] (PAEA). These ligands were further complexed with gadolinium chloride to form two tumor-selective macromolecular MRI contrast agents PHEA-Gd-DTPA-HPTP and PAEA-Gd-DTPA-HPTP. Relaxivity studies showed that both the polyaspartamide-gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of tumors in mice indicated that these two polyaspartamide MRI contrast agents containing 5-(p-Carbonlyoxyphenyl)-10,15,20-triphenylporphyrin moiety can significantly enhance the contrast MRIs of Hepatoma (H[sub 22]) and Ehrlich ascites carcinoma after injection and are taken up selectively by these cancers in mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dual-modal MRI/FI gents were made by incorporation of Gd-DTPA and RhB to Laminin/Fibronectin receptor-targeting sequences. • Dual-modal MRI/FI gents possessed low cell cytotoxicity, high relativity, good tumor-targeting and good fluorescent property. • Dual-modal MRI/FI gents showed good performance of combined MRI with FI and improve the accuracy of tumor detection. Dual-modal magnetic resonance/fluorescent imaging (MRI/FI) attracts more and more attentions in diagnosis of tumors. A corresponding dual-modal imaging agent with sufficient tumor sensitivity and specificity should be matched to improve imaging quality. Tripeptide (RGD) and pentapeptide (YIGSR) were selected as the tumor-targeting groups and attached to gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and rhodamine B (RhB), and then make two novel polypeptide-based derivatives (RGD-Gd-DTPA-RhB and YIGSR-Gd-DTPA-RhB), respectively. These derivatives were further characterized and their properties, such as cell uptake, cell cytotoxicity, MRI and FI assay, were measured. YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB had high relaxivity, good tumor-targeting property, low cell cytotoxicity and good red FI in B16F10 melanoma cells. Moreover, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB possessed high uptake to B16F10 melanoma, and then achieve highly enhanced FI and MRI of tumors in mice for a prolonged time. Therefore, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB can be applied as the potential agents for tumor targeted MRI/FI in vivo. [ABSTRACT FROM AUTHOR]

Diethylenetriaminepentaacetic di(L-dopa ethyl ester) ligand (DTPA-2LDEE) was synthesized by reaction between diethylenetriaminepentaacetic dianhydride (DTPAA) and L-dopa ethyl ester (LDEE). This ligand reacted with gadolinium chloride and sodium pertechnetate to make the corresponding neutral gadolinium complex Gd-DTPA-2LDEE and technetium-99m-labeled complex99mTc-DTPA-2LDEE, respectively. The ligand and complexes were characterized and their propertiesin vitroandin vivowere also evaluated. Gd-DTPA-2LDEE possessed higher relaxation effectiveness and lower cytotoxicity to human hepatoma HepG-2 cells than Gd-DTPA.99mTc-DTPA-2LDEE had enhanced single-photon emission computed tomography (SPECT) signal enhancements of the kidneys in rats and provided longer duration time than that of99mTc-DTPA. Therefore,99mTc-DTPA-2LDEE can be selectively excreted by the kidneys and used as a potential radioactive probe in SPECT. [ABSTRACT FROM AUTHOR]