Expression of a New Cellular Protein by Monocytoid B-Lymphocytes Differentiated from the Acute Lymphoblastic Leukemia Cell Line (REH)

In an attempt to identify differentiation-related changes in cellular proteins, the common acute lymphoblastic leukemia (ALL) cell line, REH, was studied. REH cells were cultured in either the absence or presence of 12-0-tetradecanoylphorbol-13-acetate (TPA). Changes in surface phenotype were analyzed using monoclonal antibodies and flow cytometry. Cellular proteins were analyzed with two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of [³H]leucine and [³²P]orthophosphate labeled cells. Immunophenotype and 2D-PAGE studies were replicated three times on untreated (control) and TPA-treated cells on day 5. Immunophenotypic analysis showed that TPA induced further differentiation of REH cells along the B-cell lineage as indicated by significant decrease in the expression of CD10, induction of CD11c and increase in the expression of CD22. 2D-PAGE of [³H]leucine but not the [³²P]orthophosphate showed that TPA induced the expression of a unique protein. The apparent relative molecular mass (Mr) of the resolved protein was ~23 kd with a ~6.2 isoelectric point (PI). Based on the morphologic and phenotypic findings, our data suggest that the new protein (p23-6.2) and the quantitative changes in protein synthesis induced by TPA are differentiation-related. Our study also indicates that 2D-PAGE analysis is a sensitive and complementary tool to phenotypic markers in the study of differentiation of malignant B-cells.     

Investigation of In vitro PDT Activities and In vivo Biopotential of Zinc Phthalocyanines Using 131I Radioisotope

Novel octylthio‐containing asymmetrically substituted Zn(II) phthalocyanine (Zn(II)Pc1) and a symmetric derivative (Zn(II)Pc2) have been prepared to investigate the biological potential and ability to photosensitize singlet oxygen for photodynamic therapy applications. In this study, the singlet oxygen generation potential and in vitro photodynamic activities of these compounds have been tested. Both ZnPcs reveal to be very efficient singlet oxygen generators and promising PSs for PDT applications. In vitro PDT activities of the compounds were evaluated in EMT‐6 murine mammary carcinoma and HeLa human cervix carcinoma cell lines. Moreover, Zn(II)Pc1 displayed the phototoxic effects in the mammary cancer cell line (6.25 μm concentration at 30 J/cm² light dose and 12.5 μm concentration at 20 J/cm² light dose), while Zn(II)Pc2 did not show any phototoxic effects both in two cell lines. Zn(II)Pcs were radiolabeled with ¹³¹I in high yields. Biodistribution studies revealed that the radiolabeled Zn(II)Pc1 showed significant uptake in l. intestine, pancreas, brain, and ovary, while Zn(II)Pc2 has significant uptake in ovary and pancreas in normal rats. Hence, these Pcs derivatives could be promising candidate for tumor nuclear imaging.     

Dendrimer-based contrast agents for PET imaging

Abstract

Positron emission tomography (PET) imaging offers physiological and biological information through the in vivo distribution of PET agents for disease diagnosis, therapy monitoring and prognosis evaluation. Due to the unique structural characteristics allowing for facile modification of targeting ligands and radionuclides, dendrimers can be served as a versatile scaffold to build up various PET imaging agents, and significant breakthroughs have been made in this field over the past decades. This review focuses on the recent advances in dendrimer-based contrast agents for PET imaging of cancer, cardiovascular and other diseases. In particular, radiolabeling strategies for different PET isotopes are described in detail. Several challenges involved in clinical translation of radiolabeled dendrimers are also discussed.     

Novel 64Cu-Labeled CUDC-101 for in Vivo PET Imaging of Histone Deacetylases

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Fusarinine C,a novel siderophore‐based bifunctional chelator for radiolabeling with Gallium‐68

Fusarinine C (FSC), a siderophore‐based chelator coupled with the model peptide c(RGDfK) (FSC(succ‐RGD)₃), revealed excellent targeting properties in vivo using positron emission tomography (PET). Here, we report the details of radiolabeling conditions and specific activity as well as selectivity for ⁶⁸Ga. ⁶⁸Ga labeling of FSC(succ‐RGD)₃ was optimized regarding peptide concentration, pH, temperature, reaction time, and buffer system. Specific activity (SA) of [⁶⁸Ga]FSC(succ‐RGD)₃ was compared with ⁶⁸Ga‐1,4,7‐triazacyclononane, 1‐glutaric acid‐4,7 acetic acid RGD ([⁶⁸Ga]NODAGA‐RGD). Stability was evaluated in 1000‐fold ethylenediaminetetraacetic acid (EDTA) solution (pH 7) and phosphate‐buffered saline (PBS). Metal competition tests (Fe, Cu, Zn, Al, and Ni) were carried out using [⁶⁸Ga]‐triacetylfusarinine C. High radiochemical yield was achieved within 5 min at room temperature, in particular allowing labeling with ⁶⁸Ga up to pH 8 with excellent stability in 1000‐fold EDTA solution and PBS. The 10‐fold to 20‐fold lower concentrations of FSC(succ‐RGD)₃ led to the same radiochemical yield compared with [⁶⁸Ga]NODAGA‐RGD with SA up to 1.8 TBq/µmol. Metal competition tests showed high selective binding of ⁶⁸Ga to FSC. FSC is a multivalent siderophore‐based bifunctional chelator allowing fast and highly selective labeling with ⁶⁸Ga in a wide pH range and results in stable complexes with high SA. Thus it is exceptionally well suited for the development of new ⁶⁸Ga‐tracers for in vivo molecular imaging with PET.     

Stable and high‐yielding intrinsic 59Fe‐radiolabeling of the intravenous iron preparations Monofer and Cosmofer

Commercial iron supplements Monofer^® and Cosmofer^® were intrinsically radiolabeled with ⁵⁹Fe for the purpose of tracing iron absorption in vivo. Optimized procedures aimed at introducing ⁵⁹Fe into the macromolecular construct in a form that was as chemically equivalent to the matrix iron as possible. This was determined by challenging the labeled constructs with diethylenetriaminepentaacetic acid (DTPA) followed by separation by size‐exclusion and measurements of radioactivity and iron in the eluted fractions. The final procedures were simple and involved heating aqueous dispersions of the supplements in the presence of [⁵⁹Fe]FeCl₃ for 24 h at 95 °C for Monofer, and 85 °C for Cosmofer, resulting in radiochemical yields greater than 94%. High performance size exclusion chromatography, UV‐VIS spectroscopy, and dynamic light scattering were used to show that the supplements remained unchanged after radiolabeling, underscoring the applicability of the methodology for radiolabeling commercial iron preparations.