Publications (5)15.74 Total impact
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Article: Iodine-124 as a label for pharmacological PET imaging.
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ABSTRACT: With the growing number of biotechnology products and drug delivery systems entering preclinical and clinical studies, pharmacological imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long physical half-lives. Among the currently available PET positron emitters, ¹²⁴I has the longest physical half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes ¹²⁴I very attractive for pharmacological studies. However, the high energy of the positrons emitted by ¹²⁴I and the presence of single photons in the ¹²⁴I emission can potentially introduce limitations in the quantitative analysis of the images. The objective of this research was to determine whether the use of ¹²⁴I as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resolution, count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with ¹²⁴I, up to 185 MBq/mg. The transaxial and axial spatial resolutions in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was observed up to 44 MBq. Animal studies demonstrated excellent delineation and resolution of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body weight for larger animals, the quality of numerical data was appropriate for PK analysis in all experimental timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that ¹²⁴I is an excellent label for quantitative pharmacological PET imaging studies.Molecular Pharmaceutics 03/2011; 8(3):736-47. · 4.78 Impact Factor -
Article: Iodine-124 as a Label for Pharmacological PET Imaging
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ABSTRACT: With the growing no. of biotechnol. products and drug delivery systems entering preclin. and clin. studies, pharmacol. imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long phys. half-lives. Among the currently available PET positron emitters, 124I has the longest phys. half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes 124I very attractive for pharmacol. studies. However, the high energy of the positrons emitted by 124I and the presence of single photons in the 124I emission can potentially introduce limitations in the quant. anal. of the images. The objective of this research was to det. whether the use of 124I as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resoln., count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with 124I, up to 185 MBq/mg. The transaxial and axial spatial resolns. in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was obsd. up to 44 MBq. Animal studies demonstrated excellent delineation and resoln. of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body wt. for larger animals, the quality of numerical data was appropriate for PK anal. in all exptl. timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that 124I is an excellent label for quant. pharmacol. PET imaging studies. [on SciFinder(R)]Mol. Pharmaceutics. 8(3):736-747. -
Article: Iodine-124 as a Label for Pharmacological PET Imaging
[show abstract] [hide abstract]
ABSTRACT: With the growing no. of biotechnol. products and drug delivery systems entering preclin. and clin. studies, pharmacol. imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long phys. half-lives. Among the currently available PET positron emitters, 124I has the longest phys. half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes 124I very attractive for pharmacol. studies. However, the high energy of the positrons emitted by 124I and the presence of single photons in the 124I emission can potentially introduce limitations in the quant. anal. of the images. The objective of this research was to det. whether the use of 124I as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resoln., count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with 124I, up to 185 MBq/mg. The transaxial and axial spatial resolns. in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was obsd. up to 44 MBq. Animal studies demonstrated excellent delineation and resoln. of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body wt. for larger animals, the quality of numerical data was appropriate for PK anal. in all exptl. timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that 124I is an excellent label for quant. pharmacol. PET imaging studies. [on SciFinder(R)]Mol. Pharmaceutics. 8(3):736-747. -
Article: Fully degradable hydrophilic polyals for protein modification.
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ABSTRACT: Modification of proteins with hydrophilic polymers is an effective strategy for regulation of protein pharmacokinetics. However, conjugates of slowly or non-biodegradable materials, such as poly(ethylene glycol), are known to cause long-lasting cell vacuolization, in particular in renal epithelium. Conjugates of more degradable polymers, e.g., polysaccharides, have a significant risk of immunotoxicity. Polymers that combine complete degradability, long circulation in vivo, and low immuno and chemical toxicity would be most beneficial as protein conjugate components. This study explores new fully biodegradable hydrophilic polymers, hydrophilic polyals. They are nontoxic, stable at physiological conditions, and undergo proton-catalyzed hydrolysis at lysosomal pH. The model enzyme-polyal conjugates were prepared with 61-98% yield using conventional and novel conjugation techniques and retained 90-95% of specific activity. The model conjugates showed a significant prolongation of protein circulation in rodents, with a 5-fold reduction in the renal accumulation. The data suggests that hydrophilic polyals may be useful in designing protein conjugates with improved properties.Biomacromolecules 6(5):2648-58. · 5.48 Impact Factor -
Article: Semisynthetic hydrophilic polyals.
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ABSTRACT: Non-bioadhesive, fully biodegradable soluble polymers would be very instrumental in advanced biomedical applications, such as gene and drug delivery and tissue engineering. However, rational development of such materials is hindered by the complexity of macromolecule interactions with biological milieu. The prevalence of carbohydrates in naturally occurring interface structures suggests an alternative, biomimetic approach. Interface carbohydrates, regardless of their biological function, have common non-signaling substructures (e.g., acetal and ketal groups, secondary and primary alcohols). We hypothesized that hydrophilic polymers (polyals) consisting of acyclic units built of non-signaling carbohydrate substructures would be highly biocompatible and non-bioadhesive, while intrachain acetal or ketal groups would enable nonenzymatic biodegradation upon uptake by cells. Acyclic hydrophilic polyals can be prepared via either polymerization of suitable monomers or lateral cleavage of cyclic polyals (e.g., polysaccharides). In this study, model polyals were produced via lateral cleavage of polyaldoses and polyketoses. Best results were achieved using dextran B-512 as a precursor. The resultant poly[hydroxymethylethylene hydroxymethylformal], in agreement with the hypothesis, demonstrated excellent biological properties and technological flexibility. Materials of this type can potentially have several applications in pharmacology and bioengineering.Biomacromolecules 6(5):2659-70. · 5.48 Impact Factor
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Institutions
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2011
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Massachusetts General Hospital
- Department of Radiology
Boston, MA, USA
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