In vivo distribution

The combination of a PET camera and small cyclotron faciUty provides ready access to the abiUty to image the in vivo distribution of an enormous variety of molecules. The importance of this technique to research is substantial. 

Zhang L, He T, Talal A, Wang G, Frankel SS, Ho DD (1998) In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors CXCR4, CCR3, and CCR5. J Virol 72(6) 5035-5045... 

The pyridinium portion of the previously mentioned partially saturated quinolizinium derivative 74 was reduced by sodium borohydride to yield compound 75, which was employed as a precursor to a radiolabeled methyl ether as a probe for the in vivo distribution of quinolizinium prodrugs (Equation 2) <2001BML519>. 

LS and CLS are solid microparticles with a mean diameter usually between 0.2 and 500 pm, composed of a solid hydrophobic fat matrix in which (in the case of LS) the bioactive compound or compounds are dissolved or dispersed. Because of their large range in particle size, LS can be administered by different routes, such as orally, subcutaneously, intramuscularly, or topically, or they can be used for cell encapsulation, thus allowing them to be proposed for treatment of a number of diseases [26-28], The in vivo distribution of LS demonstrated a high affinity to vascular wells (including capillaries), to inflamed tissues, and to granulocytes [29,30],... 

R. H. Muller, Colloidal Carriers for Controlled Drug Delivery and Targeting Modification, Characterisation and In Vivo Distribution. CRC Press, Stuttgart, 1991. 

In recent years, significant progress has been made in developing prodrug approaches to improve the water solubility, membrane permeability, in vivo distribution, and stability of peptides [193-197]. 

Scintigraphic imaging is a noninvasive imaging technique commonly applied in nuclear medicine. Radiolabeled compounds (called radiopharmaceuticals or radiotracers) are administered intravenously to patients for diagnostic or, in certain cases, therapeutic purposes. The in vivo distribution can provide important physiological information about tissue function. 

Melan and Sluder (6) showed that localizations of soluble proteins in cells can differ markedly from in vivo distributions depending on the fixa-tion/permeabilization regime chosen. Figure 1 (reproduced from 6) shows an... 

The in vivo distribution of rifamide has been studied in dogs and rats [407]. Following intravenous injection by far the highest concentrations of the drug were found in bile and urine a fairly uniform distribution in most other tissues was noted with the exception of brain where the concentration was negligible. In the exudate of rat granuloma pouch high antibiotic concentrations occurred. 

Jain, L., Vidyasagar, D., Xanthou, M., Ghai, V., Shimada, S., and Blend, M. (1989). In vivo distribution of human milk leucocytes after ingestion by newborn baboons. Arch. Dis. Child 64, 930-933. 

Dash, P.R., Read, M.L., Barrett, L.B., Wolfert, M.A., Seymour, L.W. (1999). Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery. Gene Then, 6, 643-650. 

Raman spectroscopy has been successfully used to detect nanomolar concentrations of biologically relevant molecules, to distinguish between structurally similar peptides (e.g. aEp3 and a5pi integrins [22]) and also to detect peptide S-nitrosylation and phosphorylation [23, 24]. Raman spectroscopy has been used to determine the functionalisation of carbon nanotubes and other particles with bioactive peptides (e.g. RGD), whereby their biofunctionalisation has enabled their accumulation at specific sites (e.g. tumours) within small animal models [25]. Furthermore, the in vivo distribution and... 

The Gd3+ chelates used as CAs are administered into the body, and accordingly the requirements for their clinical use are very rigorous. The most important conditions to be met are the lack of toxicity, rapid excretion, high water solubility, a high relaxation effect, high thermodynamic and kinetic stabilities and specific in vivo distribution [2]. 

Tissue uptake clearance is a useful parameter to characterize the in vivo distribution properties of a drag since it is independent of the drag concentration in plasma. However, when the tissue uptake process depends on the drag concentration in plasma and follows non-linear kinetics, the calculated CZapp i represents an average value of its time-dependent clearance for the overall experimental period (Nishikawa et al., 1992). 

Zhang XX, Cui CC, Xu XG, Hu XS, Fang WH, Kuang BJ. In vivo distribution of c-myc antisense oligonucleotides local delivered by gelatin-coated platinum-iridium stent in rabbits and its effect on apoptosis. Chin MedJ (Engl) 2004 I 17(2) 258-263. 

Tissue cross-reactivity studies, although burdensome, provide a rational in vitro assay to determine the range and intensity of distribution of potential epitopes reactive with a monoclonal antibody test article prior to its administration to humans. In addition, cross-reactivity studies provide a useful tool to identify animal species for safety assessment. The cross-reactivity profiles of different species can be compared to the profiles obtained in human tissues. The predictive value of the assay lies in incorporating the characteristics of the monoclonal antibody (isotype, subtype, and other molecular modifications) with the biological activity of the molecule itself, and the potential in vivo distribution of it. 

Graham MJ, Crooke ST, Monteith DK, Cooper SR, Lemonidis KM, Stecker KK, Martin MJ, Crooke RM. In vivo distribution and metabolism of a phosphorothioate oligonucleotide within rat liver after intravenous administration. J Pharmacol Exp Therapeut 1998 286(l) 447-58. 

---