HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Daldrup-Link, H. E. Articles by Link, T. M. Search for Related Content PubMed PubMed Citation Articles by Daldrup-Link, H. E. Articles by Link, T. M.

Targeting of Hematopoietic Progenitor Cells with MR Contrast Agents¹

¹ From Dept of Radiology (H.E.D.L., M.S., S.M., E.J.R., T.M.L.), Inst of Pathology (M.R., G.P., U.H., J.S.), Third Clinic of Internal Medicine, Laboratory of Stem Cell Physiology (R.A.J.O., U.K.), Dept Clinical Chemistry and Pathochemistry (H.R.), and National Research Ctr for Environment and Health (U.H.), Technical Univ, Ismaninger Str 22, 81675 Munich, Germany. Received Apr 2, 2002; revision requested Jun 13; final revision received Oct 31; accepted Jan 14, 2003. Supported by German Research Foundation grant DA 529/1-1. Address correspondence to H.E.D.L. (e-mail: daldrup@roe.med.tu-muenchen.de).

View larger version (141K): [in a new window]   Figure 1. Electron microscopic images of hematopoietic progenitor cells. A, Nonlabeled control cell. B-F, Labeled cells are shown with inserts of contrast medium containing cytoplasmatic vesicles (which are not in all cases taken from the section of the image). In B, gadopentetate dimeglumine liposomes (arrow) are clustered within the cytoplasm. In C-F, intracellular accumulations of iron oxides form clusters in secondary lysosomes (arrows). The amount of internalized particles appears to be maximal for magnetic polysaccharide nanoparticles-transferrin (C), followed by ferumoxides (D), and ferumoxtran (E). In F, the relatively small amount of internalized P7228 can be increased substantially by means of transfection with liposomes.

View larger version (28K): [in a new window]   Figure 2. Curve depicts cellular uptake of MR contrast agents with increasing cell number, as quantified with spectrometry for iron oxides (micrograms of iron) and with inductively coupled plasma atomic emission spectrometry for gadopentetate dimeglumine (micrograms of gadolinium). , = gadopentetate dimeglumine liposomes; , = ferumoxides; , = P7228 liposomes; , = P7228; and , = magnetic polysaccharide nanoparticles. Solid keys = cell pellets visible on either T1- or T2-weighted MR images. Open keys = cell pellets that could not be detected at MR imaging.

View larger version (18K): [in a new window]   Figure 3. Validation curves of measurements as a function of contrast agent concentration in 1 mL of DMEM. A, T2* measurements. B, T1 measurements. In A, curve shows increasing concentrations (micrograms of iron) of P7228, as a representative iron oxide contrast agent, displayed against R2*, which was measured with a fast field-echo echo-planar MR imaging sequence. In B, curve shows increasing concentrations (micrograms of gadolinium) of gadopentetate dimeglumine displayed against R1, which was measured with a mixed inversion-recovery SE MR sequence.

View larger version (157K): [in a new window]   Figure 4. Representative MR images of centrifuged cell pellets in test tubes placed in a water bath. Each cell pellet contains 106 cells after exposure to the various contrast agents: SPIO = ferumoxides, Nano-Tf = magnetic polysaccharide nanoparticles-transferrin, USPIO = ferumoxtran, USPIO-Lipos. = P7228 liposomes, Gd-DTPA-Lipos. = gadopentetate dimeglumine liposomes. Each probe was imaged with the following sequences: T1-weighted SE (T1-SE) (500/15), T1-weighted fast field echo (T1-FFE) (25/2.7 with 40° flip angle), T2-weighted SE (T2-SE) (2,500/90), and fast field echo (T2*-FFE) (25/12 with 20° flip angle). Note decreased SI in ferumoxides-labeled cell pellets on T2-weighted images and increased SI in gadopentetate dimeglumine liposomes (Gd-DTPA-Lipos.)-labeled cell pellets on T1-weighted MR images. The supernatant above the cells in the test tubes shows identical SI compared with that of the surrounding water bath.

View larger version (153K): [in a new window]   Figure 5. Follow-up MR images of human hematopoietic progenitor cells in test tubes that were obtained before (pre) and 4 hours, 5 days, and 7 days after labeling with gadopentetate dimeglumine liposomes (Gd-DTPA-Lipos.) or P7228 liposomes (USPIO-Lipos.). Gadolinium-labeled cells show a persistent T1 effect over 7 days, whereas iron oxide-labeled cells show a gradually declining T2 effect. T1-FFE = T1-weighted fast field echo, T2*-FFE = T2*-weighted fast field echo.