Abstract
This study was designed to determine if repeat injections of polyethylene glycol (PEG) coated liposomes in the same animal lead to a change in biodistribution due to a biological response. To evaluate the long- term storage of PEG-liposomes for imaging applications and to remove any concerns of batch variability, one large batch of PEG-liposomes containing glutathione and sucrose was prepared and used for the entire study. On each day that an imaging study was performed, an aliquot of PEG-liposomes were labeled with technetium-99m (99mTc) using hexamethylpropyleneamine oxime. Rabbits (n = 4) were injected with 99mTc-PEG-liposomes (2 ml; 13 mg phospholipid/kg body wt; 2 mCi 99mTc-activity) at 8 days after manufacture and imaged under a gamma camera. Heart-to-lung ratios, heart-to-liver ratios and organ activities were determined by region of interest analysis. Blood samples were collected to generate blood clearance curves. Six weeks later the same rabbits were given a second dose of 99mTc-PEG-liposomes at 50 days after manufacture and imaged as before. A set of new rabbits (n = 3) were also imaged at six weeks using 99mTC-PEG-liposomes in order to differentiate any differences in organ distribution due to storage vs. reinjection. Images acquired for each set of rabbits at 30 minutes demonstrated little change in organ distribution following reinjection. Heart-to-lung ratios decreased from 2.25 ± 0.06 at baseline to 2.05 0.05 on reinjection and 2.10 ± 0.01 upon storage. Heart-to-liver ratios were 1.46 ± 0.06 on reinjection, significantly lower than the ratio of 1.72 ± 0.10 at baseline or 1.68 ± 0.09 upon storage. Circulation half-life of 29 hours did not change within the three groups. Although a slight change in organ biodistribution occurred with storage and reinjection, these effects were minimal and are not likely to affect drug targeting or diagnostic imaging on repeat injection.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 265-281 |
| Number of pages | 17 |
| Journal | Journal of Liposome Research |
| Volume | 8 |
| Issue number | 2 |
| State | Published - 1998 |
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ASJC Scopus subject areas
- Pharmacology
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Repeat injection studies of technetium-99m-labeled PEG-liposomes in the same animal. / Goins, Beth; Phillips, William T; Klipper, Robert.
In: Journal of Liposome Research, Vol. 8, No. 2, 1998, p. 265-281.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Repeat injection studies of technetium-99m-labeled PEG-liposomes in the same animal
AU - Goins, Beth
AU - Phillips, William T
AU - Klipper, Robert
PY - 1998
Y1 - 1998
N2 - This study was designed to determine if repeat injections of polyethylene glycol (PEG) coated liposomes in the same animal lead to a change in biodistribution due to a biological response. To evaluate the long- term storage of PEG-liposomes for imaging applications and to remove any concerns of batch variability, one large batch of PEG-liposomes containing glutathione and sucrose was prepared and used for the entire study. On each day that an imaging study was performed, an aliquot of PEG-liposomes were labeled with technetium-99m (99mTc) using hexamethylpropyleneamine oxime. Rabbits (n = 4) were injected with 99mTc-PEG-liposomes (2 ml; 13 mg phospholipid/kg body wt; 2 mCi 99mTc-activity) at 8 days after manufacture and imaged under a gamma camera. Heart-to-lung ratios, heart-to-liver ratios and organ activities were determined by region of interest analysis. Blood samples were collected to generate blood clearance curves. Six weeks later the same rabbits were given a second dose of 99mTc-PEG-liposomes at 50 days after manufacture and imaged as before. A set of new rabbits (n = 3) were also imaged at six weeks using 99mTC-PEG-liposomes in order to differentiate any differences in organ distribution due to storage vs. reinjection. Images acquired for each set of rabbits at 30 minutes demonstrated little change in organ distribution following reinjection. Heart-to-lung ratios decreased from 2.25 ± 0.06 at baseline to 2.05 0.05 on reinjection and 2.10 ± 0.01 upon storage. Heart-to-liver ratios were 1.46 ± 0.06 on reinjection, significantly lower than the ratio of 1.72 ± 0.10 at baseline or 1.68 ± 0.09 upon storage. Circulation half-life of 29 hours did not change within the three groups. Although a slight change in organ biodistribution occurred with storage and reinjection, these effects were minimal and are not likely to affect drug targeting or diagnostic imaging on repeat injection.
AB - This study was designed to determine if repeat injections of polyethylene glycol (PEG) coated liposomes in the same animal lead to a change in biodistribution due to a biological response. To evaluate the long- term storage of PEG-liposomes for imaging applications and to remove any concerns of batch variability, one large batch of PEG-liposomes containing glutathione and sucrose was prepared and used for the entire study. On each day that an imaging study was performed, an aliquot of PEG-liposomes were labeled with technetium-99m (99mTc) using hexamethylpropyleneamine oxime. Rabbits (n = 4) were injected with 99mTc-PEG-liposomes (2 ml; 13 mg phospholipid/kg body wt; 2 mCi 99mTc-activity) at 8 days after manufacture and imaged under a gamma camera. Heart-to-lung ratios, heart-to-liver ratios and organ activities were determined by region of interest analysis. Blood samples were collected to generate blood clearance curves. Six weeks later the same rabbits were given a second dose of 99mTc-PEG-liposomes at 50 days after manufacture and imaged as before. A set of new rabbits (n = 3) were also imaged at six weeks using 99mTC-PEG-liposomes in order to differentiate any differences in organ distribution due to storage vs. reinjection. Images acquired for each set of rabbits at 30 minutes demonstrated little change in organ distribution following reinjection. Heart-to-lung ratios decreased from 2.25 ± 0.06 at baseline to 2.05 0.05 on reinjection and 2.10 ± 0.01 upon storage. Heart-to-liver ratios were 1.46 ± 0.06 on reinjection, significantly lower than the ratio of 1.72 ± 0.10 at baseline or 1.68 ± 0.09 upon storage. Circulation half-life of 29 hours did not change within the three groups. Although a slight change in organ biodistribution occurred with storage and reinjection, these effects were minimal and are not likely to affect drug targeting or diagnostic imaging on repeat injection.
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UR - http://www.scopus.com/inward/citedby.url?scp=0031807434&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0031807434
VL - 8
SP - 265
EP - 281
JO - Journal of Liposome Research
JF - Journal of Liposome Research
SN - 0898-2104
IS - 2
ER -