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Updated: May 3, 2026
Intraventricular Drug Delivery and Sampling for Pharmacokinetics and Pharmacodynamics Study
Published on: March 31, 2022
Antimicrobial distribution from local delivery depends on dose : a pilot study with MRI
Alex McLaren1, Morgan B Giers, James Fraser
1Banner Good Samaritan Orthopaedic Residency, Banner Good Samaritan Medical Center, 901 E Willetta Road, 2nd Floor, Phoenix, AZ, 85006, USA.
Background:
Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement.
Questions/Purposes:
We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.
Methods:
A 1-cm3 soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 μg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA.
Results:
The volume of tissue with more than 14 μg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p=0.02) (2121 mm3 for 10 g and 665 mm3 for 1 g) and smaller with time for the 10-g formulation (2121 mm3 on Day 7 and 1241 mm3 on Day 14).
Conclusions:
Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time.
Clinical Relevance:
For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.
Insights
Higher gadolinium loads in bone cement led to greater volumes of tissue with high concentrations of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) for longer durations. This indicates that increasing antimicrobial loads may enhance local delivery effectiveness.
Area of Science:
- Biomedical Engineering
- Materials Science
- Radiology
Background:
- Previous studies quantified tissue distribution of gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) over 5 hours in rabbits using 7-T MRI.
- The impact of Gd-DTPA load in bone cement on local tissue distribution duration after surgery remained unknown.
Purpose of the Study:
- To determine if the Gd-DTPA load in bone cement influences local tissue distribution over a 1-month period.
- To assess the relationship between gadolinium concentration in bone cement and its sustained release in local tissues.
Main Methods:
- A rabbit model with a 1-cm3 soft tissue dead space in the quadriceps was used.
- The dead space was filled with bone cement containing varying gadolinium loads.
- Tissue volumes with Gd-DTPA concentrations >14 μg/mL were measured using 7-T MRI at 7, 14, and 33 days.
Main Results:
- Higher gadolinium loads resulted in significantly larger volumes of tissue with high Gd-DTPA concentration on Day 7 (p=0.02).
- For the 10-g gadolinium load, the distribution volume decreased over time (2121 mm3 on Day 7 to 1241 mm3 on Day 14).
Conclusions:
- The volume of distribution and duration of Gd-DTPA in local tissues increased with higher loads in the bone cement.
- Sustained high antimicrobial concentrations in local tissues are achievable with increased antimicrobial loads in delivery systems.
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