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Enhanced drug retention in VX2 tumors by use of degradable starch microspheres
Abstract:
Twenty-nine rabbits with 12- to 14-day-old VX2 tumors in the hind leg were injected intraarterially with technetium-99m (99mTc) DTPA and various combinations of biodegradable starch microspheres, Spherex (Pharmacia, Sweden), to evaluate the efficacy of the microspheres in enhancing tumor retention of 99mTc DTPA. A gamma camera and nuclear medicine computer were used to generate time activity curves of 99mTc DTPA concentration in the tumors. Blood flow to the tumor and various muscles was also measured at intervals by left ventricular injection of 15 micron radiolabeled plastic microspheres. Ninety minutes following the administration of 99mTc DTPA, specimens from the tumor, plasma and different muscles were counted in a NaI well counter connected to a multichannel analyzer. When biodegradable microspheres mixed with 99mTc DTPA were injected and followed by a slow infusion of plain starch microspheres, the 99mTc DTPA was retained in the tumor at concentrations up to 11 times that seen when 99mTc DTPA alone was injected; the corresponding biological half-time was 13 times longer than control values. Additionally, the degree of drug retention was inversely related to blood flow, with retention increasing as blood flow decreased. The results have possible applications to the use of biodegradable microspheres in the intraarterial delivery of chemotherapeutic agents to solid tumors.
Insights
Biodegradable microspheres significantly enhance tumor retention of technetium-99m DTPA in rabbits. This method increases drug concentration and prolongs retention time, showing promise for cancer therapy.
Area of Science:
- Nuclear Medicine
- Biomedical Engineering
- Oncology
Background:
- Effective intra-arterial delivery of chemotherapeutic agents to solid tumors remains a challenge.
- Enhancing drug retention within tumors can improve therapeutic efficacy and reduce systemic toxicity.
- Biodegradable microspheres offer potential for localized drug delivery and sustained release.
Purpose of the Study:
- To evaluate the efficacy of biodegradable starch microspheres in enhancing tumor retention of technetium-99m DTPA (99mTc DTPA).
- To investigate the relationship between microsphere administration, drug retention, and tumor blood flow.
Main Methods:
- VX2 tumors were established in rabbit hind legs.
- Intra-arterial injection of 99mTc DTPA with or without biodegradable starch microspheres (Spherex).
- Gamma camera imaging and nuclear medicine computer analysis to generate time-activity curves.
- Measurement of tumor and muscle blood flow using radiolabeled plastic microspheres.
- Quantification of 99mTc DTPA concentration in tumor, plasma, and muscle tissues.
Main Results:
- Mixing biodegradable microspheres with 99mTc DTPA and infusing plain microspheres increased tumor retention up to 11-fold compared to 99mTc DTPA alone.
- The biological half-time of 99mTc DTPA in tumors was extended by 13 times.
- Drug retention was inversely correlated with tumor blood flow; lower blood flow resulted in higher retention.
Conclusions:
- Biodegradable starch microspheres effectively enhance the intra-arterial tumor retention of 99mTc DTPA.
- This approach offers a promising strategy for improving localized chemotherapy delivery to solid tumors.
- The inverse relationship between retention and blood flow highlights the potential for targeted delivery in specific tumor microenvironments.