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99mTc-ethylenedicysteine-folate: a new tumor imaging agent. Synthesis, labeling and evaluation in animals
1Department of Nuclear Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs such as methotrexate and overexpressed on various tumor cells. However, these receptors are highly restricted in normal differentiated tissues. Results of limited in vitro and in vivo animal studies suggest that folate receptors could be a potential target for tumor imaging. This study aimed to develop a 99mTc-labeled folic acid using ethylenedicysteine (EC) as a chelator and evaluate its labeling efficiency and potential use as a tumor seeking agent. Tissue distribution of 99mTc-EC-folate was determined in breast tumor-bearing rats at 20 min, 1, 2, and 4 h (n = 3/time interval, 370 KBq/rat, i.v.). Blocking study was employed to determine receptor-mediated process; 99mTc-EC-folate was co-administrated with 50 and 150 mumol/kg of cold folic acid to tumor-bearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 99mTc-EC (control). In animal studies, tumor/blood count density ratios at 20 min-4 h increased from 0.81 +/- 0.09 to 1.23 +/- 0.13 with 99mTc-EC-folate. Conversely, these values showed time-dependent decrease from 0.77 +/- 0.32 to 0.65 +/- 0.01 with 99mTc-EC in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with folic acid co-administrations. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99mTc-EC-folate.
Insights
This study developed a novel 99mTc-labeled folic acid (99mTc-EC-folate) for tumor imaging. The agent successfully visualized tumors in rats, demonstrating its potential as a targeted cancer diagnostic tool.
Area of Science:
- Nuclear medicine
- Radiopharmaceutical chemistry
- Oncology
Background:
- Membrane folic acid receptors are overexpressed on tumor cells but restricted in normal tissues.
- Folate receptors are a potential target for tumor imaging and therapy.
- Developing targeted radiopharmaceuticals is crucial for improved cancer diagnostics.
Purpose of the Study:
- To develop and evaluate a technetium-99m (99mTc)-labeled folic acid using ethylenedicysteine (EC) as a chelator.
- To assess the potential of 99mTc-EC-folate as a tumor-seeking radiopharmaceutical agent.
- To investigate the receptor-mediated uptake mechanism of 99mTc-EC-folate in tumor models.
Main Methods:
- Synthesis of 99mTc-EC-folate using EC as a chelator.
- In vivo tissue distribution studies in breast tumor-bearing rats.
- Blocking studies with cold folic acid to confirm receptor-mediated uptake.
- Planar imaging and whole-body autoradiography.
Main Results:
- 99mTc-EC-folate demonstrated increasing tumor-to-blood count density ratios over time in tumor-bearing rats.
- Control 99mTc-EC showed a time-dependent decrease in tumor-to-blood ratios.
- Co-administration of cold folic acid significantly reduced tumor uptake, confirming receptor-mediated targeting.
- Clear visualization of tumors was achieved with 99mTc-EC-folate in planar images and autoradiograms.
Conclusions:
- 99mTc-EC-folate is a promising radiopharmaceutical for targeted tumor imaging.
- The developed agent exhibits specific uptake in tumors via folate receptors.
- This agent holds potential for non-invasive cancer detection and diagnosis.
