Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo.

Abstract

PURPOSE:

There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.

METHODS:

Biodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of (131)I and (99m)Tc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, (99m)Tc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration.

RESULTS:

NIS-expressing neuroendocrine tumors strongly accumulated (131)I and (99m)Tc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of (131)I or (99m)Tc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of (99m)Tc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of (99m)Tc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons.

CONCLUSIONS:

NIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.

• Authors: Meike L Schipper, Christoph G U Riese, Stephan Seitz, Alexander Weber, Martin Béhé, Tino Schurrat, Nils Schramm, Boris Keil, Heiko Alfke, Thomas M Behr
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 34 Issue 5 Pg. 638-650 (May 2007) ISSN: 1619-7070 [Print] Germany
• PMID: 17160413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iodine Radioisotopes
• Radioisotopes
• Radiopharmaceuticals
• Symporters
• sodium-iodide symporter
• Sodium Pertechnetate Tc 99m

Topics

• Animals
• Cell Line, Tumor
• Humans
• Iodine Radioisotopes (therapeutic use)
• Magnetic Resonance Imaging (methods)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neuroendocrine Tumors (diagnostic imaging, therapy)
• Radioisotopes (therapeutic use)
• Radiopharmaceuticals
• Radiotherapy (methods)
• Sodium Pertechnetate Tc 99m
• Symporters (metabolism)
• Tomography, Emission-Computed, Single-Photon (methods)