Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo.
OBJECTIVE
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.
Schipper
Meike L
ML
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany. mshipper@stanford.edu.|Molecular Imaging Program at Stanford (MIPS) and Department of Radiology, Stanford University, E 150 Clark Center, 318 Campus Drive, Stanford, CA, 94305-5427, USA. mshipper@stanford.edu.
Riese
Christoph G U
CGU
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany.
Seitz
Stephan
S
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany.
Weber
Alexander
A
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany.
Béhé
Martin
M
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany.
Schurrat
Tino
T
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany.
Schramm
Nils
N
Department of Electronics, Forschungszentrum Jülich, Jülich, Germany.
Keil
Boris
B
Department of Radiology, Philipps University Marburg, Marburg, Germany.
Alfke
Heiko
H
Department of Radiology, Philipps University Marburg, Marburg, Germany.
Behr
Thomas M
TM
Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany.
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000628:therapy*; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals; D011878:Radiotherapy / Q000379:methods*; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters