Somatostatin receptors in malignant lymphomas: targets for radiotherapy?
Somatostatin (SS) receptor (sst) scintigraphy is widely used in the visualization of neuroendocrine tumors expressing sst, and radiotherapy using radionuclide-labeled SS analogs has been introduced for treatment of patients with neuroendocrine tumors. Previous sst scintigraphy studies revealed that malignant lymphomas can also be visualized using this technique. The question has been addressed whether lymphomas might also be possible targets for radiotherapy using radionuclide-labeled SS analogs. Therefore, we investigated in vitro the characteristics of lymphoma tissues and lymphoid cell lines to evaluate whether lymphomas can be targets for radiotherapy.


METHODS
Six orbital lymphomas, 2 Hodgkin's lymphomas, and 2 non-Hodgkin's lymphomas from the neck region were collected. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RT-PCR were performed to detect and quantify the expression of sst(1-5) mRNA. Receptor autoradiography studies using [(125)I-Tyr(3)]octreotide were performed to evaluate binding to sst on cryostat sections of lymphomas. Immunohistochemistry was used to investigate expression of sst(2) and sst(3). Membrane binding studies and in vitro internalization experiments using [(125)I-Tyr(3)]octreotide were performed to study binding and uptake of [(125)I-Tyr(3)]octreotide by lymphoid cell lines (JY, TMM, APD) and primary cells derived from a B-cell-derived chronic lymphatic leukemia.


RESULTS
A selective expression of sst(2) and sst(3) messenger RNA (mRNA) was demonstrated. By quantitative RT-PCR, expression levels of sst(2) and sst(3) mRNA were relatively low. Autoradiography studies revealed low binding of [(125)I-Tyr(3)]octreotide, whereas immunoreactivity could not be detected for sst(2) and sst(3) by immunohistochemistry. On the lymphoid cell lines only low numbers of high-affinity SS binding sites were found. In vitro, uptake of [(125)I-Tyr(3)]octreotide by these cells was also very low.


CONCLUSIONS
On the basis of our findings, we conclude that lymphomas do not appear to be candidates for radiotherapy using radionuclide-labeled SS analogs. However, lymphomas are highly radiosensitive tumors and further clinical studies should be performed to evaluate whether the low receptor density is sufficient for targeting treatment in these tumors.
Dalm
Virgil A S H
VA
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. p.m.vanhagen@erasmusmc.nl
Hofland
Leo J
LJ
Mooy
Cornelia M
CM
Waaijers
Marlijn A
MA
van Koetsveld
Peter M
PM
Langerak
Anton W
AW
Staal
Frank T J
FT
van der Lely
Aart-Jan
AJ
Lamberts
Steven W J
SW
van Hagen
Martin P
MP
D000818:Animals; D001345:Autoradiography; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000145:classification / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011878:Radiotherapy / Q000379:methods*; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C114933:octreotide, iodoTyr(3)-; C103631:somatostatin receptor 3; C093733:somatostatin receptor 2; D015282:Octreotide