Somatostatin Receptors in Malignant Lymphomas: Targets for Radiotherapy?

Journal of Nuclear Medicine

Anton W. Langerak¹  Virgil A.S.H. Dalm¹  Frank T.J. Staal¹  Leo J. Hofland¹  Steven W.J. Lamberts¹  Cornelia M. Mooy¹  Aart-Jan van der Lely¹  Peter M. van Koetsveld¹  Marlijn A. Waaijers¹  Martin P. van Hagen¹ 

关键词: lymphoma;    radiotherapy;    somatostatin receptor;    autoradiography;    internalization;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 sst1−5 mRNA. Receptor autoradiography studies using [125I-Tyr3]octreotide were performed to evaluate binding to sst on cryostat sections of lymphomas. Immunohistochemistry was used to investigate expression of sst2 and sst3. Membrane binding studies and in vitro internalization experiments using [125I-Tyr3]octreotide were performed to study binding and uptake of [125I-Tyr3]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 sst2 and sst3 messenger RNA (mRNA) was demonstrated. By quantitative RT-PCR, expression levels of sst2 and sst3 mRNA were relatively low. Autoradiography studies revealed low binding of [125I-Tyr3]octreotide, whereas immunoreactivity could not be detected for sst2 and sst3 by immunohistochemistry. On the lymphoid cell lines only low numbers of high-affinity SS binding sites were found. In vitro, uptake of [125I-Tyr3]octreotide by these cells was also very low. Conclusion: 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.

【 授权许可】

Unknown