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- Castano, J. P., et al.
(author)
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Gastrointestinal neuroendocrine tumors (NETs) : new diagnostic and therapeutic challenges
- 2014
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In: Cancer Metastasis Review. - : Springer Science and Business Media LLC. - 0167-7659 .- 1573-7233. ; 33:1, s. 353-359
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Research review (peer-reviewed)abstract
- This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.
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| 3. |
- Oyen, W J G, et al.
(author)
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Targeted therapy in nuclear medicine current status and future prospects
- 2007
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:11, s. 1782-1792
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Journal article (peer-reviewed)abstract
- In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.
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| 4. |
- Schmitt, Anneli, 1971, et al.
(author)
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Radiation therapy of small cell lung cancer with 177Lu-DOTA-Tyr3-octreotate in an animal model
- 2004
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In: Journal of nuclear medicine. - 0161-5505. ; 45:9, s. 1542-8
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Journal article (peer-reviewed)abstract
- Small cell lung cancer (SCLC) is a tumor of neuroendocrine (NE) origin with very low survival rate. Somatostatin receptor scintigraphy using 111In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) is a well-established method for the visualization of somatostatin receptor-expressing NE tumors. Recently, new combinations of radionuclides and somatostatin analogs have been investigated for therapeutic purposes. In this study, the somatostatin analog DOTA-Tyr3-octreotate (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid), labeled with the medium-energy electron emitter 177Lu (maximal electron energy = 498 keV, half-life = 6.6 d), was used for radiation therapy of human SCLC in an animal model. METHODS: Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were injected intravenously with 177Lu-DOTA-Tyr3-octreotate. Groups of animals (n = 5 or 6) were injected with 45-, 60-, and 120-MBq fractions and two 45-MBq fractions 48 h apart. Furthermore, 1 control group was treated with unlabeled DOTA-Tyr3-octreotate and another control group was not treated. RESULTS: In both control groups, the tumor volumes were increased 2-fold in approximately 5 d. Treatment with 177Lu-DOTA-Tyr3-octreotate resulted in marked tumor regression with statistically significant tumor volume reduction after 1 wk (P < 0.001). The tumor growth delay time was dependent on the amount of injected activity for the groups with single injections, 26 d for 60 MBq and 40 d for 120 MBq. The best therapeutic effect was obtained in mice injected with 2 fractions of 45 MBq. The relative tumor volume after 1 mo was 0.004 +/- 0.004. CONCLUSION: Radiation therapy with 177Lu-DOTA-Tyr3-octreotate on SCLC-bearing mice was successful. Since the experiments were performed on a human SCLC cell line xenografted to nude mice, the results may be clinically relevant and treatment with 177Lu-DOTA-Tyr3-octreotate could be a treatment alternative in this tumor disease that normally has a dismal prognosis.
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