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- Dalmo, Johanna, et al.
(författare)
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Priming increases the anti-tumor effect and therapeutic window of 177Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
- 2017
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase 177Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a 177Lu-octreotate priming dose followed 24 h later by a second injection of 177Lu-octreotate compared to a single administration of 177Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice. RESULTS: Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE, BAX, CDKN1A, and GADD45A. CONCLUSIONS: Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for 177Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects.
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- Sandblom, Viktor, 1987, et al.
(författare)
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Radiolabelled pharmaceuticals MIBG and octreotate for treatment of metastatic pheochromocytoma and paraganglioma
- 2014
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Ingår i: SweRays Workshop, Malmö, Sweden, Aug 20-22, 2014.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The 5-year survival for patients with metastatic pheochromocytoma (PC) and paraganglioma (PGL) is less than 50%. There is a clear need for development of better diagnostic and therapeutic options for these patients. Radionuclide therapy offers the possibility to treat spread PC/PGL. The norepinephrine (NE) analogue metaiodobenzylguanidine (MIBG) and the somatostatin (SST) analogues octreotate or octreotide are possible molecules that could be used for this purpose. These analogues have different biodistribution and different organs at risk, when used for therapy. Thus, combined therapy, using both radiolabelled NE and SST analogues, might be beneficial for these patients. Aim: The aim of this study was to evaluate the possibility of using 177Lu-octreotate and/or 131I-MIBG for treatment of patients with metastatic PC/PGL. Materials and Methods: Three patients with metastatic PC/PGL were injected with 131I-MIBG and 111In-octreotide, and four patients with metastatic PC/PGL were injected with 111In-octreotide, before surgical removal of the primary tumour. During surgery, tissue samples of tumour, blood, fat and muscle were collected and weighed, and the radioactivity was measured in a gamma counter. The activity concentration in these tissue samples was then calculated for each radionuclide. Additionally, tumour-to-blood activity concentration ratios (T/B) were calculated. Results: The activity concentrations and T/B values showed large variations between patients. For 111In-octreotide, T/B values were 25-590 and for 131I-MIBG, the corresponding values were 0-1600. Conclusion: The sometimes high T/B values show a clear possibility of using 177Lu-octreotate and 131I-MIBG for treatment of some patients with metastatic PC/PGL. However, due to the large variation between patients, individual investigation of tumour uptake prior to treatment is required.
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