| 1. |
- Andersson, Charlotte, et al.
(författare)
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Recombinant alpha(1)-Microglobulin Is a Potential Kidney Protector in Lu-177-Octreotate Treatment of Neuroendocrine Tumors
- 2019
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 60:11, s. 1600-1604
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of neuroendocrine tumors with Lu-177-octreotate results in prolonged survival and improved quality of life for the patient. However, the treatment is today limited by side effects on kidney and bone marrow, and complete tumor remission is rarely seen. A possible way to minimize dose-limiting toxicity and to optimize this treatment method is to use radioprotectors in conjunction with radiotherapy. A recombinant form of alpha(1)-microglobulin ( rA1M) was recently shown to preserve kidney structure and function after Lu-177-octreotate injection in mice and was suggested as a radioprotector in peptide receptor radionuclide therapy. The aims of this work were to investigate the influence of rA1M on the in vivo biokinetics of Lu-177-octreotate, with a focus on tumor tissue, and to study the impact of rA1M on the therapeutic response in tumor tissue subjected to Lu-177-octreotate treatment. Methods: The biodistribution of Lu-177-octreotate was examined in BALB/c nude mice with GOT2 tumors 1-168 h after injection with either Lu-177-octreotate or coadministration of 177Lu-octreotate and rA1M. The effects of rA1M on the tumor response after Lu-177-octreotate treatment were studied in BALB/c nude mice with GOT1 tumors. Three groups of mice were administered rA1M, Lu-177-octreotate, or both. Another group served as untreated controls. Tumor volume was measured to follow the treatment effects. Results: No statistically significant difference in biodistribution of Lu-177 was observed between the groups receiving Lu-177-octreotate or coinjection of Lu-177-octreotate and rA1M. The therapy study showed a decrease in mean tumor volume during the first 2 wk for both the Lu-177-octreotate group and the coadministration group, followed by tumor regrowth. No statistically significant difference between the groups was found. Conclusion: rA1M did not negatively impact absorbed dose to tumor or therapeutic response in combination with Lu-177-octreotate and may be a promising kidney protector during Lu-177-octreotate treatment of patients with neuroendocrine tumors.
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| 2. |
- Arne, Gabriella, et al.
(författare)
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Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
- 2013
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 52:4, s. 783-792
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Tidskriftsartikel (refereegranskat)abstract
- Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05). Conclusion. Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.
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| 3. |
- Carlsson, J, et al.
(författare)
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Therapy with radiopharmaceuticals
- 2002
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Ingår i: Acta Oncologica. - 1651-226X. ; 41:7-8, s. 623-628
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Tidskriftsartikel (refereegranskat)abstract
- In an investigation by the Swedish Cancer Society, an expert group described the present status, critical issues and future aspects and potentials for each of nine major areas of radiation therapy research. The present report deals with therapy with radiopharmaceuticals.
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| 4. |
- Jakobsen, A M, et al.
(författare)
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Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.
- 2001
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Ingår i: The Journal of pathology. - : Wiley. - 0022-3417. ; 195:4, s. 463-72
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.
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| 5. |
- Kristiansson, A., et al.
(författare)
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Correction to: Protection of Kidney Function with Human Antioxidation Protein α1-Microglobulin in a Mouse 177Lu-DOTATATE Radiation Therapy Model by Kristiansson A, Ahlstedt J, Holmqvist B, Brinte A, Tran TA, Forssell-Aronsson E, Strand S-E, Gram M, and Åkerström B. Antioxidants & Redox Signaling 30: 1746-1759, 2019. DOI: 10.1089/ars.2018.7517.
- 2020
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Ingår i: Antioxidants & redox signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 32:9
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
- Romiani, Arman, 1991, et al.
(författare)
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Neuroblastoma xenograft models demonstrate the therapeutic potential of Lu-177-octreotate
- 2021
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40-50%, indicating the need for novel and improved treatment options. Lu-177-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of Lu-177-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of Lu-177-octreotate for treatment of NB. Methods BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts (n = 5-7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq Lu-177-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1-5, and Ki67 were carried out for tumor xenografts from the three cell lines. Results High Lu-177 concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq Lu-177-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq Lu-177-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32. Conclusion T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of Lu-177-octreotate as a therapeutic alternative for metastatic NB.
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| 8. |
- Schüler, Emil, et al.
(författare)
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Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.
- 2015
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys). At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a) global transcriptional variations in kidney tissues, (b) morphological changes in the kidneys, (c) changes in white and red blood cell count as well as blood levels of urea, and (d) changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.
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