| 1. |
- Andersson, J, et al.
(author)
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A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin (R)) on a named patient basis in Sweden
- 2002
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 276-281
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Journal article (peer-reviewed)abstract
- Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p=0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.
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| 2. |
- Kurkus, Jan, et al.
(author)
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Biocompatibility of a novel avidin-agarose adsorbent for extracorporeal removal of redundant radiopharmaceutical from the blood.
- 2007
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In: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 31:3, s. 208-214
-
Journal article (peer-reviewed)abstract
- The use of monoclonal antibodies (MAbs) in cytotoxic conjugates (radionuclides, toxins, or drugs) for targeting tumor cells is restricted due to toxicity in vital organs. Through improved tumor targeting, it is possible to administer larger amounts of such labeled MAbs, thus improving the ability to eradicate tumor cells without increased normal organ toxicity. Extracorporeal affinity adsorption treatment (ECAT) has therefore been developed using an avidin-agarose (AA) adsorbent with high binding affinity for the biotinylated radiolabeled MAb, rituximab. During ECAT, excess radioimmunoconjugates, not bound to the tumor cells, can be removed improving tumor targeting. The present study was performed to estimate the biocompatibility of the AA adsorber. Seven patients with B-cell lymphoma not responding to conventional treatment were studied. During the ECAT procedure, blood (B) components, plasma (P) complement fragments C3a, C5a, and P-bradykinin were analyzed, and other laboratory tests were carried out. Slight decreases in B-hemoglobin (8.3%), B-thrombocytes (11.4%), and P-albumin (14.3%) were observed, and could be explained by the dilution of the blood with normal saline and acid citrate dextrose. The AA adsorbent had no effect on the blood cells, immunological status or P-bradykinin level. The AA adsorber demonstrated good hemocompatibility and biocompatibility, without any side effects in the patients.
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| 3. |
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| 4. |
- Stockeld, Dag, et al.
(author)
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A Swedish study of chemoradiation in squamous cell carcinoma of the esophagus
- 2001
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40, s. 566-
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Journal article (peer-reviewed)abstract
- This multicenter study describes the development of a chemoradiation protocol for the treatment of non-metastatic squamous cell carcinoma of the esophagus. Eighty patients were treated with three courses of chemotherapy (cisplatinum and 5-fluorouracil) with concomitant radiotherapy (40 Gy) during the last two courses of chemotherapy. Esophagectomy was performed, when feasible. If no operation was performed, patients were planned to receive a target dose of 64 Gy. Toxicity was mainly attributable to hematological impairment and led to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to administer the planned treatment in a gradually higher proportion of patients (13/23 [57%] before changes of treatment compared with 30/36 [83%] after changes). Treatment-related mortality was 3.75% (3 patients, associated with leucopenic septicemia after chemotherapy). Fifty-four patients were resected. No per- or postoperative mortality was encountered. The complete response (pathological CR) rate in operated patients was 46% (27/59 patients) after chemoradiation. In the whole series the CR rate (including clinical CR for non-resected patients) was 44%. With a minimum follow-up of 37 months, the 3-year survival for the whole group was 31% compared with 57% for the CR patients. Total 5-year survival thus far (July 1999) is 26%.
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| 5. |
- Åkervall, Jan, et al.
(author)
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Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients
- 2004
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In: Clinical Cancer Research. - 1078-0432. ; 10:24, s. 8204-8213
-
Journal article (peer-reviewed)abstract
- Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified similar to60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.
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| 6. |
- Berg, Gertrud, 1944, et al.
(author)
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Consequences of inadvertent radioiodine treatment of Graves' disease and thyroid cancer in undiagnosed pregnancy. Can we rely on routine pregnancy testing?
- 2008
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:1, s. 145-9
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Radioiodine and most cytostatic treatments are contraindicated in pregnancy. Still, inadvertent therapy does occur. Radioiodine was given to two pregnant women with Graves' disease and thyroid cancer respectively, both in their 20th gestational week. Routine pregnancy tests based on urinary beta-hCG had failed to indicate pregnancy in both cases. METHODS: Estimation of doses to the foetuses and foetal thyroids. Scrutiny of pregnancy testing. RESULTS AND CONCLUSIONS: Doses to foetal thyroids were ablative (250-600 Gy). Total foetal dose in the Graves' patient was 100 mGy and compatible with survival, whereas a foetal dose of approximately 700 mGy together with induced hypothyroidism was fatal for the foetus of the cancer patient. Routine pregnancy tests may fail early and late in pregnancy. The possibility of pregnancy should be considered in all fertile women before therapy with radionuclides or cytostatic regimens, and a clinical investigation undertaken on wide indications with determination of serum beta-hCG, preferably together with an ultrasound examination.
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| 7. |
- Boulton, A J M, et al.
(author)
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The global burden of diabetic foot disease
- 2005
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In: The Lancet. - 1474-547X. ; 366:9498, s. 1719-1724
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Research review (peer-reviewed)abstract
- Diabetic foot problems are common throughout the world, resulting in major economic consequences for the patients, their families, and society. Foot ulcers are more likely to be of neuropathic origin, and therefore eminently preventable, in developing countries, which will experience the greatest rise in the prevalence of type 2 diabetes in the next 20 years. People at greatest risk of ulceration can easily be identified by careful clinical examination of the feet: education and frequent follow-up is indicated for these patients. When assessing the economic effects of diabetic foot disease, it is important to remember that rates of recurrence of foot ulcers are very high, being greater than 50% after 3 years. Costing should therefore include not only the immediate ulcer episode, but also social services, home care, and subsequent ulcer episodes. A broader view of total resource use should include some estimate of quality of life and the final outcome. An integrated care approach with regular screening and education of patients at risk requires low expenditure and has the potential to reduce the cost of health care.
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| 8. |
- Brans, B, et al.
(author)
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Clinical applications of newer radionuclide therapies
- 2006
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 42:8, s. 994-1003
-
Journal article (peer-reviewed)abstract
- When radio-iodine was first used in the treatment of metastasized thyroid carcinoma in 1943, its success in terms of tumour response, quality of life improvement and survival was considered a 'miracle', as in those days metastatic cancer was generally fatal. Inspired by this, many efforts have been made to apply radioisotope therapy to other tumours. Radionuclide therapy uses radioactive isotopes labelled with specific targeting agents that aim to deliver the irradiation of the isotope to the tumour, while sparing normal tissues. Its unique modality allows to systemically target radiosensitive tumours throughout the body. Another important principle is its so-called 'cross-fire' action, whereby, owing to the larger reach of the radiation in relation to the cell diameter, a tumour cell receives lethal hits also from isotopes in the neighbourhood that are not directly associated with this cell. The treatment is therefore less hampered by inhomogeneous distribution and metabolism than for example chemo- or immunotherapy. The European Association of Nuclear Medicine has issued guidelines on so-called 'established' therapies (www.eanm.org), i.e. hyperthyroidism, thyroid carcinoma, refractory synovitis, bone metastases, mIBG therapy, (32)p therapy and Lipiodol therapy. Newer therapies include radio-peptide therapy, radio-immunotherapy of lymphoma and microsphere therapy for liver cancer. The aim of a recently held workshop at the ECCO13 conference 2005 and this review is to inform the oncology community about these new developing therapies. (c) 2006 Elsevier Ltd. All rights reserved.
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| 9. |
- Brans, B., et al.
(author)
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Clinical radionuclide therapy dosimetry: the quest for the "Holy Gray"
- 2007
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 34:5, s. 772-786
-
Research review (peer-reviewed)abstract
- Introduction Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. Review This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. Developments In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.
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| 10. |
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| 11. |
- Brun, Eva, et al.
(author)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
-
Journal article (peer-reviewed)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 12. |
- Brun, Eva, et al.
(author)
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FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
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In: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 13. |
- Brun, Eva, et al.
(author)
-
Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas
- 2001
-
In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40:4, s. 491-496
-
Journal article (peer-reviewed)abstract
- The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.
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| 14. |
- Carlsson, J, et al.
(author)
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Tumour therapy with radionuclides: assessment of progress and problems
- 2003
-
In: Radiotherapy and Oncology. - 1879-0887. ; 66:2, s. 107-111
-
Research review (peer-reviewed)abstract
- Radionuclide therapy is a promising modality for treatment of tumours of haematopoietic origin while the success for treatment of solid tumours so far has been limited. The authors consider radionuclide therapy mainly as a method to eradicate disseminated tumour cells and small metastases while bulky tumours and large metastases have to be treated surgically or by external radiation therapy. The promising therapeutic results for haematological tumours give hope that radionuclide therapy will have a breakthrough also for treatment of disseminated cells from solid tumours. New knowledge related to this is continuously emerging since new molecular target structures are being characterised and the knowledge on pharmacokinetics and cellular processing of different types of targeting agents increases. There is also improved understanding of the factors of importance for the choice of appropriate radionuclides with respect to their decay properties and the therapeutic applications. Furthermore, new methods to modify the uptake of radionuclides in tumour cells and normal tissues are emerging. However, we still need improvements regarding dosimetry and treatment planning as well as an increased knowledge about the tolerance doses for normal tissues and the radiobiological effects on tumour cells. This is especially important in targeted radionuclide therapy where the dose rates often are lower than 1 Gy/h. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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| 15. |
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| 16. |
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| 17. |
- Dictor, Michael, et al.
(author)
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Determination of nonendemic nasopharyngeal carcinoma by in situ hybridization for Epstein-Barr virus EBER1 RNA: sensitivity and specificity in cervical node metastases.
- 1995
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In: Laryngoscope. - 1531-4995. ; 105:4, s. 407-412
-
Journal article (peer-reviewed)abstract
- After time-consuming and costly investigations, patients with neck metastases from an occult primary often receive unnecessarily large radiation volumes to treat a possible origin in the nasopharynx. In this study a colorimetric antisense Epstein-Barr early ribonucleoprotein 1 (EBER1) oligonucleotide probe specific for Epstein-Barr virus RNA was hybridized in situ to metastatic tissue obtained from 18 nasopharyngeal, 54 oral and pharyngeal, and 12 occult carcinomas derived from an unselected population. All 16 nonkeratinizing nasopharyngeal carcinomas (NPCs) were positive for EBER1. Both cases of keratinizing NPC and all 54 other metastases were negative. A single positive case of occult carcinoma indicated its origin from NPC. In retrospect, 7 patients with occult carcinoma had received unnecessary treatment with irradiation to the nasopharynx. Nasopharyngeal carcinoma appears to be a less common origin of occult carcinoma than previously considered. In the proper clinicopathologic co
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| 18. |
- Elgström, Erika, et al.
(author)
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Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.
- 2014
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In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:4, s. 143-152
-
Journal article (peer-reviewed)abstract
- Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Conclusion: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms.
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| 19. |
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| 20. |
- Elgström, Erika, et al.
(author)
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Pattern of antigen expression in metastases after radioimmunotherapy of a syngeneic rat colon carcinoma utilizing the BR96 antibody.
- 2012
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In: Experimental hematology & oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 1:1
-
Journal article (peer-reviewed)abstract
- Abstract ABSTRACT: BACKGROUND: Repeated administration of antibody-based therapies such as radioimmunotherapy depends on preserved antigen expression in tumor lesions. The purpose of this study was to evaluate whether the antigen expression in metastases observed after radioimmunotherapy differs from that of untreated primary tumors. FINDINGS: 30 of the 35 Brown Norway rats with syngeneic colon carcinoma treated with 400 MBq/kg 177Lu-DOTA-BR96 exhibited consistent complete response of the primary tumor. 13 animals developed metastases that were detected after treatment. The antigen expression was reduced in 17 of 23 metastases detected after radioimmunotherapy compared with untreated tumors. No tumors completely lacked positively stained tumor cells. CONCLUSIONS: Although it was not possible to demonstrate that the antigen reduction is triggered by the radioimmunotherapy this result stress the importance of considering the risk of reduced antigen expression in metastases after radioimmunotherapy prior to further targeted therapies.
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| 21. |
- Elgström, Erika, et al.
(author)
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Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent rat colon carcinoma model.
- 2015
-
In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 5
-
Journal article (peer-reviewed)abstract
- CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established tumors and, above all, if they delay or prevent the development of distant metastases after RIT, using an immunocompetent syngeneic rat colon carcinoma model.
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| 22. |
- Eriksson, Sophie, et al.
(author)
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Repeated Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2012
-
In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:2, s. 134-140
-
Journal article (peer-reviewed)abstract
- Abstract Aim: Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration. Methods: Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the maximal tolerated dose. Results: The additional treatment resulted in tolerable myelotoxicity; however, the frequency of metastatic disease and survival were not affected. Immunohistochemistry demonstrated binding of the BR96 antibody to tissue sections of analyzed metastases. Conclusions: In our model, development of metastatic disease after treatment of the manifest tumor was not prevented by an additional treatment with the same radioimmunoconjugate. Therefore, the antibody should be labeled with a more suitable radionuclide for treatment of metastases. The repeated targeted therapy was well tolerated in aspects of myelotoxicity.
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| 23. |
- Eriksson, Sophie, et al.
(author)
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Sequential Radioimmunotherapy with (177)Lu- and (211)At-Labeled Monoclonal Antibody BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2014
-
In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:6, s. 238-246
-
Journal article (peer-reviewed)abstract
- Abstract Alpha-particle emitters, such as astatine-211 ((211)At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 ((177)Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10MBq/kg body weight of (211)At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any (211)At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Results: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with (211)At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of (177)Lu-BR96 and (211)At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.
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| 24. |
- Eriksson, Sophie, et al.
(author)
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Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb.
- 2013
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In: EJNMMI research. - 2191-219X. ; 3:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with alpha-emitting radionuclides such as astatine-211 (211At). Radioimmunotherapy utilizing alpha-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a 211At-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm. METHODS: Eighteen rats with subperitoneal syngeneic colon carcinoma were allocated to three groups of six animals together with three healthy rats in each group. The groups were injected intravenously with either 150 mug of unlabeled mAbs (controls) or 2.5 or 5 MBq 211At-mAbs directed towards the Lewis Y antigen expressed on the cell membrane of several carcinomas. Tumor volume, body weight, and blood cell counts were monitored for 100 days after treatment. RESULTS: Local tumors were non-palpable in five out of six rats after treatment with both activities of 211At-mAbs, compared to one out of six in the control group. At the study end, half of the animals in each group given 211At-BR96 and one animal in the control group were free from disease. Radioimmunotherapy resulted in dose-dependent, transient weight loss and myelotoxicity. Survival was significantly better in the groups receiving targeted alpha therapy than in those receiving unlabeled mAbs. CONCLUSIONS: This study demonstrates the possibility of treating small, solid colon carcinoma tumors with alpha-emitting radionuclides such as 211At bound to mAbs, with tolerable toxicity.
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| 25. |
- Eriksson, Sophie, et al.
(author)
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Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2012
-
In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:3, s. 175-182
-
Journal article (peer-reviewed)abstract
- Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy.
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