| 1. |
- Sjöholm, H, et al.
(författare)
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Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat
- 1995
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Ingår i: Anti-Cancer Drugs. - 0959-4973. ; 6:1, s. 109-114
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.
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| 2. |
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| 3. |
- Mårtensson, Linda, et al.
(författare)
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A nonsurgical technique for blood access in extracorporeal affinity adsorption of antibodies in rats.
- 2007
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Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 31:4, s. 312-316
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies for targeting cytotoxic conjugates to tumor cells are currently being evaluated together with extracorporeal affinity adsorption. The aim of the adsorption was to reduce undesired side effects in normal organs and to increase the tumor-to-normal tissue ratios. This technique is also applicable to several other therapeutic areas such as immune-mediated disorders, that is, autoimmunity, allergy, and transplantation rejection. We describe an improved technique for extracorporeal affinity adsorption of radiolabeled biotinylated antibodies in rats. Blood access is established through the tail artery and tail vein, without surgical insertion of permanent catheters. This technique is simple, does not require surgery, and causes only minimal stress to the animals. In addition, experiments can be carried out on several animals simultaneously. This new technique is of considerable benefit for studying extracorporeal affinity adsorption in rats, as experiments can be carried out with negligible anatomical and physiological interventions, compared to previously used techniques.
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| 4. |
- Thörne, Johan, et al.
(författare)
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Effect of ticlopidine and prostaglandin E on endotoxin-induced pulmonary platelet sequestration in vivo
- 1986
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Ingår i: Circulatory Shock. - 0092-6213. ; 20:1, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- Prostaglandin E1 has earlier been shown to decrease pulmonary platelet trapping (PPT) following shock. This experiment was performed to evaluate a new method to study PPT in vivo, and to study the effect of prostaglandin E1 and a new antiplatelet drug (ticlopidine) on PPT in rabbits after i.v. administration of endotoxin. Following platelet labeling with In-111, the rabbits were placed under a scintillation camera for continuous measuring of the activity distribution for 40 minutes. The first five minutes represented reference values, whereafter endotoxin E. coli was injected i.v. The following 2-4 minutes showed a sudden increase of radioactivity over the lungs and a simultaneous decrease over the heart, indicating PPT in the nontreated animals, followed by a slow decrease to almost preshock values during the following 30 minutes. Animals receiving prostaglandin E1 showed a significantly lower activity peak in the lungs after the administration of endotoxin, while the corresponding peak in ticlopidine-treated animals did not differ from that seen in the nontreated animals. In all groups, endotoxin caused a decrease in platelet count, but it was significantly lower in the PGE1-treated animals. The results have shown that this diagnostic model for PPT is reliable and may be used for evaluation of the effect on platelet aggregation in vivo of different drugs
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| 5. |
- Brun, Eva, et al.
(författare)
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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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Ingår i: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Blomqvist, S, et al.
(författare)
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Early post-traumatic changes in hemodynamics and pulmonary ventilation in alcohol-pretreated pigs
- 1987
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Ingår i: Journal of Trauma. - 0022-5282. ; 27:1, s. 40-44
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Tidskriftsartikel (refereegranskat)abstract
- Time relations among trauma, pulmonary and systemic circulation, and lung function were studied in pigs. Eleven animals (b.w. 25-30 kg) were investigated under balanced anesthesia. Ventilation was mechanically controlled. Hemodynamics, pulmonary ventilation, and gas exchange were serially recorded. Seven animals were pretreated with 40% ethanol in saline and four with saline only. Ninety minutes after the ingestion of alcohol or saline, the animals were subjected to a standardized soft-tissue trauma. Cardiac output decreased significantly 2 minutes after trauma and remained low in both groups throughout the observation period of 30 minutes. Pulmonary vascular resistance was significantly increased in the alcohol-pretreated group but was virtually unchanged in the control animals. Systemic vascular resistance was similarly reduced in the two groups. Total compliance was somewhat lower in alcohol-pretreated animals and 10 minutes after the trauma arterial oxygen tension was significantly lower in the alcohol group than in control animals. Carbon dioxide elimination was reduced after trauma in both groups. It is concluded that pulmonary vascular response increased and that total pulmonary compliance is somewhat decreased shortly after trauma in the alcohol group while gas exchange is almost unchanged. The results indicate a negative interaction between alcohol and trauma
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| 7. |
- Altai, Mohamed, et al.
(författare)
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188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
- 2014
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
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| 8. |
- Elgqvist, Jörgen, et al.
(författare)
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Radiosensitivity of Prostate Cancer Cell Lines for Irradiation from Beta Particle-emitting Radionuclide ¹⁷⁷Lu Compared to Alpha Particles and Gamma Rays
- 2016
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Ingår i: Anticancer research. - 1791-7530. ; 36:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The purpose of the present study was to investigate the radiosensitivity of the prostate cancer cell lines LNCaP, DU145, and PC3 when irradiated with beta particles emitted from (177)Lu, and to compare the effect with irradiation using alpha particles or gamma rays.MATERIALS AND METHODS: Cells were irradiated with beta particles emitted from (177)Lu, alpha particles from (241)Am, or gamma rays from (137)Cs. A non-specific polyclonal antibody was labeled with (177)Lu and used to irradiate cells in suspension with beta particles. A previously described in-house developed alpha-particle irradiator based on a (241)Am source was used to irradiate cells with alpha particles. External gamma-ray irradiation was achieved using a standard (137)Cs irradiator. Cells were irradiated to absorbed doses equal to 0, 0.5, 1, 2, 4, 6, 8, or 10 Gy. The absorbed doses were calculated as mean absorbed doses. For evaluation of cell survival, the tetrazolium-based WST-1 assay was used. After irradiation, WST-1 was added to the cell solutions, incubated, and then measured for level of absorbance at 450 nm, indicating the live and viable cells.RESULTS: LNCaP, DU145, and PC3 cell lines all had similar patterns of survival for the different radiation types. No significant difference in surviving fractions were observed between cells treated with beta-particle and gamma-ray irradiation, represented for example by the surviving fraction values (mean±SD) at 2, 6, and 10 Gy (SF2, SF6, and SF10) for DU145 after beta-particle irradiation: 0.700±0.090, 0.186±0.050 and 0.056±0.010, respectively. A strong radiosensitivity to alpha particles was observed, with SF2 values of 0.048±0.008, 0.018±0.006 and 0.015±0.005 for LNCaP, DU145, and PC3, respectively.CONCLUSION: The surviving fractions after irradiation using beta particles or gamma rays did not differ significantly at the absorbed dose levels and dose rates used. Irradiation using alpha particles led to a high level of cell killing. The results show that the beta-particle emitter (177)Lu as well as alpha-particles are both good candidates for radionuclide-therapy applications in the treatment of prostate cancer.
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| 9. |
- Evertsson, Maria, et al.
(författare)
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Combined Magnetomotive ultrasound, PET/CT, and MR imaging of (68)Ga-labelled superparamagnetic iron oxide nanoparticles in rat sentinel lymph nodes in vivo
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Current methods for intra-surgical guidance to localize metastases at cancer surgery are based on radioactive tracers that cause logistical challenges. We propose the use of a novel ultrasound-based method, magnetomotive ultrasound (MMUS) imaging that employ a nanoparticle-based contrast agent that also may be used for pre-operative PET/MRI imaging. Since MMUS is radiation free, this eliminates the dependence between pre- and intra-operative imaging and the radiation exposure for the surgical staff. This study investigates a hypothetical clinical scenario of pre-operative PET imaging, combined with intra-operative MMUS imaging, implemented in a sentinel lymph node (SLN) rat model. At one-hour post injection of (68)Ga-labelled magnetic nanoparticles, six animals were imaged with combined PET/CT. After two or four days, the same animals were imaged with MMUS. In addition, ex-vivo MRI was used to evaluate the amount of nanoparticles in each single SLN. All SLNs were detectable by PET. Four out of six SLNs could be detected with MMUS, and for these MMUS and MRI measurements were in close agreement. The MRI measurements revealed that the two SLNs undetectable with MMUS contained the lowest nanoparticle concentrations. This study shows that MMUS can complement standard pre-operative imaging by providing bedside real-time images with high spatial resolution.
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| 10. |
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