| 1. |
- Garkavij, Michael, et al.
(författare)
-
Lu-177-[DOTA0,Tyr3] Octreotate Therapy in Patients With Disseminated Neuroendocrine Tumors: Analysis of Dosimetry With Impact on Future Therapeutic Strategy
- 2010
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1084-1092
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lu-177-(DOTAO,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan. METHODS: Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex. RESULTS: For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution. CONCLUSIONS: The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. Cancer 2010;116(4 suppl):1084-92. (C) 2010 American Cancer Society.
|
|
| 2. |
- Hindorf, Cecilia, et al.
(författare)
-
Time dependence of the activity concentration ratio of red marrow to blood and implications for red marrow dosimetry.
- 2002
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:4 Suppl, s. 1235-1239
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The method for red marrow dosimetry in radioimmunotherapy, in the absence of specific activity uptake in red marrow, is based on the activity measured in the blood or plasma. The activity concentration ratio of red marrow to blood is then assumed to be constant. The aim of the current study was to determine whether this ratio varies with time after injection. METHODS: Measurements were carried out with both animals and patients.Tumor-bearing rats were intravenously injected with iodine-131-, iodine-125-, indium-111-, or rhenium-188-labeled BR96, a chimeric immunoglobulin G1 monoclonal antibody. (All were chelate-labeled, except for iodine-131, which was iodogen-labeled.) Measurements were made of the activity concentration in blood and bone marrow at different points in time after injection, and the ratio of activity concentration in red marrow and blood as a function of time postinjection (RMBLR[t)]) was calculated. For patients treated with iodine-131-labeled monoclonal antibody (LL2, Immunomedics Inc., Morris Plains, NJ; anti-CD22; immunoglobulin G2 isotype of mouse origin), blood samples were drawn and scintillation camera images taken at different times after injection. The red marrow activity concentration in the sacrum was determined by activity quantification from regions of interest. The activity concentration in blood was also measured. The RMBLR(t) was calculated based on these data. RESULTS: For both patients and rats, the RMBLR(t) was increased 72 hours after injection. Furthermore, it was found that the use of a constant RMBLR can lead to an over- or underestimation of the absorbed dose in bone marrow. CONCLUSIONS: These data demonstrate the difficulty in using fixed values of the activity concentration ratio of red marrow to blood for dosimetry.
|
|
| 3. |
- Lindén, Ola, et al.
(författare)
-
Single tumor cell uptake and dosimetry of technetium-99m Fab ' anti-CD22 in low-grade B-cell lymphoma
- 2002
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:4, s. 1270-1274
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. A patient with follicular lymphoma was investigated with 0.5 mg Fab' anti-CD22 labeled with 1100 MBq technetium-99m (Tc-99m). A computed tomography scan performed a week later revealed regression. This unexpected response prompted an investigation of single cell dosimetry of low-energy electron emitters. METHODS. Another patient with low-grade, unclassifiable B-cell lymphoma with a low expression of CD22 was injected with Tc-99m anti-CD22. Blood samples were drawn 30 minutes, 4 hours, and 24 hours after injection. Lymphoma cells (CD19+) and T cells (CD3+), which served as control cells, were separated using a flow cytometer. The radioactivity of the two cell Populations was Measured in an NaI(Tl) well-type detector. The mean uptake per cell and absorbed dose were calculated. The CD22 expression of the patient's cells and of a B-cell lymphoma cell line (Raji) were assessed by flow cytometry for die extrapolation of the absorbed dose from the patient's cells to a cell line with higher CD22 expression. RESULTS. The average number of Tc-99m atoms per CD19+ and CD3 cell 4 hours postinjection were 5.4 and 0.054, respectively. Depending on the assumed ratio between antibody and CD22 molecules (1:2 or 1:1), the CD22 expression on the patient's cells and Raji cells varied from 2800 to 5700 and from 37,000 to 74,000 per cell, respectively. The average absorbed dose per cell ranged from 4 x 10(-7) to 0.1 grays (Gy). CONCLUSIONS. It seems feasible to assess the mean single tumor cell uptake of Tc-99m targeted by Fab' anti-CD22 in a patient's lymphoma using sorted cell populations, thereby allowing single cell dosimetry. Extrapolation of the absorbed dose from Tc-99m to cells with higher CD22 expression was made and under certain conditions absorbed doses of 0.1 Gy were obtained, indicating the potential relevance of low-energy elCancer 2002;94:1270-4.
|
|
| 4. |
- Mårtensson, Linda, et al.
(författare)
-
High-Dose Radioimmunotherapy Combined With Extracorporeal Depletion in a Syngeneic Rat Tumor Model
- 2010
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1043-1052
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the current study was to investigate the possibility of increasing the maximal tolerated dose (MTD) of a tumor-selective radiolabeled antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated whether this increase in dose improved the therapeutic effect on solid manifest tumors in an immunocompetent animal model. METHODS: Rats were injected with high activities/body weight of lutetium (Lu-177)- or yttrium (Y-90)-labeled antibody conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment 24 hours postinjection. Myelotoxicity was assessed by analysis of blood parameters for 12 weeks. The effect of increased doses in combination with extracorporeal affinity adsorption treatment was evaluated with respect to myelotoxicity and therapeutic effect in a syngeneic rat colon cancer model. RESULTS: The MTD of Lu-177- or Y-90-labeled immunoconjugates could be increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with Lu-177- or Y-90-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 x 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection. CONCLUSIONS: Extracorporeal affinity adsorption treatment is a method that safely and efficiently reduces myelotoxicity associated with RIT. Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. However, because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity in combination with extracorporeal affinity adsorption treatment in this study. Targeted RIT with beta-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease. (C) 2010 American Cancer Society.
|
|
| 5. |
- Wang, Zhongmin, et al.
(författare)
-
Application of extracorporeal immunoadsorption to reduce circulating blood radioactivity after intraperitoneal administration of indium-111-HMFG1-biotin.
- 2002
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:4 Suppl, s. 1287-1292
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Extracorporeal immunoadsorption (ECAT) is a method of reducing activity in radiosensitive organs by removing excess monoclonal antibodies (MAbs) from the blood. Previously, the authors experimentally evaluated ECAT based on the avidin-biotin concept after intravenous administration of radioimmunoconjugates. The aim of the current study was to determine whether ECAT could be used to reduce activity after intraperitoneal (i.p.) administration of indium-111((111)In)-HMFG1-biotin in rats, and to compare the pharmacokinetics of (111)In-HMFG1 with or without attached biotin after i.p. injection. METHODS: HMFG1, a murine immunoglobulin G(1) MAb that recognizes an epitope on the polymorphic epithelial mucin (PEM) antigen, was labeled with (111)In and then biotinylated. ECAT was explored from unseparated blood using an avidin-agarose adsorption column. Thirty rats were used as controls and 13 underwent ECAT. The whole-body (WB), blood, and organ activity were monitored. RESULTS: The binding capacity of (111)In-HMFG1-biotin to avidin was high. Biotinylation did not enhance the excretion of HMFG1. When ECAT was employed, the WB and blood radioactivity were reduced by 35-40% (P < 0.05) and 75--86% (P < 0.01), respectively. After the completion of ECAT, the activity uptake in organs was significantly decreased. CONCLUSIONS: ECAT was successfully applied after i.p. injection of the (111)In-HMFG-biotin MAb to reduce the radioactivity in the WB, blood, and radiosensitive organs. Due to redistribution of the radiolabeled MAbs during and after the completion of ECAT, the adsorption may have been prolonged or repeated. Biotinylation did not significantly change the biodistribution of the (111)In-HMFG1 in rats after intraperitoneal injection.
|
|
| 6. |
- Strand, Sven-Erik, et al.
(författare)
-
Small animal imaging with pinhole single-photon emission computed tomography
- 1994
-
Ingår i: Cancer. - 1097-0142. ; 73:Suppl. 3, s. 981-984
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. High resolution spatial details of the distribution of activity in three dimensions is required to evaluate the localization and dosimetric properties of radiolabelled monoclonal antibodies in tumors and normal tissues. Planar imaging of small animals with a resolution of 5-10 mm is usually the imaging modality of choice. The authors investigated high resolution single-photon emission computed tomographic (SPECT) imaging, based on a rotating pinhole scintillation camera. Although the sensitivity of the pinhole collimator is low, several radionuclides offer suitable decay properties to perform pinhole SPECT, especially in conjunction with high activity levels used in radioimmunotherapy. METHODS. Transverse, sagittal, and coronal sections were reconstructed using a three-dimensional cone-beam algorithm, which is a generalization of the two-dimensional fan-beam filtered backprojection algorithm. Before reconstruction, the pinhole projections were corrected for the decay of the radionuclide, geometric and intrinsic efficiency variations of the camera system, and center of rotation shift. RESULTS. The spatial resolution at 50 mm from the pinhole collimator with 3.3 mm aperture was 3.4 mm, and the sensitivity 7.2 c/s microCi for technetium-99m. With the 2 mm collimator the resolution was 2.2 mm, and the sensitivity was 2.6 c/s/microCi. To show the spatial resolution in vivo, a rat was injected with 185 MBq of technetium-99m-methylene diphosphonate or with 5 mCi technetium-99m-hexamethylpropylene amine oxime. The bone structures were well delineated in the methylene diphosphonate image, and in the hexamethylpropylene amine oxime image, the brain was nicely shown. For comparison a magnetic resonance image for the same section was done. CONCLUSIONS. High resolution SPECT imaging with the pinhole collimator provides mapping of the activity in three-dimensions, needed for more detailed biodistribution data and to perform more accurate dosimetry.
|
|
| 7. |
- Strand, Sven-Erik, et al.
(författare)
-
A general extracorporeal immunoadsorption method to increase tumor-to-tissue ratio
- 1994
-
Ingår i: Cancer. - 1097-0142. ; 73:3 Suppl, s. 1033-1037
-
Tidskriftsartikel (refereegranskat)abstract
- The idea of applying extracorporeal immunoadsorption (ECIA) in radioimmunodiagnosis and radioimmunotherapy has been proposed previously. The authors here report on the development of new concept using a general method for ECIA based on biotinylated MoAb adsorbed on an avidin column. Athymic rats heterotransplanted with either human melanomas or human lung carcinoma were injected with iodine-125-labeled biotinylated 96.5 or L6 MoAb, respectively. At 24 or 48 hours after the injection, ECIA was performed by pumping blood through a hollow-fiber plasma filter. The separated plasma then was passed through an absorbent (avidin-agarose) column. The whole ECIA procedure lasted for 3 hours. By this ECIA method, the tumor-to-normal tissue ratios were increased in various tissues (i.e., radiosensitive and blood rich organs) by a factor of four to five.
|
|
