Browsing by keyword "Radioisotopes"
Now showing items 1-6 of 6
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A comparison of the biological effective dose of 50-kV electronic brachytherapy with (192)Ir high-dose-rate brachytherapy for vaginal cuff irradiationPURPOSE: Advantages for electronic brachytherapy (EBT) of the vaginal cuff include decreased physical dose to the bladder and rectum. Here we compare (192)Ir with EBT using biological effective dose (BED) to account for the different radiobiological effectiveness (RBE) predicted for low-energy x-rays. METHODS AND MATERIALS: Fifteen data sets from five consecutive postoperative endometrial cancer patients treated with EBT were analyzed. Treatment planning was performed using PLATO software. The dose was prescribed as 21Gy in three fractions to a depth of 0.5cm. Physical dose, BED(3), and BED(10) were evaluated for the mucosa, bladder, and rectum. An RBE value of 1.5 was used for BED calculations. RESULTS: Mucosal physical dose is 28.4% greater with EBT (36.6 vs. 28.5Gy, p<0.05). However, the BED(10) is increased by 79.1% (55.6 vs. 99.6Gy, p<0.05) and the BED(3) by 71.5% (118.8 vs. 203.7Gy, p<0.05). The physical dose (dose to 50% volume of the organ) to the bladder (9.3 vs. 6.6Gy, p<0.05) and rectum (7.2 vs. 4.2Gy, p<0.05) are reduced with EBT. BED(3) to the rectum and bladder are also reduced but to a lesser extent (13 vs. 8.3Gy, p<0.05; 18.9 vs. 14.7Gy, p=0.06, respectively). CONCLUSIONS: BED takes into account the higher RBE of low-energy photons generated with EBT and provides a more accurate estimate of the biological effect. When using EBT, physical dose may underestimate the biological effect on the vaginal mucosa and overestimate the benefit for the bladder and rectum. Dose adjustment for EBT based on BED should be considered. rights reserved.
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A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires further validation in tumored mice before clinical trials. We now report on a therapeutic study in mice pretargeted with MORF-CC49 (an anti-TAG-72 antibody CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose-escalating therapeutic study, a pretargeting study in LS174T tumored mice was performed at tracer levels. By both necropsy and imaging, the tracer study showed that the whole body radioactivity was largely restricted to tumor in the mice pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained over 90 h. After decay correction, a best-fit to the biodistribution provided the areas under the radioactivity curves (AUCs) used for the radiation dose estimates. The tumor to normal organ AUC ratios in all cases were greater than unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but temporary tumor remission was evident in 3 out of the 5 animals. Histological examination of tissues from these animals showed no evidence of cytotoxicity to normal tissues but obvious radiation damage to tumor. In conclusion, effective radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re as the therapeutic radionuclide and CC49 as the pretargeting antibody.
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Afterloading: The Technique That Rescued BrachytherapyAlthough brachytherapy had been established as a highly effective modality for the treatment of cancer, its application was threatened by mid-20th century due to appreciation of the radiation hazard to health care workers. This review examines how the introduction of afterloading eliminated exposure and ushered in a brachytherapy renaissance.
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Labeling biomolecules with radiorhenium: a review of the bifunctional chelatorsFor radiotherapy, biomolecules such as intact antibodies, antibody fragments, peptides, DNAs and other oligomers have all been labeled with radiorhenium ((186)Re and (188)Re). Three different approaches have been employed that may be referred to as direct, indirect and integral labeling. Direct labeling applies to proteins and involves the initial reduction of endogenous disulfide bridges to provide chelation sites. Indirect labeling can apply to most biomolecules and involves the initial attachment of an exogenous chelator. Finally, integral labeling is a special case applying only to small molecules in which the metallic radionuclide serves to link two parts of a biomolecule together in forming the labeled complex. While the number of varieties for the direct and integral radiolabeling approaches is rather limited, a fairly large and diverse number of chelators have been reported in the case of indirect labeling. Our objective herein is to provide an overview of the various chelators that have been used in the indirect labeling of biomolecules with radiorhenium, including details on the labeling procedures, the stability of the radiolabel and, where possible, the influence of the label on biological properties.
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Radiolabeling of MAG3-morpholino oligomers with 188Re at high labeling efficiency and specific radioactivity for tumor pretargetingWe are investigating a novel pretargeting approach involving an initial IV injection of antitumor antibody conjugated with a phosphorodiamidate morpholino oligomer (MORF, a DNA analog) and the subsequent IV injection of the radiolabeled complement oligomer (cMORF). In this paper, the cMORF was labeled with (188)Re using MAG(3) as chelator for therapeutic applications. Since (c)MORFs are unstable in acidic condition, an optimal labeling pH was first selected and the other labeling factors were then examined. A labeling efficiency of greater than 90% can be achieved even at a concentration of MAG(3)-cMORF as low as 0.8 microM. The labeled cMORF is stable and capable of hybridizing to its complement.
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Successful radiotherapy of tumor in pretargeted mice by 188Re-radiolabeled phosphorodiamidate morpholino oligomer, a synthetic DNA analoguePURPOSE: Pretargeting has been attracting increasing attention as a drug delivery approach. We recently proposed Watson-Crick pairing of phosphorodiamidate morpholino oligomers (MORF) for the recognition system in tumor pretargeting. MORF pretargeting involves the initial i.v. injection of a MORF-conjugated antitumor antibody and the subsequent i.v. injection of the radiolabeled complement. Our laboratory has reported on MORF pretargeting for diagnosis using (99m)Tc as radiolabel. We now report on the use of MORF pretargeting for radiotherapy in a mouse tumor model using (188)Re as the therapeutic radiolabel. EXPERIMENTAL DESIGN: An initial tracer study was done to estimate radiation dose, and was followed by the radiotherapy study at 400 muCi per mouse with three control groups (untreated, MORF antibody alone, and (188)Re complementary MORF alone). RESULTS: Tracer study indicated rapid tumor localization of (188)Re and rapid clearance from normal tissues with a tumor area under the curve (AUC) about four times that of kidney and blood (the normal organs with highest radioactivity). Tumor growth in the study group ceased 1 day after radioactivity injection, whereas tumors continued to grow at the same rate among the three control groups. At sacrifice on day 5, the average net tumor weight in the study group was significantly lower at 0.68 +/- 0.29 g compared with the three control groups (1.24 +/- 0.31 g, 1.25 +/- 0.39 g, and 1.35 +/- 0.41 g; Ps < 0.05), confirming the therapeutic benefit observed by tumor size measurement. CONCLUSIONS: MORF pretargeting has now been shown to be a promising approach for tumor radiotherapy as well as diagnosis.