1662 Objectives: Repeated trials of radioimmunotherapy (RIT) with high-dose anti-CD20 I-131 rituximab could be an approach that is useful to raise therapy efficacy in the treatment of non-Hodgkin’s lymphoma (NHL). In this study, we evaluate the absorbed dose of whole-body and red marrow in repeated RIT studies with administration of high-dose I-131 rituximab, using high-dose gamma imaging. Methods: Total 15 RIT studies with therapeutic dose of I-131 rituximab (7536 ± 1211 MBq) were performed on 6 patients with NHL. The number of repeated administration was 2 for 5 patients and 5 for one patient. The interval between repeated administrations was 13.9 ± 6.8 weeks. Whole-body planar images were acquired sequentially for 5 days using a gamma camera (Scintron, MiE, Germany) with high-energy collimator. Serial venous blood samples were obtained at the same points of imaging time. During the emission scan, several standard sources were placed beside patient in the field of view. All anterior and posterior images were converted to geometric-mean images with corrections of dead-time, physical-decay and attenuation, and used in further analysis for dosimetry. The time-activity curves (TACs) of whole-body and blood were used to estimate residence time and absorbed dose of whole-body and red marrow, respectively. Results: The shape of TACs was not different between repeated studies. The residence time of whole-body and blood were 25.7 ± 5.0 hr and 0.8 ± 0.4 hr, respectively. The values of absorbed dose were 29.8 ± 8.2 cGy for whole-body and 44.0 ± 19.6 cGy for red marrow, respectively, and showed the linear relationship with the amount of administered I-131 rituximab (r2 = 0.5971 for whole-body, r2 = 0.7423 for red marrow). Conclusions: The bio-kinetics of I-131 rituximab in repeated RIT was similar between studies. This dosimetry strategy in repeated RIT study with high-dose I-131 rituximab would be useful in monitoring and planning of treatment for NHL, with improved efficacy and safety.
Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas.Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS).Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively.131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.
1010 Objectives We describe the synthesis and in vivo application of gold nanoparticles coated with Gd-chelate (Au@GdL), for use as a potential bimodal MR/CT contrast agent and investigate the cell labeling efficiencies of Au@GdL. Methods The ligand (L), a conjugate of DTPA with cysteine, was prepared from the reaction of DTPA-bis(anhydride) with two equivalents of cysteine. The reaction of L with Gd2O3 in water under reflux led to the formation of GdL. The coating of AuNPs with GdL was accomplished by direct addition of GdL to a solution of citrate-coated AuNPs. T1 measurements were carried out using an inversion recovery method with a variable inversion time at 64 MHz. MR and CT images of mice were obtained pre- and post- Au@GdL injection by tail vein with a 1.5 Tesla MR unit (GE Healthcare) and INVEON (Simens Medical Solutions) CT scanner respectively. The glioma cells were labeled with Lipofectamine by incubating with Au@GdL. Results Characterization of these particles by HRTEM, XRD, TGA, and ICP reveals that the size of Au@GdL is 14 nm with the loading of GdL on AuNPs reaching up to 2.9×103 GdL per AuNP. Extremely high molecular R1 relaxivity (105mM-1s-1) as well as X-ray attenuation has been accomplished with Au@GdL. The R1 relaxivity per [Gd] is as high as 17.9 mM-1s-1. Quantitatively, an extra contrast enhancement of about 15% seems to be contributed by 2 wt% of gadolinium immobilized on AuNPs. In vivo MR and CT images show clear contrast enhancement with Au@GdL, and the strong enhancement is observed in the liver. The accumulation of Au@GdL in Kupffer cells can be further demonstrated by both histological and TEM images. HU value of 700 μg Au@GdL/ 3×105 glioma cell gave an equivalent X-ray absorption as 10 mM of Ultravist. Conclusions Au@GdL exhibits macrophage-specific property, as demonstrated by histological and TEM images as well as CT and MR. Au@GdL could be used as bimodal MR/CT contrast agent and potential imaging tools to track cells
1785 Objectives: Radioimmunotherapy (RIT) using I-131 anti-CD20 rituximab is one of the promising therapeutic model for treatment of patient with non-Hodgkin’s Lymphoma (NHL). Although dosimetric approaches of low-dose I-131 rituximab imaging have been reported, there is no study of dosimetry with high-dose imaging in patient with NHL yet. In this study, we investigated the kinetic behavior and absorbed dose to bone marrow and whole body in RIT study with high-dose strategy using I-131 rituximab for NHL. Methods: I-131 rituximab with high-dose (5032 ~ 7400 MBq) was administrated to patients (n = 4) with NHL. Both anterior and posterior planar images of whole body were acquired simultaneously using a gamma camera (Scintron, MiE, Germany) with high-energy collimator at 5 min, 5hr, 24hr, 48hr, 72hr and 1 or 2 weeks post administration. Sampling venous blood was performed at the same points of imaging time. Prior to the administration, blank and transmission images were acquired using Co-57 sheet source, for attenuation correction, respectively. During the emission acquisition, several small vials filled with known activities of I-131 were placed beside patient, for correction of deadtime due to high-activity of I-131. The acquired anterior and posterior images were converted to geometric mean image for further analysis. Using the time-activity curves (TACs) of blood and whole body, the values of effect half-life of the blood and whole body time activity curves were calculated, and mean absorbed doses to bone marrow and whole body were estimated, respectively. Results: Deadtime on gamma images induced underestimation (~64%) of area under the TAC of whole body radioactivity. The radioactivity in blood and whole body decreased rapidly with time, and the residence time of blood and whole body were 27.5 ± 6.7 hr and 32.4 ± 7.8 hr, respectively. The values of mean absorbed dose were range from 0.26 to 0.93 Gy for bone marrow and from 0.12 to 0.39 Gy for whole body, respectively. The dominant contribution of dose was from bone marrow self dose (> 60%). Conclusions: Using the RIT protocol with high-dose I-131 rituxmab, quantitative estimation of absorbed dose to bone marrow and whole body was possible. This RIT strategy of I-131 rituxmab would be useful in monitoring treatment for NHL.
Abstract Background: The purpose of this study was to evaluate the biodistribution and safety of 64 Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64 Cu-labelled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer. Methods: PET images at 1, 24, and 48 hours after injection of 296 MBq of 64 Cu-NOTA-Trastuzumab were obtained on seven patients with breast cancer. The maximum standardized uptake value (SUV max ) was evaluated in the tumors, including the primary tumor and metastatic lesions. The mean SUV max (SUV mean ) was evaluated in the normal organs including the blood pool, liver, kidney, muscle, spleen, bladder, lung, and bone. In addition, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed by gathering the feedback of adverse reactions and safety-related issues within 1 month after 64 Cu-NOTA-Trastuzumab administration. Results: The overall values of SUV mean in each normal organ decreased with time on 64 Cu-NOTA-Trastuzumab PET images. The average values of SUV mean of the liver were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 hour, 24 hours, and 48 hours after injection. The average values of SUV mean of the blood were evaluated as 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 hour, 24 hours, and 48 hours after injection. The SUV max of HER2-positive tumors showed relatively higher than that of HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 hours after injection, respectively). Tumor to background ratios were calculated higher in the HER2-positive tumors than those of HER2-negative tumors. No adverse events related to 64 Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64 Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq). Conclusions: 64 Cu-NOTA-Trastuzumab showed specific uptake at the HER2-expressing tumors. It suggests that 64 Cu-NOTA-Trastuzumab can be a feasible monitoring tool for HER2 tumor status in the patients with breast cancer with safe. Trial registration: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr
1260 Objectives The aim of this study was to investigate the long-term outcomes of only lung metastasis in differentiated thyroid cancer (DTC) patients and the prognostic factors. Methods We retrospectively reviewed 110 DTC patients (M:F=31:79, Age;46±16) with only lung metastasis from 1988 to 2014; the median follow-up was 12.6 years. Patients were treated with radioactive iodine (RAI) after total thyroidectomy. Prognostic factors for overall survival were analyzed using Kaplan-Meier method and Cox proportional-hazard regression model. Results Of these 110 patients, 79 patients (71.8%) survived, and 31 patients (28.2%) were dead. Survival rates of 10- and 20- years were 72.4%, 67.3%. In univariate analysis, older age at diagnosis (≥45 years) (p=0.0002), less than 3 times of RAI (p=0.003), external radiotherapy (p=0.02), surgical treatment combined with external radiotherapy (p=0.02), iodine-avid with no improvement in whole body scan (WBS) (p=0.0008), and no uptake or multiple lung uptakes in WBS (p=0.03) showed poor prognosis for overall survival. In the multivariate analysis, older age at diagnosis (≥45 years) (hazard ratio [HR] 3.4, 95% confidence interval [CI] 1.2-9.4, p=0.02), less than 3 times of RAI (HR=2.8, 95% CI 1.2-6.7, p=0.02), and iodine-avid with no improvement in WBS (HR=4.8, CI 1.1-2.2, p=0.04) showed poor prognosis for overall survival. Conclusions Older age at diagnosis, less than 3 times of RAI, and iodine-avid with no improvement in WBS were prognostic factors for poor overall survival in DTC with only lung metastasis. RAI and WBS uptake assessment are essential for the treatment of DTC with lung metastasis.
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