BACKGROUND: 177 Lu-(DOTA0,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 kidneyabsorbed 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.

The purpose of this study was to develop multimodality SPECT/ MRI contrast agents for sentinel lymph node (SLN) mapping in vivo. Methods: Nanoparticles with a solid iron oxide core and a polyethylene glycol coating were labeled with 99m Tc. The labeling efficiency was determined with instant thin-layer chromatography and magnetic separation. The stability of the radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) was verified in both sterile water and human serum at room temperature 6 and 24 h after labeling. Five Wistar rats were injected subcutaneously in the right hind paw with 99m Tc-SPIONs (25-50 MBq, ;0.2 mg of Fe) and sacrificed 4 h after injection. Two animals were imaged with SPECT/MRI. All 5 rats were dissected; the lymph nodes, liver, kidneys, spleen, and hind paw containing the injection site were removed and weighed; and activity in the samples was measured. The microdistribution within the lymph nodes was studied with digital autoradiography. Results: The efficiency of labeling of the SPIONs was 99% 6 h after labeling in both water and human serum. The labeling yield was 98% in water and 97% in human serum 24 h after labeling. The SLN could be identified in vivo with SPECT/MRI. The accumulation of 99m Tc-SPIONs (as the percentage injected dose/g [%ID/g]) in the SLN was 100 % ID/g, whereas in the liver and spleen it was less than 2 %ID/g. Digital autoradiography images revealed a nonhomogeneous distribution of 99m Tc-SPIONs within the lymph nodes; nanoparticles were found in the cortical, subcapsular, and medullary sinuses. Conclusion: This study revealed the feasibility of labeling SPIONs with 99m Tc. The accumulation of 99m Tc-SPIONs in lymph nodes after subcutaneous injection in animals, verified by SPECT/MRI, is encouraging for applications in breast cancer and malignant melanoma. The sentinel lymph node (SLN) is defined as the first regional lymph node receiving lymphatic drainage from a malignant tumor (1) and the first node to which metastatic cells are likely to anchor. Therefore, accurate detection and characterization of the SLN is of major importance for cancer staging and for the choice of therapy in patients with breast cancer and malignant melanoma. The current gold standard relies on lymphoscintigraphy after intradermal injection of radiolabeled colloids and blue dye to intraoperatively identify the SLN by dissection and histopathologic examination (2). The radiopharmaceuticals most frequently used for SLN imaging are 99m Tc-labeled colloids and macromolecules such as trisulfide, dextran, and human serum albumin (3-5). The current technique, however, is limited because of the nonspecificity of the tracer and the lack of anatomic information in scintigraphic images. Preoperative planning and identification of the SLN often rely on the experience of the surgeon.We propose combining information from high-resolution MRI and high-sensitivity SPECT images to provide more accurate and less invasive identification of the SLN before surgery. The use of radioactivity would help to ...

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This feasibility study demonstrates 90 Y quantitative bremsstrahlung imaging of patients undergoing high-dose myeloablative 90 Y-ibritumomab treatment. Methods: The study includes pretherapy 111 In SPECT/CT and planar whole-body (WB) imaging at 7 d and therapy 90 Radi oimmunotherapy is established for the treatment of relapsing follicular or transformed B-cell lymphomas. Two radioimmunoconjugates, 90 Y-ibritumomab (Zevalin; Spectrum Pharmaceuticals) and 131 I-tositumomab (Bexxar; GlaxoSmithKline), were approved. A dose-response relationship can be inferred from several observations (1,2), and the best clinical results published have made use of myeloablative radioimmunotherapy (3).In standard 90 Y-ibritumomab treatments, administered activity is based on patient weight. For high-dose ibritumomab studies involving bone-marrow stem-cell support, an accurate dosimetry is required. The organs at risk in these studies are the liver, kidneys, and lungs. To maximize the therapy effect, it is important to not exceed the maximumtolerable dose (MTD). We have an ongoing clinical absorbed dose-escalation study to determine MTD for the liver based on a pretherapy dose planning. The pretherapy dosimetry is performed by imaging with 111 In-labeled ibritumomab to predict the 90 Y activity required for treatment. There is also a need to monitor the actual treatment for dose verification. A mixture of 111 In-and 90 Y-labeled ibritumomab could allow for imaging; however, this method has potential drawbacks. First, any labeling instability produces free-circulating 111 In, which gives nonrepresentative image information. Second, 90 Y bremsstrahlung may contaminate the 111 In energy windows, leading to errors in the activity quantification. Third, an 111 In-ibritumomab kit can be costly. If quantitative 90 Y bremsstrahlung imaging is feasible, such a study could confirm both targeting and delivery of the prescribed absorbed dose.Previously, we have experimentally investigated quantitative bremsstrahlung SPECT and planar whole-body (WB) imaging (4,5). To our knowledge, no studies have been performed on quantitative bremsstrahlung imaging of patients given radiolabeled monoclonal antibody. In this work, the feasibility of quantitative bremsstrahlung imaging to verify predicted absorbed doses was investigated for SPECT and WB imaging using data from our escalation study. That study includes a pretherapy study with 111 Inlabeled ibritumomab in which SPECT/CT and WB imaging allow for a comparison of quantitative 90 Y with quantitative 111 In imaging. MATERIALS AND METHODS Patients and Study ProtocolIn this work, 3 patients were evaluated (2 men [ages, 74 and 57 y; weights, 74 and 79 kg] and 1 woman [age, 71 y; weight, 70 kg]). The organ at risk was the liver, because bone-marrow stemcell support was given. All patients received 300 MBq of 111 Inibritumomab in the pretherapy study, followed by SPECT/CT and WB imaging on 7 occasions (at 1, 24, 48, 72, 144, 166, and 192 h after imaging). The SPECT/CT data determined the necessary therap...

A new method for absorbed-dose assessment in radionuclide therapy is presented in this paper. The method is based on activity quantification by the conjugate-view methodology, applied to serial whole-body, anterior-posterior, scintillation-camera scans. The quantification method is an extension of previous studies, and includes separate corrections for attenuation, scatter, and overlapping organs. Further development has now been undertaken to take into account the capabilities of new dual-head camera systems with a built-in X-ray tube for anatomical imaging. Furthermore, the modeling of time-activity data is included, and dosimetric calculations based on the formalism by the Medical Internal Radiation Dose (MIRD) committee. To streamline absorbed-dose assessments for a large number of patient studies, the programs for quantification, image registration, and absorbed-dose calculations have been embedded in an envelop program termed LundADose, where calculations, to a great extent, are performed automatically. Evaluation of the whole-body activity quantification is performed for patients undergoing radioimmunotherapy by monoclonal antibodies labeled with (111)In or (90)Y.