Prospective SPECT-CT Organ Dosimetry-Driven Radiation-Absorbed Dose Escalation Using the In-111 (111In)/Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) Theranostic Pair in Patients with Lymphoma at Myeloablative Dose Levels.

PURPOSE: We prospectively evaluated the feasibility of SPECT-CT/planar organ dosimetry-based radiation dose escalation radioimmunotherapy in patients with recurrent non-Hodgkin's lymphoma using the theranostic pair of 111In and 90Y anti-CD20 ibritumomab tiuxetan (Zevalin®) at myeloablative radiation-absorbed doses with autologous stem cell support. We also assessed acute non-hematopoietic toxicity and early tumor response in this two-center outpatient study. METHODS: 24 patients with CD20-positive relapsed or refractory rituximab-sensitive, low-grade, mantle cell, or diffuse large-cell NHL, with normal organ function, platelet counts > 75,000/mm3, and <35% tumor involvement in the marrow were treated with Rituximab (375 mg/m2) weekly for 4 consecutive weeks, then one dose of cyclophosphamide 2.5 g/m2 with filgrastim 10 mcg/kg/day until stem cell collection. Of these, 18 patients with successful stem cell collection (at least 2 × 106 CD34 cells/kg) proceeded to RIT. A dosimetric administration of 111In ibritumomab tiuxetan (185 MBq) followed by five sequential quantitative planar and one SPECT/CT scan was used to determine predicted organ radiation-absorbed dose. Two weeks later, 90Y ibritumomab tiuxetan was administered in an outpatient setting at a cohort- and patient-specific predicted organ radiation-absorbed dose guided by a Continuous Response Assessment (CRM) methodology with the following cohorts for dose escalation: 14.8 MBq/kg, and targeted 18, 24, 28, and 30.5 Gy to the liver. Autologous stem cell infusion occurred when the estimated marrow radiation-absorbed dose rate was predicted to be <1 cGy/h. Feasibility, short-term toxicities, and tumor response were assessed. RESULTS: Patient-specific hybrid SPECT/CT + planar organ dosimetry was feasible in all 18 cases and used to determine the patient-specific therapeutic dose and guide dose escalation (26.8 ± 7.3 MBq/kg (mean), 26.3 MBq/kg (median) of 90Y (range: 12.1-41.4 MBq/kg)) of ibritumomab tiuxetan that was required to deliver 10 Gy to the liver. Infused stem cells engrafted rapidly. The most common treatment-related toxicities were hematological and were reversible following stem cell infusion. No significant hepatotoxicity was seen. One patient died from probable treatment-related causes-pneumonia at day 27 post-transplant. One patient at dose level 18 Gy developed myelodysplastic syndrome (MDS), 4 patients required admission post-90Y RIT for febrile neutropenia, 16/18 patients receiving 90Y ibritumomab tiuxetan (89%) responded to the therapy, with 13 CR (72%) and 3/18 PR (17%), at 60 days post-treatment. Two patients had progressive disease at sixty days. One patient was lost to follow-up. Median time to progression was estimated to be at least 13 months. MTD to the liver is greater than 28 Gy, but the MTD was not reached as the study was terminated due to unexpected discontinuation of availability of the therapeutic agent. CONCLUSIONS: Patient-specific outpatient 90Y ibritumomab tiuxetan RIT with myeloablative doses of RIT up to a targeted 30.5 Gy to the liver is feasible, guided by prospective SPECT/CT + planar imaging with the theranostic pair of 111In and 90Y anti-CD20, with outpatient autologous stem cell transplant support. Administered activity over 5 times the standard FDA-approved activity was well-tolerated. The non-hematopoietic MTD in this study exceeds 28 Gy to the liver. Initial tumor responses were common at all dose levels. This study supports the feasibility of organ dosimetry-driven patient-specific dose escalation in the treatment of NHL with stem cell transplant and provides additional information on the radiation tolerance of the normal liver to radiopharmaceutical therapy.

Pilot study using PET/CT as a novel, noninvasive assessment of disease activity in inflammatory bowel disease.

BACKGROUND: A pilot study was performed investigating the possibility that positron emission tomography (PET) activity using 18-fluorodeoxyglucose (FDG) with nearly simultaneous computerized tomography (CT) for anatomic accuracy would identify regions of active inflammation in both ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Prospective clinical data was collected in 12 patients experiencing an exacerbation of their inflammatory bowel disease; 7 with CD and 5 with UC. A PET/CT scan (GE Discovery LS PET/CT scanner) was performed in all patients. Twenty patients undergoing PET/CT because of solitary pulmonary nodules served as controls. We graded the small bowel and 4 colon regions (ascending, transverse, descending, and rectosigmoid) with PET activity scores assigned to each region based on the amount of FDG uptake using the liver as the reference organ. RESULTS: In UC patients, PET activity was seen in 13 of 24 (52%) regions. There was high (23 of 24; 95.8%) correlation between PET activity and disease activity as determined by colonoscopy, disease activity indices, and radiology. In patients with CD, PET activity was seen in 19 of 32 (59.4%) regions. Again, there was a high (26 of 32; 81.3%) correlation between PET activity and clinical disease activity. Of the 20 controls, significant PET activity (Grades 2 and 3) was seen in only 2 of 100 regions (2%). CONCLUSIONS: We found that PET activity correlated well with active inflammation in both UC and CD, suggesting that this may be a noninvasive method of identifying disease activity in patients with inflammatory bowel disease.

Influence of reconstruction iterations on 18F-FDG PET/CT standardized uptake values.

UNLABELLED: The goal of this study was to evaluate the effect on the average standardized uptake value (avgSUV) and maximum standardized uptake value (maxSUV) of changing the number of iterations in the reconstruction process on studies acquired with PET/CT. METHODS: Data from 50 human tumors were acquired on a PET/CT scanner, using the CT portion for attenuation correction. Reconstruction was performed using the 2-dimensional reconstruction method of ordered-subsets expectation maximization (OSEM) with 28 subsets and with 1, 2, 3, 4, 5, 10, 20, and 40 iterations. The standardized uptake value (SUV) of the studies was analyzed by positioning a region of interest tightly around the tumor and reproducing the same area on all same-study iterations for SUV measurements. RESULTS: The differences in mean avgSUV and mean maxSUV were statistically different across different iteration groups. SUV data demonstrated that the avgSUV measurements have the most significant differences between 1 versus 2 iterations and 2 versus 3 iterations. The P values for these comparisons were less then 0.001. For maxSUV, all differences had P values less than 0.001. There also was a systematic increase in the SUVs as the number of iterations increased. The avgSUV increased at early iterations (less than 5), with just 50%-60% increasing after 5 iterations. However, maxSUV increased systematically at early iterations, and this trend continued as the number of iterations increased. CONCLUSION: The OSEM algorithm converges sooner for avgSUV than for maxSUV. The likely reason is that avgSUV depends on low-frequency features that are recovered with fewer iterations. The differences in maxSUV were likely due to noise, which increased with the number of iterative updates, and to increased resolution and recovery of high-frequency features (i.e., tumor heterogeneity) with a larger number of iterations. Factors that determine the quantitative accuracy of iterative reconstruction may have played an additional role. Given the continued change in maxSUV with iterations, great care must be taken in selecting the number of iterative updates when using it to assess tumors and their response to chemotherapy and radiation therapy. Because 2-5 iterations with 8-28 subsets are being used in clinical settings, these data are pertinent when comparing the SUVs of a tumor before and after therapy.

SPECT imaging of apical hypertrophic cardiomyopathy.

Apical hypertrophic cardiomyopathy, common in Japan, is characterized by a spade-like configuration of the left ventricle on contrast angiography. The condition is identified by giant negative T waves in the precordial echocardiographic leads, no intraventricular pressure gradient, and mild symptoms. A case showing the typical scintigraphic and cardiac echocardiographic findings of apical hypertrophic cardiomyopathy is presented.