Comparisons of dosimetric approaches for fractionated radioimmunotherapy of non-Hodgkin lymphoma.

AIM: The aim of this study was to compare different dosimetric approaches on therapy naïve patients enrolled in a multicentre fractionated radioimmunotherapy trial, to determine which methodological approach correlates with bone marrow toxicity. METHODS: Twenty-height non-Hodgkin lymphoma patients were treated with one or two fractions of 90Y-Ibritumomab-Tiuxetan (11.1 MBq/kg) 8 to 12 weeks apart in four different institutions. Quantitative imaging with 111In-Ibritumomab-Tiuxetan (185 MBq) was performed at 0, 1, 4 and 7 days after infusion, starting two weeks before the therapeutic administration. A whole-body (WB) CT scan was also acquired prior to the 111In-Ibritumomab injection, for attenuation correction purposes and was segmented to derive patient-specific organ masses. All dosimetry processing was centralized in a single institution. The first method (M_2D) was based on geometric mean WB scans, corrected for attenuation, scatter and organs superposition. The second method (M_2.5D) was based on the computed assisted matrix inversion approach and used segmented CT scans. The third method (M_3D) used iterative reconstruction of tomographic scans, corrected for attenuation, scatter and collimator response. Absorbed doses were estimated for lungs, liver, kidneys and spleen using MIRD S values adjusted for organ masses. Bone marrow (BM) absorbed doses were evaluated according to imaging methods (3) and compared to blood-based approaches. RESULTS: For some patients, organ masses such as liver or spleen significantly differed from male/female reference masses, whereas lungs and kidneys masses were relatively constant. Except for lungs, absorbed doses estimated by M_2D were higher than those from M_2.5D and these, in turn, were higher that those calculated from M_3D (Wilcoxon P<8.6e-4). Median organ absorbed dose estimates were equivalent for both fractions except for the spleen. In fact, spleen absorbed doses for the second fraction were lower than those for the first fraction, regardless of the approach. Possible explanations are that patient spleen masses were kept constant for analysis of both fractions and/or that spleen uptake was lowered after the first fraction. Estimation of BM absorbed doses from blood sampling was unable to predict platelet toxicity, but image-based methods performed better. Additionally, for most organs, the absorbed dose delivered by the first fraction could predict that delivered by the second fraction. CONCLUSION: These results confirm that different acquisition/processing protocols will lead to statistically different absorbed doses. Additionally, image-based dosimetric approaches are needed in order to correlate absorbed dose to bone marrow toxicity.

Keratinocyte growth factor improves alterations of lung permeability and bronchial epithelium in allergic rats.

Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increase lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, the current authors evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma. KGF (1 mg x kg(-1)) was administered intravenously before the last ovalbumin (OVA) challenge in sensitised rats. Permeability was assessed by the leak of radiolabelled albumin from the alveolar and systemic compartments. Histopathological analysis was also performed. Treatment with KGF decreased the leak of both markers and decreased the level of extravascular lung water in sensitised rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage fluid but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and the expression of the intercellular junction proteins beta-catenin and zonula occludens protein-1. In conclusion, keratinocyte growth factor administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.

Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of osteomyelitis in the diabetic foot.

OBJECTIVES: The diagnosis of osteomyelitis in patients with diabetic foot is difficult both clinically and radiologically. An early diagnosis is crucial to optimize therapeutic strategy. Among the diagnostic methods currently used, scintigraphy with ex-vivo labelled white blood cells is the gold standard, but cannot be performed in all centers; therefore 67Gallium citrate (67Ga) imaging in combination with a bone scintigraphy is still widely used. METHOD: The results of imaging 24 diabetic patients with 31 suspected osteomyelitic lesions using the antigranulocyte Fab' fragment (Sulesomab or LeukoScan or immunoscintigraphy) were prospectively compared with results from the bone scan coupled with 67Ga. The diagnosis of osteomyelitis was confirmed by either biopsy or follow-up, radiological imaging and clinical outcome. RESULTS AND CONCLUSION: Sulesomab correctly identified 12 of 18 osteomyelitic lesions while 67Ga was able to detect only 8 of 18. Therefore the sensitivity is 67% for Sulesomab and 44% for 67Ga. Among the 13 non-osteomyelitic lesions imaging with Sulesomab was able to rule out infection in 11 cases and 67Ga in 10 cases. The specificity is therefore 85% for Sulesomab and 77% for 67Ga. Image interpretation for Sulesomab in this group of patients is occasionally suboptimal when imaging is performed at 3 hours post injection. High vascular background in the early images may obscure infection especially in small bones. Practically, scintigraphy with Sulesomab is fast and simple due to ease of labeling, no ex-vivo handling of blood, low radiation and provides rapid diagnosis. The diagnosis of osteomyelitis obtained by the antibody fragment scintigraphy influences the management (guided biopsy) and therapy. In several patients, imaging with Sulesomab was able to rule out osteomyelitis, helping to avoid useless antibiotic therapy and its associated side effects.

A study of the behaviour of cobalt chloride during the labelling of leukocytes with 99Tcm-HMPAO stabilised in vitro by the addition of cobalt chloride solution.

The method described by Weisner et al. for stabilizing 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) with cobalt chloride hexahydrate solution is the most promising developed to date. The aim of our work was to study the behaviour of cobalt during the labelling of leukocytes with 99Tcm-HMPAO stabilized in vitro using this method. Three parallel labellings were carried out using six blood samples taken from polycythaemic patients. The first set of labellings was performed using 99Tcm-HMPAO, the second set using 99Tcm-HMPAO stabilized with cobalt chloride hexahydrate solution "spiked' with 57Co-chloride, and the third set using 57Co-chloride solution alone. Measurements of radioactivity content were made on the leukocyte pellets after washing at five time points post-labelling (t = 0, 30 min, 1 h, 2 h and 4 h). The data show that leukocytes do not retain cobalt during labelling with stabilized 99Tcm-HMPAO. Studies carried out in parallel demonstrated that the presence of cobalt in the cell-labelling medium had no effect on cell viability.