p = 0.04.Number of planned pregnancies increased from 22% to 43%, p = 0.04.A non-significant increase in maternal weight gain (7.6-10.1 kg), gestational age (35-37 wks) and birth weight (2.58-2.78kg) was seen.Prevalence of women requiring LSCS fell from 39% to 29%.The number requiring lung Tx post pregnancy fell from 24% to 5%, p = 0.04.11women died [median time to death 8(1.1-16.9)yrs]; 64% in early cohort and 9% in latest, p = 0.03.Women with baseline FEV 1 < 60% were less likely to plan their pregnancy (15% vs. 53%, p = 0.003) with a higher % of premature deliveries and LBW babies.They had greater decline in FEV 1 and were more likely to die (73% vs.27%, p = 0.002).Women with pre-existing CFRD were less likely to plan, had lower weight gain (8 vs. 10.3 kg, p = 0.035), higher % premature deliveries (87% vs. 32%, p < 0.001) and LBW babies (60% vs. 26%, p < 0.001).Conclusion: With an aggressive MDT approach and specialist obstetric management, maternal outcomes have improved over time.Pre-existing CFRD and baseline FEV 1 < 60% however are associated with worse outcomes.Planning is essential to optimise outcomes for mother and baby.

Purpose Yttrium-90 (90Y) radioembolization dose planning requires balancing caution against toxicity with aggressiveness for efficacy, but each is impossible to predict based solely on morphologic imaging. We investigate the use of fusion MAA-sulfur colloid SPECT imaging to provide physiologic information relevant to dose calculation and outcomes. Materials and Methods A dual SPECT protocol was used with IA injection of technetium-99m (99mTc)-MAA (1 mCi) as a predictor of subsequent 90Y distribution, followed by IV 99mTc-sulfur colloid (5 mCi) as a biomarker for normal hepatic tissue. The SPECT data were co-registered and fused. A voxel based method was used to predict the 90Y radiation absorbed dose to functional hepatic tissue by calculation of 99mTc-MAA activity in voxels with 99mTc-sulfur colloid uptake. Similarly, the absorbed dose to tumor was predicted by calculation of 99mTc-MAA activity in voxels without 99mTc-sulfur colloid. Response (mRECIST) was recorded at 3 months, laboratory data were collected at 2, 4 and 8 weeks, and patients were followed until death. Retrospective SPECT based dosimetry was correlated with parameters of toxicity and efficacy and compared with standard parameters of dosimetry, administered activity, and whole liver absorbed dose. Results A total of 56 patients were included (32 M, 24 F; median age 62; 27 HCC, 29 CRC, 32 resin, 24 glass microspheres, median activity 2.02 GBq, median whole liver dose 70 Gray). Toxicity parameters (serum bilirubin, AST, ALT, albumin, hemoglobin, and platelets) correlated significantly with SPECT-based functional liver absorbed dose (median 38 Gy, p Conclusion Fusion MAA-Sulfur colloid SPECT is useful to predict tumor and functional liver absorbed dose, which correlate with efficacy and toxicity, and may be used in the future to develop an individualized physiology-based dose-planning method.

Radioembolization (RE) dose calculation is designed to maximize dose to targeted tumors while keeping hepatic parenchymal dose below 30 Gy. Repeated treatments carry theoretically higher risk of radiation-induced hepatic injury. We performed a retrospective safety analysis on patients who underwent repeated treatment. Since mid-2004, 247 patients have been treated with RE. Eight patients (5 M / 3 F; age range 51 - 71) were treated twice, all with SIR-Spheres (Sirtex, Lane Cove, Australia). They suffered from primary (cholangiocarcinoma n=2) or metastatic liver cancer (colorectal n=2, renal cell n=2, neuroendocrine n=1, leiomyosarcoma n=1). Five patients received whole liver treatment twice, one patient received right lobar treatment twice, and two patients received whole liver treatment first and lobar/segmental treatment the second time. The dose was calculated using the BSA method. Repeat treatments were dosed at 70-80% of calculated. The interval between treatments was 203 - 968 days. Standard follow-up consisted of clinical, laboratory, and imaging evaluation. Adverse events were graded using CTCAE Version 4.0. Two patients (cholangiocarcinoma, colorectal metastasis) died shortly after the second treatment (84 and 107 days). One patient had definite and one had suspected signs and symptoms of radiation induced liver disease (RILD) with up to grade 3 elevation of liver enzymes and bilirubin. One patient suffered grade 4 hepatic encephalopathy. Both patients had whole liver treatment twice (cumulative doses 3.36 and 2.66 GBq). The other 6 patients did well with only minor expected adverse events after receiving cumulative doses ranging from 2,41 to 3,88 GBq. One patient died due to disease progression 215 after the second treatment. The others are still alive with a median follow-up of 650 days (range 254 - 959 days). The risk of RILD appears to be elevated for repeated RE, but most patients escape injury. Risk factors need to be clarified.

Root cause analysis was performed on patients who suffered gastroduodenal ulceration after hepatic radioembolization. The aim was to identify the cause in individual cases and to identify risk factors in the treated population. Since mid-2004, 247 patients have been treated with yttrium-90 radioembolization for primary (n=90) or metastatic (n=157) liver cancer. A total of 278 treatments were performed using either SIR-Spheres (Sirtex, Lane Cove, Australia; n=197), or TheraSphere (MDS Nordion, Ottawa, Canada; n=81). Procedures included whole liver treatments with injection of microspheres into the common or proper hepatic artery (n=104), whole liver treatment with selective bilobar treatments in one session (n=45), or selective lobar/segmental treatment only (n=129). Anti-angiogenic agents were used by 88 patients. During microsphere administration, stasis of contrast occurred in 30 cases, all with SIR-Spheres. Standard follow-up consisted of clinical, laboratory, and imaging evaluation, up to at least 3 months. Logistic regression was used for risk assessment. Seven patients (4 M / 3 F; all metastatic disease treated with SIR-Spheres) developed a biopsy proven microsphere-induced gastroduodenal ulcer. Retrospective analysis of the intraprocedural images revealed the culprit vessel in 3 patients (accessory right gastric artery from the proximal left hepatic artery, cystic artery reconstituting the pancreaticoduodenal region feeding the right gastric artery, and a supraduodenal artery from the distal right hepatic artery). Use of anti-angiogenic agents, injection in the common or proper hepatic artery, and stasis were significant risk factors with odds ratios (and 95% confidence intervals) of 5.5 (1.0 - 28.8), 10.6 (1.3 - 89.2), and 61.8 (7.1 - 534.4), respectively. The occurrence of stasis was the only independent risk factor (p=0.002). The occurrence of stasis during injection of SIR-Spheres poses a significant risk factor for the development of gastroduodenal ulceration. Other risk factors include proximal injection in either the common or proper hepatic artery and the prior use of anti-angiogenic agents.

Methods currently used for 90Y radioembolization dose calculation are based on size of the tumors, liver, and/or patient. Actual dosimetry (and thus response and toxicity) reflects differential distribution of microspheres, a phenomenon for which a predictive model is needed. 1 mCi intraarterial 99mTc-labeled macroaggregated albumin (MAA) was administered at the time of preparatory angiography, followed by planar scintigraphy to calculate lung shunt fraction and SPECT imaging to depict intrahepatic distribution. Without moving the patient, 5 mCi intravenous 99mTc-labeled sulfur colloid (SC) was injected and the SPECT was repeated after a 5 minute delay. SC images were corrected for MAA cross-talk, and images were registered to form a fusion MAA-SC dataset. Thresholds were applied to characterize each voxel as positive for MAA uptake, for SC uptake, for both, or for neither. Voxels showing uptake of only MAA were defined as tumor, uptake of only SC as background liver, and uptake of both as marginal liver. Total volumes and radiation doses to tumor, to background liver, and to marginal liver were calculated and correlated with survival. Fusion datasets and minimum 3 month follow-up were acquired for 44 patients with various primary or metastatic hepatic neoplasms, with survival of 142 ± 203 days (median ± SD, range 34-1043). Independent of cell type, multivariate analysis revealed positive correlation of survival with tumor dose, with ratio of tumor dose to marginal liver dose, and with marginal liver dose, but a negative correlation with total marginal liver volume. Patients with tumors that were more hypervascular and thus received higher radiation doses survived longer. Survival was poorer for patients with larger volumes of marginal liver, i.e. those whose functional liver tissue received substantial radiation. Fusion scintigraphic imaging after intraarterial MAA and intravenous SC administration yields predicted differential dosimetry, which is correlated with patient survival. This methodology may enable improved personalized dose calculations and prognostication.

aNuclear Medicine Department, Glasgow Royal Infirmary, UK bNuclear Medicine Department, Stanford University Medical Centre, California, USA Abstracts for the Autumn Meeting of the British Nuclear Medicine Society Cambridge, UK, 4–5 September 2006

PURPOSES To evaluate quantitative air trapping measurements in children with mild cystic fibrosis (CF) lung disease during a 1-year, double-blind, placebo-controlled, recombinant human deoxyribonuclease (rhDNase) [dornase alfa] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT (HRCT) scans of the chest. MATERIALS AND METHODS Twenty-five children with CF randomized to either daily rhDNase or placebo aerosol were evaluated at baseline, and at 3 months and 12 months by spirometer-triggered HRCT and spirometry. Outcome variables were percentage of predicted FVC, FEV1, and forced expiratory flow, midexpiratory phase (FEF(25-75%)); total and subcomponent visual HRCT scores; and quantitative air trapping measurements derived from chest HRCT images. RESULTS At baseline, there were no statistical differences between groups in any of the variables used as an outcome. After 3 months of treatment, both groups had improvements in percentage of predicted FEV1 and FEF(25-75%), and total HRCT visual scores. In contrast, the rhDNase group had a 13% decrease in quantitative air trapping from baseline (severe air trapping [A3]), compared to an increase of 48% in the placebo group (p = 0.023). After 12 months, both groups had declines in percentage of predicted FVC and FEV1, but the rhDNase group retained improvements in percentage of predicted FEF(25-75%) and quantitative air trapping. The mucus plugging and total HRCT visual scores were also improved in the rhDNase group after 12 months of treatment, with and without significant differences between groups (p = 0.026 and p = 0.676). Quantitative air trapping (A3) remained improved in the rhDNase group (- 15.4%) and worsened in the placebo group (+61.3%) with nearly significant differences noted between groups (p = 0.053) after 12 months of treatment. CONCLUSIONS Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.

Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium ((90)Y; 15 mCi/m(2))/(111)In (5 mCi)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T(1/2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. (90)Y/(111)In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of (90)Y-DOTA-biotin in this format is warranted.

Up to 70% of heart attacks are thought to be caused by vulnerable plaque in arterial walls. We report on the first preclinical tests of an intravascular imaging detector to identify vulnerable coronary artery plaques. The detector identifies plaque by sensing beta emission from radiotracers, which bind to the vulnerable plaque. The detector design consists of a bundle of six 7 mm long scintillating fibers each fused to a 1.5 m plastic fiber. The scintillating fibers are offset from each other longitudinally by 6 mm and arranged spirally around a guide wire in the center of the catheter. To demonstrate the detection performance of this probe, excised arteries of transgenic mice were scanned using a single fiber version of the probe. The distal end of the probe was scanned over the arteries using a micrometer, and 2D images of the beta activity in the arteries were made. The images were later superimposed on autoradiographic images acquired from the same arteries to confirm the uptake in the plaque. The beta imaging probe was able to detect beta labeled plaque and a high degree of correlation with the autoradiography results validated the concept of using such a device to identify vulnerable plaque in-vivo. The future development of the detector will include additional in-vivo studies with animal models, and further development of the intravascular probe for improved sensitivity and miniaturization.

Purpose: The authors describe the variability of Tc-99m exametazime-labeled leukocyte distribution as a function of the relative frequency of white cell types in the labeled blood.Materials and Methods: A 76-year-old man who was hospitalized with fever and possible postoperative osteomyelitis underwent scintigraphic imaging with Tc-99m exametazime-labeled leukocytes.Results: The white cell scan excluded any discrete focus of infection and revealed diffuse involvement of the lymph nodes and skin. The pathologic diagnosis was angioimmunoblastic T-cell lymphoma. The atypical infiltrates seen on the white cell scan can be explained by the severe eosinophilic blood count on the day of leukocyte labeling (total leukocyte count: 8,100 cells/mul with 63% neutrophils, 8.9% lymphocytes, and 22.2% eosinophils).Conclusion: In the labeling of the leukocyte moiety, a higher presence of any leukocyte subpopulation will modify the biodistribution and thus the image interpretation.