A new technique to evaluate experimental acute pulmonary oedema using giant unilamellar liposomes

Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 Curcumin is a safe and effective anticancer molecule, but its therapeutic potential has been limited by poor bioavailability. We synthesized a curcuminoid, N-{2[3,5-bis-(2-fluorobenzylidene)-4-oxo-piperidin-1-yl]-ethyl}-6-hydrazinonicotinamide (EFAH) as an antiproliferative derivative amenable to Tc-99m radiolabeling. Cell proliferation assays showed that EFAH was significantly more potent than curcumin in lung adenocarcinoma H441 cells. Tc-99m-labeling was followed by Radio-reverse phase-HPLC using 5-to-15% acetonitrile gradient over 20 min (RT 11.2 min, 1 ml/min). Tc-99m-EFAH was injected in nude rats carrying xenograft H441 tumor. Planar whole body image acquisitions and biodistribution (24 h) were performed. The labeled compound accumulated in liver (2.6% ID/g), and was cleared by hepatobiliary route. The tumor accumulated 0.023%ID/g. High-performance liquid chromatography of urine collected 30 min post-injection showed unmodified Tc-99m-EFAH. This study visually shows the distribution of a synthetic curcuminoid for the first time, and reinforces the previously-demonstrated effectiveness of 3,5-bis-(2-fluorobenzylidene)-4-piperidone in colon cancer. The approach enables “image-guided therapeutics.” doi:10.1016/j.nucmedbio.2010.04.095 Radiolabelled short neuropeptide Y derivatives with bifunctional chelators for breast cancer Patricia Antunes1, Paula Raposinho, I. Santos COSTD38-WG3, Instituto Tecnológico e Nuclear, Estrada Nacional 10, 2686-953 Sacavém, Portugal Breast cancer is still one of the most prevalent malignant diseases among women. Despite the efficacy of surgery for treating early detected and localized disease, serious repercussions include physical and psychosocial problems. Radiotherapy and chemotherapy are available, but their effectiveness is limited by severe side effects. Selective targets and simple tools to localize and treat tumours at an early stage of development are necessary. Lately, neuropeptide Y-receptors (NPY) gained attention as their incidence and density in breast cancer and its metastasis are high, switching the NPY receptor subtype expression from Y2 and Y1 in healthy tissue to Y1 in neoplastic tissue. [1] Moreover, the discovery of a small neuropeptide Y1receptor selective agonist to target human breast cancer gave a new important input on the research on the detection of cancerous tissues metastases at an earlier time point. [1] Based on its structure: [Pro30, Nle31, Bpa32, Leu34]NPY (28-36), two types of bifunctional chelators were coupled and the pharmacological profile of their radiocomplexes were outlined.

Reference [1] Denise Z, Ilka B, Diana L, Annette GBS. First selective agonist of the neuropeptide Y1-receptor with reduced size. J Pept Sci 2009;15:856-66. doi:10.1016/j.nucmedbio.2010.04.124 Evaluation of acute non-cardiogenic experimental pulmonary oedema using giant unilamellar liposomes Ana Cristina Santosa, C.M. Matosa, S.L. Perestreloa, M.A. Silvaa, F.J. Borgesa, L. Ganob, M. Nevesb, B. Oliveirosa a Biophysics/Biomathematics Institute, FMUC-IBILI, 3000-548 Coimbra, Portugal b Nuclear Technological Institute, Sacavém, Portugal Pulmonary oedema plays an important role in respiratory insufficiency. An experimental pulmonary oedema has been induced in Wistar rats with alphanaphtylthiourea (60 mg/kg of body weight, ip), solubilized in trioleine, which increases lung vascular permeability. Our thermolabile giant liposomes (GUVs, 37°C; 15–30 μm) [DSPC (diestearoylphosphatidylcholine)/EPG

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(phosphatidylglycerol)/CHOL (cholesterol), 60%/10%/30%, respectively] aim to detect this induction, by a non-surgical protocol. An encapsulated hydrosoluble and diffusible radiopharmaceutical (99mTc-DMSA, intravenous injection) will equilibrate with the interstitial water space. The tracer's disappearance rate will correlate with the dimension of this space. 99mTc-DTPA was used as counterproof (hydrosoluble but nondiffusible). Two groups of animals (DMSA and DTPA), subdivided in two subgroups (control and oedema) were organized to administer cooled radiolabelled GUVs in the femoral vein. Statistical analysis has been performed using STATISTICA (version 8). Biodistribution studies were done, showing an effective pulmonary oedema induction 4 hours after alphanaphtylthiourea injection, and organ samples (e.g., lung, kidney, liver, heart, blood) were collected. With 99mTc-DMSA GUVs, there are statistical significant differences between control and oedema [lung (P=.036) and kidney (P=.016)], while for 99mTc-DTPA GUVs, P is .835 and .531, respectively. Comparing DMSA and DTPA for rats with oedema, there are always significant statistical differences (e.g., lung, P=.001; kidney, P=.008). The proposed methodology is easy to perform, noninvasive, reproducible and less expensive and may contribute to a fast and efficient diagnosis of this pathology. doi:10.1016/j.nucmedbio.2010.04.056 A new technique to evaluate experimental acute pulmonary oedema using giant unilamellar liposomes Ana Cristina Santosa, C.M. Matosa, M.A. Silvaa, S.L. Perestreloa, F.J. Borgesa, T. Almeidaa, N. Ferreiraa, L. Ganob, M. Nevesb, B. Oliveirosa a Biophysics/Biomathematics Institute, FMUC-IBILI, Coimbra, Portugal b Nuclear Technological Institute, Sacavém, Portugal Pulmonary edema is a main cause for respiratory insufficiency. A precise, sensitive and reproducible method to determine pulmonary water space has not yet been proposed, being noninvasive, less expensive and easily performed. Our thermolabile giant liposomes (GUVs, 37°C, 15–30 μm) [DSPC (diestearoylphosphatidylcholine)/EPG (phosphatidylglycerol)/CHOL (cholesterol), 60%/10%/ 30%, respectively] aim to evaluate this water space. A noncardiogenic experimental pulmonary œdema (Wistar rat), using monocrotaline (80 mg/kg of body weight, sc), was produced and detected through femoral injection of our cooled GUVs. 99mTc-DMSA (hydrossoluble and diffusible), encapsulated in the GUVs, was delivered into lung capillaries, and equilibrated with the interstitial water space. 99mTc-DTPA was selected as counterproof (hydrossoluble but nondiffusible). The animals were divided into 8 groups (4 and 48 hours, 1 to 6 weeks) to administer radiolabelled GUV's, both for DMSA and DTPA. Each animal has been used as its own control. Statistical analysis was performed using STATISTICA (version 8). Homemade software based in IDL language has been used for image processing. 99mTc-DMSA-GUVs effectively enabled pulmonary œdema detection along time (Pb.001, thorax ROI between control and œdema), opposing to 99mTc-DTPA-GUVs, as expected (P=.809, thorax ROI between control and œdema along time). Pulmonary edema is very slowly but effectively induced by monocrotaline, being early detected by our radiolabelled GUVs with DMSA. This could contribute for the diagnosis of this pathology in an initial phase. doi:10.1016/j.nucmedbio.2010.04.057 Bimodal ligand-tailored hyperbranched polyglycerols for magnetic resonance and SPECT imaging studies Katayoun Saatchia, Peter Soemaa, Rajesh K. Kainthanb, Donald E. Brooksb, Urs O. Häfelia a Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver BC, Canada V6T 1Z3 b Centre for Blood Research, Life Sciences Centre, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC, Canada V6T 1Z3