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Gamma Imager

Publications

Oncology

Chemin C, Péan JM, Pape AL, Delbos JM, German-Fattal M, Wüthrich P, Couvreur P: Biodistribution and anticancer activity of a new vinca alkaloid encapsulated into long-circulating liposomes J Liposome Res. July (2009)

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Abstract
S12363 is a potent therapeutic agent with a strong in vitro activity against a variety of tumor types but also a high in vivo toxicity. Loading of this drug into long-circulating liposomes is expected to enhance its therapeutic index. Pharmacokinetics of liposomal S12363 showed that circulating S12363 was entrapped into liposomes until 24 hours after intravenous injection in mice. The liposomal formulation significantly increased the plasma concentration, half-life, and AUC and decreased the plasma clearance rates and volume of distribution of S12363. Liposome extravasation was evaluated with two tumor models by both microscopic analysis and liposome radiolabeling. Liposome accumulation was much more important in the case of B16 melanoma, compared to H460 tumor, with both inoculated subcutaneously and with comparable size. H460 tumor was also inoculated into the lung. The tumor localization did not influence liposome accumulation into the tissue. The liposomal formulation injected into mice bearing B16 melanoma allowed a 10-fold accumulation of S12363 into the tumor interstitium, as compared to the solution. Bioluminescence data, supported by the survival curves of the animals, showed that S12363-liposomes were able to significantly restrict B16 melanoma progression and increase mice survival.

Sancey L, Ardisson V, Riou LM, Ahmadi M, Marti-Batlle D, Boturyn D, Dumy P, Fagret D, Ghezzi C, Vuillez JP.: In vivo imaging of tumour angiogenesis in mice with the alpha(v)beta (3) integrin-targeted tracer (99m)Tc-RAFT-RGD Eur J Nucl Med Mol Imaging 34(12):2037-47 August (2007)

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Abstract
Purpose: The molecular imaging of tumour neoangiogenesis currently represents a major field of research for the diagnostic and treatment strategy of solid tumours. Endothelial cells from tumour neovessels overexpress the avß3 integrin, which selectively binds to Arg-Gly-Asp (RGD)-containing peptides. We evaluated the potential of the novel radiotracer 99mTc-RAFT-RGD for the non-invasive molecular imaging of avß3 integrin expression in mice models of tumour development. Methods 99mTc-RAFT-RGD, 99mTc-cRGD (specific control) and 99mTc-RAFT-RAD (non-specific control) were injected intravenously to mice bearing B16F0 or TS/A-pc tumours. In vivo whole-body tomographic imaging and post-mortem biodistribution studies were performed 60 min following tracer injection. Adjacent tumour slices were used to compare the localisation of neovessels from immunostaining and the pattern of 99mTc-RAFT-RGD uptake from autoradiographic ex vivo imaging. Results: Biodistribution studies indicated that 99mTc-RAFT-RGD tumour uptake was significantly higher than that of 99mTc-RAFT-RAD in B16F0 (2.4±0.5 vs 1.0±0.1%ID/g, respectively) and in TS/A-pc tumours (2.7±0.8 vs 0.7±0.1%ID/g, respectively). Immunohistochemical and autoradiographic studies indicated that 99mTc-RAFT-RGD intratumoural uptake preferentially occurred in angiogenic areas. Tomographic imaging allowed tumour visualisation following injection of 99mTc-RAFT-RGD and 99mTc-cRGD with similar tumour-to-contralateral muscle (T/CM) ratios in B16F0 and in TS/A-pc tumours whereas 99mTc-RAFT-RAD T/CM ratios did not allow tumour imaging. In accordance with the higher level of avß3 integrin expression on TS/A-pc tumours than on B16F0 tumours as determined from western blot and immunoprecipitation analyses, the 99mTc-RAFT-RGD T/CM ratio was significantly higher in TS/A-pc than in B16F0 tumours. Conclusion: 99mTc-RAFT-RGD allowed the in vivo imaging of avß3 integrin tumour expression.

Li L, Yazaki PJ, Anderson AL, Crow D, Colcher D, Wu AM, Williams LE, Wong JY, Raubitschek A, Shively JE: Improved biodistribution and radioimmunoimaging with poly(ethylene glycol)-DOTA-conjugated anti-CEA diabody Bioconjug Chem 17(1):68-76 January (2006)

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Abstract
Diabodies are single chain antibody fragments (scFvs) that spontaneously form bivalent dimers of molecular size 50-55000. Radiolabeled diabodies are almost ideal tumor targeting agents due to their high avidity (bivalent) binding to tumor antigens and small size (50-55000) that leads to improved tumor-to-blood ratio compared to intact antibodies (150000). However, due to their high retention and metabolism in the kidney, radioiodine is the current radiolabel of choice for diabodies since radioiodine is rapidly excreted from the kidney once metabolized. We have previously shown that 111In-DOTA-diabody gives higher tumor uptake in nude mouse xenografts than 125I-diabody, but has extremely high kidney retention since its 111In-labeled metabolites are retained by and only slowly excreted from the kidney. When a diabody is conjugated to a bifunctional PEG-3400 derivative followed by reaction with cysteinyl-DOTA, the resulting product has an apparent molecular size of 75000 and a Stokes radius of 35 angstroms on size exclusion chromatography, compared to a Stokes radius of 25 angstroms for intact diabody. When radiolabeled, the conjugate gives high yields of 111In-labeled product, retains high immunoreactivity, and gives improved biodistributions (30-40%ID/g, 12-48 h) compared to 111In-DOTA-diabody (12-13%ID/g, 6-12 h). We show that the improved biodistribution is due to an increase in Stokes radius caused by the linear PEG-3400 since conjugation of diabody with multiple (PEG)12 linkers followed by reaction with cysteinyl-DOTA does not reduce kidney accumulation. We also show that 111In-cysteinyl-DOTA-PEG3400-diabody gives excellent tumor images in the nude mouse xenograft model and that 125I-PEG3400-diabody gives equivalent images to 125I-minibody (molecular size, 80000), but improved tumor-to-liver ratios, suggesting that this imaging agent can be used to image liver metastases.

Crow DM, Williams L, Colcher D, Wong JY, Raubitschek A, Shively JE: Combined radioimmunotherapy and chemotherapy of breast tumors with Y-90-labeled anti-Her2 and anti-CEA antibodies with taxol Bioconjug Chem 16(5):1117-25 August (2005)

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Abstract
Because breast cancer cells often express either Her2/neu or carcinoembryonic antigen (CEA) or both, these tumor markers are good targets for radioimmunotherapy using Y-90-labeled antibodies. We performed studies on nude mice bearing xenografts from MCF7, a cell line that has low Her2 and CEA expression, to more accurately reflect the more usual situation in breast cancer. Although uptake of In-111 anti-CEA into tumors was lower than that for In-111-labeled anti-Her2, radioimmunotherapy (RIT) with Y-90 anti-CEA was equivalent to that of Y-90 anti-Her2. When either Y-90 antibody was combined with a split-dose treatment with Taxol, the antitumor effect was greater than with either agent alone. When Y-90 anti-CEA was combined with a single dose of Taxol, the results were equivalent to the split-dose regimen. RIT plus cold Herceptin had no additional effects on tumor size reduction over RIT alone. When animals were first treated with Y-90 anti-Her2 and imaged 1-2 weeks later with In-111 anti-CEA or anti-Her2, tumor uptake was higher for anti-CEA and improved over tumor uptake with no prior RIT. These results suggest that a split dose of RIT with anti-Her2 antibody followed by anti-CEA antibody would be more effective than a single dose of either. This prediction was partially confirmed in a controlled study comparing single- vs split-dose anti-Her2 RIT followed by either anti-Her2 or anti-CEA RIT. These studies suggest that combined RIT and Taxol therapy are suitable in breast cancers expressing either low amounts of Her2 or CEA, thus expanding the number of eligible patients for combined therapies. They further suggest that split-dose RIT using different combinations of Y-90-labeled antibodies is effective in antitumor therapy.

Gagnadoux F, Pape AL, Lemarié E, Lerondel S, Valo I, Leblond V, Racineux JL, Urban T: Aerosol delivery of chemotherapy in an orthotopic model of lung cancer Eur Respir J. 26(4):657-61 June (2005)

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Abstract
The aim of this study was to evaluate the effect on tumour growth of gemcitabine delivered by aerosol in an orthotopic model of lung carcinoma. Large cell carcinoma (NCI-H460) cells were implanted intrabronchially in 24 male BALB/c nude mice on day (d) 0. Aerosols were delivered once a week from d1 to d29 using an endotracheal sprayer. Altogether, 16 animals received gemcitabine at 8 (n=8) and 12 mg.kg-1 (n=8), and eight received a vehicle aerosol. Animals were sacrificed on d36 for histological examination. All animals in the vehicle group developed a large infiltrating carcinoma. Comparatively, four of 13 (31%) animals treated with gemcitabine had no visible tumour and nine of 13 (69%) had a smaller carcinoma with a mean+/-sem largest tumour diameter of 2.05+/-0.7 versus 5+/-0.3 mm in the vehicle group. Gemcitabine was well tolerated at 8 mg.kg-1. At 12 mg.kg-1, three cases of fatal pulmonary oedema were observed, prompting a dose reduction to 8 mg.kg-1 in the remaining animals. A dose effect was observed, with more marked tumour growth inhibition in the animals treated at 12 mg.kg-1 on d1 and d8. In conclusion, in this study, an animal model of aerosolised chemotherapy in lung cancer was developed and demonstrated inhibition of orthotopic tumour growth by aerosol delivery of gemcitabine.

Gagnadoux F, Le Pape A, Urban T, Montharu J, Vecellio L, Dubus JC, Leblond V, Diot P, Grimbert D, Racineux JL, Lemarié E: Safety of pulmonary administration of gemcitabine in rats J Aerosol Med. 18(2):198-206 July (2005)

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Abstract
The purpose of this research was to evaluate the safety of pulmonary administration of gemcitabine and to determine the maximum tolerated dose by weekly pulmonary administrations in an animal model. Five groups of eight Wistar rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution by endotracheal spray with scintigraphic imaging of lung deposition. In order to document the safety of digestive exposure, five groups of eight rats received gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly sessions were planned, and blood cell counts and histological examinations were performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of deposition. The maximum tolerated dose of gemcitabine by pulmonary administration was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks, there were no chemotherapy-related deaths and no clinical, histological, or hematological signs of toxicity except for a decrease in platelet and red blood cell counts, with no clinical significance. The toxicity of gemcitabine was higher via oral than lung delivery in terms of weight loss and white blood cell toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral administration.

Yazaki PJ, Sherman MA, Shively JE, Ikle D, Williams LE, Wong JY, Colcher D, Wu AM, Raubitschek AA: Humanization of the anti-CEA T84.66 antibody based on crystal structure data Protein Eng Des Sel. 17(5):481-9 May (2004)

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Abstract
Chimeric T84.66 (cT84.66) is a monoclonal antibody (mAb) of high specificity and affinity for the tumor-associated carcinoembryonic antigen (CEA). Radiolabeled cT84.66 has demonstrated utility in the clinic as a reagent for the radioimmunoscintigraphy and radioimmunotherapy of CEA-positive colorectal and breast malignancies. To extend the therapeutic efficacy of T84.66, humanization by complementary determining region (CDR) grafting was employed. CDR grafting is a well-established technique, though often a series of framework back-mutations is required to restore high affinity. Recently, the crystal structure of the T84.66 diabody (scFv dimer) derived from the murine T84.66 mAb was determined, facilitating the humanization process by the availability of crystal structure data for both the graft donor and graft acceptor. A search of the Protein Data Bank revealed close structural similarity (r.m.s.d. of 1.07 A) between the Fv of T84.66 and the Fv of 4D5v8, a humanized anti-p185HER2 antibody marketed as Herceptin (Trastuzumab). This resulted in two humanized versions of the T84.66 M5A and M5B mAbs that differed only in the number of murine residues present in the C-terminal half of CDR-H2. Biochemical analysis and animal biodistribution studies were conducted to evaluate the humanized mAbs. The M5A, M5B and cT84.66 mAbs showed sub-nanomolar affinity for CEA and as radiolabeled mAbs exhibited specific tumor localization in tumor bearing mice. The T84.66 M5A mAb was selected for clinical development due to a slightly higher tumor uptake and a larger content of human residues, and was renamed hT84.66. A limited-scale production and animal imaging study have demonstrated hT84.66's ability to support clinical trials. Planned clinical trials will determine the effective utilization of this structure-based approach in the development of a promising new therapeutic.

Cardiovascular Research

Muzard J, Sarda-Mantel L, Loyau S, Meulemans A, Louedec L, Bantsimba-Malanda C, Hervatin F, Marchal-Somme J, Michel JB, Le Guludec D, Billiald P, Jandrot-Perrus M: Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI PLoS One 4(5):e5585 May (2009)

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Abstract
Background: Fibrosis, which is characterized by the pathological accumulation of collagen, is recognized as an important feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methods for the early diagnosis and follow-up of fibrosis in various disorders. Collagen targeting molecules are therefore of interest for potential in vivo imaging of fibrosis. In this study, we developed a collagen-specific probe using a new approach that takes advantage of the inherent specificity of Glycoprotein VI (GPVI), the main platelet receptor for collagens I and III.
Methodology/Principal Findings: An anti-GPVI antibody that neutralizes collagen-binding was used to screen a bacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin) was synthesized. Solid-phase binding assays and histochemical analysis showed that collagelin specifically bound to collagen (Kd 10-7 M) in vitro, and labelled collagen fibers ex vivo on sections of rat aorta and rat tail. Collagelin is therefore a new specific probe for collagen. The suitability of collagelin as an in vivo probe was tested in a rat model of healed myocardial infarctions (MI). Injecting Tc-99m-labelled collagelin and scintigraphic imaging showed that uptake of the probe occurred in the cardiac area of rats with MI, but not in controls. Post mortem autoradiography and histological analysis of heart sections showed that the labeled areas coincided with fibrosis. Scintigraphic molecular imaging with collagelin provides high resolution, and good contrast between the fibrotic scars and healthy tissues. The capacity of collagelin to image fibrosis in vivo was confirmed in a mouse model of lung fibrosis.
Conclusion/Significance: Collagelin is a new collagen-targeting agent which may be useful for non-invasive detection of fibrosis in a broad spectrum of diseases.

Houard X, Rouzet F, Touat Z, Philippe M, Dominguez M, Fontaine V, Sarda-Mantel L, Meulemans A, Le Guludec D, Meilhac O, Michel JB: Topology of the fibrinolytic system within the mural thrombus of human abdominal aortic aneurysms J Pathol. 212(1):20-8 May (2007)

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Abstract
Development and progression of acquired abdominal aortic aneurysms (AAAs) involve proteolytic activity. In the present study, we investigate the distribution of fibrinolytic system components within mural thrombi of human AAAs. 20 mural thrombi and the remaining AAA walls were dissected. The luminal, intermediate and abluminal thrombus layers, and media and adventitia were separately incubated in cell culture medium. Conditioned media were then analysed for plasminogen activators (PAs), plasminogen activator inhibitor-1 (PAI-1), free-plasmin, plasmin alpha(2)-antiplasmin complexes (PAPs) and D-dimers release. In parallel, PA and PAI-1 mRNA expression analysis was performed by RT-PCR. The study was completed by immunohistochemical localization of these components in AAA, ex vivo functional imaging using (99m)Tc-aprotinin as a ligand and measurement of PAP and D-dimer plasma levels. All fibrinolytic system components were present in each aneurysmal layer. However, the mural thrombus was the main source of active serine-protease release. Interestingly, the luminal layer of the thrombus released greater amounts of PAPs and D-dimers. This paralleled the preferential immunolocalization of plasminogen and PAs, and the (99m)Tc-aprotinin scintigraphic signal observed in the luminal pole of the thrombus. In contrast, mRNA expression analysis showed an exclusive synthesis of tPA and PAI-1 within the wall, whereas uPA mRNA was also expressed within the thrombus. Taken together, these results suggest that the increased plasma concentrations of PAPs and D-dimers found in AAA patients are related to mural thrombus proteolytic activity, thus explaining their known link with AAA progression. Components of the fibrinolytic system could also represent a target for functional imaging of thrombus activities in AAA. Copyright (c) 2007 Pathological Society of Great Britain and Ireland.

Sarda-Mantel L, Coutard M, Rouzet F, Raguin O, Vrigneaud JM, Hervatin F, Martet G, Touat Z, Merlet P, Le Guludec D, Michel JB: 99mTc-annexin-V functional imaging of luminal thrombus activity in abdominal aortic aneurysms Arterioscler Thromb Vasc Biol. 26(9):2153-9 July (2006)

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Abstract
BACKGROUND: The mural thrombus of abdominal aortic aneurysms (AAA) is involved in aneurysm progression via several interdependent biological processes including platelet activation. 99mTc-annexin V (ANX) is a scintigraphic tracer that binds to phosphatidylserine exposed on activated platelets and apoptotic cells. Here, we evaluated the potential of ANX imaging to assess mural thrombus biological activity in an experimental AAA model. The clinical applicability was further tested ex vivo on human samples of excised AAA thrombi. METHODS AND RESULTS: Experimental AAA was created by infusing elastase into infrarenal abdominal aorta in 17 rats, and 6 sham-operated rats were used as controls. Abdominal ANX scintigraphy was performed 2 weeks later followed by quantitative autoradiography and histological studies. Among the 13 rats which developed AAA, 11 displayed intense ANX uptake within AAA by scintigraphy. ANX uptake in the aneurysms on planar and single-photon emission computed tomography (SPECT) imaging was higher than that observed in infrarenal aorta of sham-operated controls (target/background ratio: 5.7+/-0.9 versus 1.33+/-0.21; P<0.005 for SPECT). Aneurysm-to-background activity ratios obtained by scintigraphy correlated with ANX activity in corresponding autoradiograms (R=0.69; P<0.02). This activity was located in the thrombus area where activated platelets and polymorphonuclear leukocytes accumulated. Similar patterns were also found in all of the 7 human AAA thrombi harvested during surgery. CONCLUSIONS: ANX imaging may assess mural thrombus renewal activity linked to permanent flowing blood interface.

Riou LM, Broisat A, Dimastromatteo J, Vanzetto G, Fagret D, Ghezzi C: The in vivo cardiac kinetics of Tc-99m N-NOET are accelerated in obese, hyperlipidemic Zucker rats J Nucl Cardiol. 13(1):75-82 February (2006)

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Abstract
BACKGROUND: Previous studies demonstrated that the intrinsic myocardial washout of bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium(V) (technetium 99m N-NOET) was affected by changes occurring in the intravascular compartment such as variations in circulating lipid levels. We sought to determine whether the myocardial kinetics of Tc-99m N-NOET were affected by hyperlipidemia in a clinically relevant experimental model. METHODS AND RESULTS: Tc-99m N-NOET (50 MBq/kg) and thallium 201 (12 MBq/kg) were injected intravenously into hyperlipidemic fa/fa Zucker rats (n=6) and their lean, normolipidemic littermates (n=8), and dual-isotope in vivo planar imaging was performed for 60 minutes. In vivo image quantification indicated significantly faster cardiac washout of Tc-99m N-NOET in fa/fa animals versus lean animals (time constant, 411+/-64 minutes vs 1094+/-226 minutes, respectively; P<.05), whereas Tl-201 cardiac washout was not affected (356+/-85 minutes vs 337+/-53 minutes, respectively; P=not significant). CONCLUSION: The cardiac kinetics of Tc-99m N-NOET, but not those of Tl-201, were accelerated after intravenous injection of the tracer in fa/fa Zucker rats with circulating lipid levels similar to those encountered clinically in hyperlipidemic patients. The relationship between lipidemia and the rate of Tc-99m N-NOET myocardial washout warrants further clinical investigation.

Gene Therapy

Delépine P, Montier T, Guillaume C, Vaysse L, Le Pape A, Ferec C: Visualization of the transgene distribution according to the administration route allows prediction of the transfection efficacy and validation of the results obtained Gene Ther. 9(11):736-9 June (2002)

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Abstract
Gene transfer to the lung can be achieved via a systemic, that targets the endothelium, or local, that targets the epithelium, delivery route. In the present study, we followed the distribution of a plasmid after transfection using some of our phosphonolipids, which have previously shown their efficiency in transfecting mouse lungs. The plasmid was radiolabeled and varying combinations of plasmid/phosphonolipid were administered by intravenous injection, or by endotracheal spray. The distribution of radioactive labeling was observed over a time course using a gamma-camera. These images were then correlated with the results for luciferase expression levels in the lungs. In each case, lungs were well targeted. However, whereas an intravenous injection reaches all of the lung immediately, progressive diffusion occurs when the plasmid/phosphonolipid is administered via an aerosol. Elimination of the radioactivity associated with plasmid occurs via the urinary tract after intravenous injections, and via the feces using the aerosol delivery approach. The radioactivity detected in the lungs correlated strongly with transgene expression. Thus, such an imaging technique is a powerful strategy to predict the formulation that will generate the best transfection efficiency. This study reveals that scintigraphic imaging permits both validation of the administration method and the results obtained for each animal, thereby reducing the statistical variability of in vivo experiments.

Delépine P, Guillaume C, Montier T, Clément JC, Yaouanc JJ, Des Abbayes H, Berthou F, Le Pape A, Férec C: Biodistribution study of phosphonolipids: a class of non-viral vectors efficient in mice lung-directed gene transfer J Gene Med. 5(7):600-8 January (2003)

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Abstract
BACKGROUND: A multitude of cationic lipids have been synthesized since they were first proposed for use in gene therapy. Cationic lipids are able to efficiently transfect cells both in vitro and in vivo. Whereas most research groups have focused their investigations on the toxicity of these molecules, and on the location of expression of the DNA transferred by these vectors, little has been done to determine their biodistribution and elimination pathways. Our group has developed a family of cationic lipids termed phosphonolipids. Following a large in vitro screening experiment, we have selected several molecules for in vivo testing, with some of these phosphonolipids forming lipoplexes efficient in transfecting mouse lungs. It was thus of interest to study their fate after intravenous injection. METHODS: The respective biodistributions of both the GLB43 phosphonolipid and plasmid DNA were investigated and compared with DNA expression sites. Using the optimal conditions determined for phosphonolipids, we followed the gene transfer agent and plasmid DNA distributions versus time by radiolabeling them with (14)C and (32)P, respectively. Otherwise, we performed imaging by radiolabeling plasmid DNA with (99m)Tc. RESULTS: The lipoplexes appear to be directly located in the lung after administration. Secondly, the plasmid is released mainly into the lungs and the phosphonolipid vector is rapidly degraded. The hydrophilic moiety of the phosphonolipid is eliminated in the urine, as is the free plasmid. CONCLUSIONS: This study reveals that there are slight differences in the observed results depending on the technique used to label the DNA; secondly, results show that the residence time of phosphonolipids in the mouse body is related to the DNA binding time.

Molecular Imaging

Miot-Noirault E, Vidal A, Auzeloux P, Madelmont JC, Maublant J, Moins N: First In Vivo SPECT Imaging of Mouse Femorotibial Cartilage Using 99mTc-NTP 15-5 Mol Imaging. 7(6):263-71 November (2008)

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Abstract
This study aimed to report the first single-photon emission computed tomographic (SPECT) imaging of articular cartilage in mice using 99mTc-NTP 15-5 radiotracer. Mice intravenously injected with 99mTc-NTP 15-5 were submitted to (1) dynamic planar imaging, (2) static planar imaging, (3) 1 mm pinhole SPECT acquisition, and (4) dissection. Tomographic reconstruction of SPECT data was performed with a three-dimensional ordered subset expectation maximization algorithm, and slices were reconstructed in three axes. 99mTc-NTP 15-5 rapidly accumulated in the joint, with a peak of radioactivity being reached from 5 minutes postinjection and maintained for at least 90 minutes. Given that bone and muscle did not show any accumulation of the tracer, highly contrasted joint imaging was obtained from 15 minutes postinjection. When 1 mm pinhole SPECT acquisition was focused on the knee, the medial and lateral compartments of both the femoral condyle and tibial plateau were highly delineated, allowing a separate quantitation of tracer accumulation within each component of the femorotibial joint. A good correlation was found between tracer uptake determined by region of interest analysis of both planar and SPECT scans and dissection. This new approach to imaging of cartilage in mice provides joint functionality assessment in vivo, giving a unique opportunity to achieve a greater understanding of cartilage physiology in health and disease.

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