Errors associated with VOI activity measurements are large and are strongly dependent on the number and definition of each ROI used in the determination of the VOI. (t1/2.eff and t1/2.biol) have been calculated.(0.13 MB TIF) pone.0008859.s005.tif (122K) GUID:?F347598A-C895-44E0-B16E-A14E0E8D32D7 Figure Baicalein S5: Plot of the total normalized, average number of coincident counts recorded via immunoPET imaging of MDA-MB-468 tumor-bearing mice (n?=?4) versus time/h. Exponential decay regression analysis has been used to calculate the effective lifetime (eff/h) and decay constant (eff/h?1) from which the estimated observed and biological half-lives (t1/2.eff and t1/2.biol) have be calculated.(0.13 MB TIF) pone.0008859.s006.tif (124K) GUID:?36DCD575-7201-49DB-AB6A-8BC0DDA7D107 Table S1: Biodistribution data of 89Zr-DFO-trastuzumab versus time/h, administered by i.v. tail-vein injection to female, athymic nu/nu mice bearing s.c. BT-474 tumors (90C150 mm3).a (0.11 MB DOC) pone.0008859.s007.doc (103K) GUID:?71B158C5-B9C5-43DF-AD3F-8BF19078E8D4 Table S2: A comparison of the difference between mean BT-474 tumor uptake values observed in the biodistribution studies in control (vehicle-treated) and PU-H71 treated mice.(0.04 MB DOC) pone.0008859.s008.doc (38K) GUID:?A0FD07F7-7929-47A2-9FB1-8119BCDB51E5 Table S3: Tumor-to-muscle (T/M) ratios have been calculated from volume-of-interest (VOI) analysis of immunoPET images recorded in dual tumor-bearing (BT-474 and MDA-MB-468) female, athymic nu/nu mice between 1C120 h post-i.v. administration of 89Zr-DFO-trastuzumab. The data presented are ratios of mean and maximum (%ID/g) values. Errors associated Rabbit Polyclonal to HSD11B1 with VOI activity measurements are large and are strongly dependent on the number and definition of each ROI used in the determination of the VOI. As a consequence of the large errors associated with VOI analysis, and the further exaggeration that ensues from the calculation of ratios, errors associated with the calculated ratios are large, difficult to define and have been omitted to avoid misrepresentation of the data.(0.05 MB DOC) pone.0008859.s009.doc (49K) GUID:?A6C2A202-AFB5-4785-B8B7-38E9637D3CA1 Table S4: Summary of the calculated effective and biological half-lives(0.04 MB DOC) pone.0008859.s010.doc (37K) GUID:?6FEF599F-B5FD-4FF4-B23A-150EA5FF460B Abstract Background The positron-emitting radionuclide 89Zr (expression levels in response to therapeutic doses of PU-H71 Baicalein (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted. Methodology/Principal Findings Trastuzumab was functionalized with desferrioxamine B (DFO) and radiolabeled with [89Zr]Zr-oxalate at room temperature using modified literature methods. ImmunoPET Baicalein and biodistribution experiments in female, athymic mice bearing sub-cutaneous BT-474 (HER2/positive) and/or MDA-MB-468 (HER2/negative) tumor xenografts were conducted. The change in 89Zr-DFO-trastuzumab tissue uptake in response to high- and low-specific-activity formulations and co-administration of PU-H71 was evaluated by biodistribution studies, Western blot analysis and immunoPET. 89Zr-DFO-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity 104.32.1 MBq/mg (2.820.05 mCi/mg of mAb). assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.870.07. biodistribution experiments revealed high specific BT-474 uptake after 24, 48 and 72 h (64.6813.06%ID/g; 71.7110.35%ID/g and 85.1811.10%ID/g, respectively) with retention of activity for over 120 h. Pre-treatment with PU-H71 was followed by biodistribution studies and immunoPET of 89Zr-DFO-trastuzumab. Expression levels of HER2/were modulated during the first 24 and 48 h post-administration (29.754.43%ID/g and 41.423.64%ID/g, respectively). By 72 h radiotracer uptake (73.6412.17%ID/g) and Western blot analysis demonstrated that HER2/expression recovered to baseline levels. Conclusions/Significance The results indicate that 89Zr-DFO-trastuzumab provides quantitative and highly-specific delineation of HER2/positive tumors, and has potential to be used to measure the Baicalein efficacy of long-term treatment with Hsp90 inhibitors, like PU-H71, which display extended pharmacodynamic profiles. Introduction In the era of molecular medicine, antibody-based agents offer unparalleled potential as platforms for the development of target-specific therapies.[1] Immunoconjugates are monoclonal antibodies (mAbs) or antibody fragments functionalized with cytotoxic and/or diagnostic payloads. Increasing availability of longer-lived positron-emitting radionuclides such as 64Cu, 86Y, 89Zr and 124I, and advances in chelation chemistry, have renewed interest in the use of positron emission tomography with radioimmunoconjugates (immunoPET) as a tool for providing real-time, quantitative information on physiological response to treatment.[2]C[5] Proteins associated with the human epidermal growth-factor receptor kinase (ERBB or HER) signaling network have proved.
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