Cjgaddy, I scanned through the article. It looks to me that the researchers have refined the use of the diagnostic version of Bavi to achieve better results. I have no way of knowing just how good these results are. I hope some company with an interest in this area finds the research tempting to partner.
Thanks for your post. Much more interesting than the usual crapola about Fargo.
SNMMI Annual Mtg (June11-14-2012): 2 Bavi Imaging abstracts presented
The Society of Nuclear Medicine & Molecular Imaging (SNMMI) finished their Annual Meeting June 14th 2014. There are 2 abstracts pertaining to bavituximab. They are pretty technical, but do show that work is continuing on Imaging. In the 1st one, the radioisotope Iodine-131 is linked to bavi (I-131 is the radioisotope used in Cotara). The abstract uses the phrase "radioimmunotheranostic agents", which combines the use of the radioisotope with the antibody as a dual therapeutic & diagnostic agent. LNCaP is a prostate cancer cell line.
= = = = = = = = = = = = = = Abstract #1068 (SNMMI June 11-14 2014) ”Immuno-SPECT of a potential radioimmunotheranostic agent: 131I-labeled bavituximab" Guiyang Hao, Gedaa Hassan, Orhan Oz, Xiankai Sun Univ. of Texas SW Medical Center, Dallas http://jnumedmtg.snmjournals.org/cgi/content/meeting_abstract/55/1_MeetingAbstracts/1068 OBJECTIVES: I-131 is commonly used in human cancer radioimmunotherapy. However, the diagnostic value of 131I-enabled radioimmunotherapeutic agents is largely neglected due to the suboptimal 364 KeV energy. As imaging technologies evolve, high-energy apertures have become more readily available for SPECT scanners. Here we report our preliminary evaluation of the imaging potential of an 131I-labeled antibody using high-energy apertures on a BioScan NanoSPECT/CT system. The antibody, Bavituximab (Bavi), binds to a complex of B2 glycoprotein 1 and phosphatidylserine and thus triggers antitumor effects. METHODS: Bavituximab was labeled with 131I using the IODO-GEN method. A phantom study and the SPECT/CT scans with 131I-Bavi in LNCaP tumor bearing mice were performed using both High Energy Gamma (I-131) and High Resolution aperture plates. All images were acquired on a BioScan NanoSPECT/CT Plus system equipped with 4 detectors. RESULTS: The 131I-Bavi was obtained at 0.92 MBq/ug and 28 µg injected into each mouse. Scans obtained using the High Resolution apertures showed poor tumor or organ contrast with noisy background due to aperture penetration by the high energy gamma photons. In tumor bearing mice, the LNCaP tumor, liver, and thyroid were clearly visualized at 24, 48, and 72 h p.i. when the High Energy Gamma apertures were used. In addition, an increasing tumor contrast was observed as the 131I-Bavi was gradually cleared from the liver and other non-target organs. CONCLUSIONS: We successfully demonstrated the feasibility of using high-energy apertures to perform immunoSPECT of 131I-Bavi in a mouse tumor model. It is promising that 131I-labeled antibodies can be developed as radioimmunotheranostic agents. Research Support: The purchase of the BioScan NanoSPECT/CT Plus System was partially supported by an NIH NCRR grant (1S10RR029674-01).
--------------------------------------------------------------------------------- Abstract #1185 (SNMMI June 11-14 2014) ”A click-chemistry based strategy for labeling an anti-phosphatidylserine (PS) antibody with copper-64 via a cross-bridged tetraazamacrocyclic chelator scaffold” Amit Kumar, Guiyang Hao, Li Liu, Xiankai Sun Radiology, Univ. of Texas SW Medical Center, Dallas http://jnumedmtg.snmjournals.org/cgi/content/meeting_abstract/55/1_MeetingAbstracts/1185 OBJECTIVES: Cross-bridged tetraazamacrocyclic chelator (CBTE2A) scaffold forms a kinetically inert copper complex with high in vivo stability, and is regarded as one of the "gold standard’’. Unfortunately, due harsh labeling conditions it is not underutilized for antibody labeling. In this work we demonstrate a unique method for antibody labeling under ambient conditions utilizing CBTE2A scaffold. The method involves prelabeling CBTE2A based scaffold (CBTE1A) with 64Cu and its subsequent reaction with antibody via tertrazine-norbornene mediated click reaction. We demonstrate the effectiveness of this technique by labeling and imaging bavituximab, a chimeric monoclonal antibody designed for the treatment of cancers, with 64Cu. METHODS: Norbornene moiety was attached to the free acid group of the tert butyl protected CBTE1A scaffold via carbodiimide chemistry. The compound was then deprotected and labeled with 64Cu in ammonium acetate buffer. Tetrazine moiety was attached to bavituximab via carbodiimide chemistry and the mixture purified by FPLC. Copper-64 labeled CBTE1A was subsequently mixed with tetrazine modified bavituximab in phosphate buffer and the mixture analyzed with radio FPLC. The resultant mixture was purified and in vivo imaging was performed on LNCaP tumor bearing mice. RESULTS: The 64Cu-labeled CBTE1A was obtained in 90% radio labeling yield and greater than 99% purity. The radio FPLC analysis of the reaction mixture showed a strong radio peak for bavituximab. In vivo imaging showed uptake and retention of labeled bavituximab at 48 h post injection. CONCLUSIONS: We have successfully demonstrated a method to radiolabel antibodies under ambient condition using CBTE2A based scaffold. The in vivo results suggest the antibody remains intact throughout the chemical modification. Research Support: This work was partially supported by the Dr. Jack Krohmer Professorship Funds.
= = = = = = = = = =SUMMARY of Bavi-Imaging Work: By Phosphatidylserine 6-15-14 iHub #180088 Those are some new names I haven't seen on the UTSW-MC bavi team. It is amazing the amount and value of work that UTSW-MC has done on PPHM and patients’ behalf. And in particular, Imaging. Here's a list of Bavi-related imaging work - mostly PGN635: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=103316918 11/12/2011 UC Irvine and Peregrine Abstract B116: Imaging of primary tumor and metastases in mice using near-infrared fluorescent-labeled phosphatidylserine-targeting antibodies. http://mct.aacrjournals.org/cgi/content/meeting_abstract/10/11_MeetingAbstracts/B116
11/26/2013 UT Southwestern Medical Center Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model http://www.mdpi.com/1420-3049/18/12/14613
= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = IMAGING APPLICATIONS Of PS-TARGETING MABS: 6-2014: Two Bavi-Imaging abstracts by UTSW at Nuclear Med+Molecular Imaging Annual Mtg http://tinyurl.com/kemdu2d 11-26-13: PGN635 (Fhu-Bavi) Imaging article in Molecules2013 by UTSW’s Liang Zhang & Dawen Zhao http://tinyurl.com/mxzodta ; 10-31-12, New PS-Targeting Preclin. Data - Mabs Stimulate Cancer-Fighting Immune Responses & Specifically Target Tumors http://tinyurl.com/cw9odb8 …10-25-12 SITC Poster on Bavi's MOA, and 10-10-12 NMBA article on "ImmunoPET Imaging of PS" using 89Zr-PGN635 (see Genentech below) 10-12-12: Genentech studying Imaging using PGN635(Fhu-Bavi) for the potential "detection of tumor response to therapy". http://tinyurl.com/8wvem9y …Nuclear Medicine & Biology, Genentech's Jan Marik, "ImmunoPET Imaging of PS in Pro-Apoptotic Therapy Treated Tumor Models" 4-3-12: Peregrine Launches PS-Targeting Clinical Imaging Program (AACR'12 #2452) http://tinyurl.com/7p7jovt & http://tinyurl.com/7yrwqm7 …PPHM "recently filed an IND" with FDA for an Imaging trial using 124I-PGN650, ~12pts. ...6-28-12: Trial added to trials.gov: http://clinicaltrials.gov/ct2/show/NCT01632696 - see CANCER TRIALS ABOVE for more details. 12-2011: Thorpe Article on FH-Bavi/Optical-Imaging in Translational Oncology http://tinyurl.com/7vcnbz2 11-14-11: Dr. Bruce Freimark presents PS IMAGING poster at AACR-NCI-EORTC Conf./SanFran http://tinyurl.com/89hpydn 9-12-11: Drs. Thorpe & Freimark present PS IMAGING posters at World Imaging Congress/S.Diego http://tinyurl.com/3uv5rgr 9-9-11: PS IMAGING potential discussed in Qtly. Conf. Call: http://tinyurl.com/3q7hzjh 4-2011/Neoplasia: Dr. Thorpe 9-pg. article on Exposed-PE/Imaging http://tinyurl.com/5uoy6fh …Dr. Thorpe: "PE also has potential as a marker for Imaging human malignancies." 4-6-11/AACR'11: Tumor Imaging Applications of PS-Targeting Antibodies http://tinyurl.com/68p9zs4 …Steve King: "Molecular imaging is a growing field and represents an entirely new development opportunity for our first-in-class PS-targeting antibody platform… our antibodies labeled with imaging tracers hold potential for illustrating exposed PS in a clinical oncology setting, imaging PS as a companion diagnostic with bavituximab therapy, as well as ultimately assessing patient response to a range of cancer therapies." 3-14-11: Dr. Thorpe discusses PS IMAGING in Conf. Call: http://tinyurl.com/4p4hqr5 …Dr. Thorpe: "The quality of the images is quite extraordinary. The antibody homes to tumor blood vessels beautifully in all tumors that we've seen with really very, very little of a staining seen in other tissues, and that's just what you'd like to see in a diagnostic - we are looking at that very seriously. And also, that binding is correlated to response, both with radiotherapy & chemotherapy. So again, we have the possibility of making a diagnostic that would be predictive of response. We are evaluating that possibility at this time... Duramycin binds PE; binding PE expands our coverage of our broad aminophospholipid-targeting platform, so it really dovetails very beautifully with the existing antibody portfolios. It's expanding our desire to explore different phospholipids as potential targets for therapy & diagnosis… PE is phosphatidylethanolamine and it is the brother of PS. So where PE goes, so does PS and vice versa. So the 2 lipids co-segregate normally on the inside surface of the plasma membrane, but in activated cells or apoptotic cells or stress cells, both lipids flip, and both are potential targets for therapeutics or diagnostics… Duramycin is a little peptide, that's a small molecule and has quite different qualities from an antibody in terms of penetrants. So we're intrigued to see how it plays out, too." 6-24-09 U.S. Patent #7,550,141 granted: Anti-PS for Tumor Imaging: http://tinyurl.com/ln9ub8 3-3-08: Thorpe/Mason C.C.R. (AACR) article on Arsenic-labeled Bavi for Imaging Tumors: http://tinyurl.com/32jbfl …3-5-08 Chemistry World followup article on CCR Bavi+Arsenic/IMAGING: http://tinyurl.com/4m4lbse 2006/SMI: Thorpe/Mason, "Optical Imaging of Exposed PS in Tumors" http://tinyurl.com/42nh7d9 …"We believe optical imaging with Bavituximab holds great promise for assessing PS expression, and therapeutic activity in vivo and optimizing treatment protocols."
5-25-16/OncoTarget article, “PS-Targeted Liposome For Enhanced Glioma-Selective Imaging” - Wake Forest's Dawen Zhao & UTSW's Liang Zhang...
5-25-16/OncoTarget(Imaging): “Phosphatidylserine-Targeted [PGN635=FullyHuman Bavi] Liposome For Enhanced Glioma-Selective Imaging” OncoTarget Journal #9584 - Rec.2-14-16, Acc.4-28-16, Pub.5-25-16 Liang Zhang 1, Amyn A. Habib 2, Dawen Zhao(Wake Forest Univ.) 3,4 1 Dept of Radiology, UTSW-MC/Dallas 2 Dept of Neurology & Neurotherapeutics, UTSW-MC/Dallas 3 Dept of Biomedical Engineering, Wake Forest School of Medicine, Winston Salem, NC 4 Dept of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC FULL ARTICLE: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=9584&path[]=30014 ABSTRACT: Phosphatidylserine (PS), which is normally intracellular, becomes exposed on the outer surface of viable endothelial cells (ECs) of tumor vasculature. Utilizing a PS-targeting antibody, we have recently established a PS-targeted liposomal (PS-L) nanoplatform that has demonstrated to be highly tumor-selective. Because of the vascular lumen-exposed PS that is immediately accessible without a need to penetrate the intact blood brain barrier (BBB), we hypothesize that the systemically administered PS-L binds specifically to tumor vascular ECs, becomes subsequently internalized into the cells and then enables its cargos to be efficiently delivered to glioma parenchyma. To test this, we exploited the dual MRI/optical imaging contrast agents-loaded PS-L and injected it intravenously into mice bearing intracranial U87 glioma. At 24h, both in vivo optical imaging and MRI depicted enhanced tumor contrast, distinct from the surrounding normal brain. Intriguingly, longitudinal MRI revealed temporal and spatial intratumoral distribution of the PS-L by following MRI contrast changes, which appeared punctate in tumor periphery at an earlier time point (4h), but became clustering and disseminated throughout the tumor at 24h post injection. Importantly, glioma-targeting specificity of the PS-L was antigen specific, since a control probe of irrelevant specificity showed minimal accumulation in the glioma. Together, these results indicate that the PS-L nanoplatform enables the enhanced, glioma-targeted delivery of imaging contrast agents by crossing the tumor BBB efficiently, which may also serve as a useful nanoplatform for anti-glioma drugs. CONCLUSIONS: Given the fact that many GBM blood vessels remain impermeable, the discovery and development of a drug delivery system that enables penetration specifically across the tumor BBB will be critical for effective glioma-targeted diagnosis and treatment. In the present study, we demonstrate that the PS-targeted liposomal (PS-L) nanoplatform allows sufficient delivery of the dual imaging contrast agents across the tumor BBB to the glioma parenchyma, which was visualized by in vivo MRI and optical imaging. The temporal and spatial changes in intratumoral MRI contrast may correlate well with the initial binding of the PS-L to tumor vascular ECs and disseminating across the tumor tissues at the later stage. The study thus provides proof of principle for the further development of glioma-targeted nanodelivery of therapeutic agents or theranostic agents for both glioma imaging and treatment. ACKNOWLEDGMENTS: We would like to pay tribute to the late Dr. Philip Thorpe for his pioneered research on phosphatidylserine and development of a series of PS-targeting antibodies. We thank Peregrine Pharmaceuticals Inc., Tustin CA, for the provision of PGN635[PGN635=FullyHuman Bavi] antibody. GRANT SUPPORT: GBM research has been supported in part by NIH R01 CA194578 (DZ) and a grant from the Dept. of Veteran’s Affairs (to AH). Imaging was conducted by NIH P41-RR02584, and DOE grant DE-FG02-05CH11280. Dr. Dawen Zhao: http://www.wakehealth.edu/News-Releases/2015/Zhao_Named_Wells_Fargo_Faculty_Scholar.htm
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