Biomarker Development - Research Support

Current Support

Thrasos, Inc
Radiolabeling and Pharmacokinetics of Protein Agents.
The goal is to investigate the radiology of the specified agents, their stability in-vitro and distribution in animal models.
Genzyme, Inc.
Radiolabeling of Candidate Drug Leads for Pharmacokinetic and Biodistribution by Imaging.
Biogen Idec
Radiolabeling of Candidate Drug Leads for Pharmacokinetic and Biodistribution by Imaging.
Tag-72 Targeted Imaging for Cancer Detection.
The goal of this research is to develop a 99mTc-peptide agent for the diagnosis of ovarian cancer through scintigraphic imaging. The agent developed in these studies could be of great benefit in the diagnosis of ovarian cancer, not only the primary site of disease, but possibly metastases as well.
Labeled Bacteriophage for Infection-Specific Imaging.
The overall objective of this proposed investigation is to establish whether radiolabeled bacteriophages may be useful as bacteria-specific infection imaging agents. The specific goals are to determine the stability of 99mTc on phage when radiolabeled via MAG3 to determine the fate of the radiolabeled phage infecting both live and heat killed bacteria, and to help establish whether radiolabeled phage may be used to distinguish by imaging, infection from inflammation.
Oligomers for Infection Detection.
The objective of this investigation is to establish whether radiolabeled oligomers may be useful as bacterial-specific infection imaging agents, and thus be used to distinguish through imaging, infection from inflammation. We expect to demonstrate that the accumulation of species-specific 99mTc-labeled bacterial oligomers will localize in our mouse model of infection/inflammation in a manner consistent with localization specific to bacterial infections and that the extent of localization will exceed that displayed by UBI, a documented bacteria-specific imaging agent and 99mTc-Infecton.
Diagnostic SPECT & PET fungal Infection Imaging Using Fungal Specific rRNA Probes.
Our overall objective is to investigate whether fungal specific oligomers, specific to segments of the ribosomal RNA, once radiolabeled, can be used in vivo for the diagnostic detection of fungal infection, in particular Aspergillus fumigatus, through diagnostic imaging. The studies will first investigate in vitro the targeting of labeled oligomers to ribosomal RNA of 5 Aspergillus species and 5 Candida species, and secondly, investigate in mouse models the targeting of labeled oligomers to Aspergillus species and Candida species specific probes.
Pretargeting Mouse Tumor with Anti-Psma Antibody-Morf.
Despite several decades of effort, conventional radioimmunodetection of prostate cancer is still providing marginal results because of the slow pharmacokinetics and localization in normal tissues. ProstaScint is the only FDA approved prostate cancer imaging agent currently available. In addition to the intrinsic problems with conventional radioimmunodetection, it targets an intracellular epitope difficult to be accessed. As such, alternative methods for the sensitive and selective detection of prostate cancers are needed. One of the most attractive alternative approaches to imaging prostate cancer involves pretargeting. On other tumor types, preclinical studies of pretargeting have clearly demonstrated efficacy and early clinical trials are providing encouraging results. This proposal will use an antibody with high affinity against an extracellular and conformational epitope of PSMA, the 3C6, along with a pretargeting strategy in a mouse prostate cancer model. The non-radioactive 3C6 conjugated with a morpholino oligomer (MORF) will be injected and followed at a later time with a low molecular weight radiolabeled complementary morpholino oligomer (cMORF). The antibody 3C6 shows extremely high affinity for the extracellular conformational epitope of PSMA. The radiolabeled cMORF can hybridize with the MORF, clear very rapidly from the normal tissues, and excrete exclusively through the kidneys. An image of diagnostic quality should be obtained very rapidly in contrast to conventional imaging with radiolabeled ProstaScint. This proposed study seeks to show that pretargeting with MORFs along with an extracellular antibody may image prostate cancer in a mouse model more effectively than ProstaScint (as a gold standard). Thus, we intend to optimize conditions of dosage and timing for pretargeted localization of 99mTc-cMORF in mice with prostate xenografts having previously received MORF-conjugated prostate specific antibodies. Application of pretargeting strategy along with an extracellular antibody will translate into a more sensitive imaging method than the conventional ProstaScint. Successful pretargeting with antibody and MORF will demonstrate the advantages over anatomical imaging methods such as Ultrasound, CT, and MRI, so that a more efficient means for early detection of prostate cancer might be possible. Based on our experiences in this pretargeting strategy, we are confident that these investigations on the pretargeting imaging of prostate cancer models with MORFs will be successful.
Improved Tumor Rediotherapy by Morf Pretargeting

Other Support

Worcester Foundation for Biomedical Research
Identification of Biomarkers of Vulnerable Atherosclerotic Plaques.

PK through imaging of 177Lu-bombesin.