Curr Top Med Chem. An improved synthesis of substituted [ 11 C]toluenes via Suzuki coupling with [ 11 C]methyl iodide. J Labelled Comp Radiopharm. Synthesis, in vitro and in vivo evaluation of fluorine labelled FE-GW as a PET tracer for type 2 cannabinoid receptor imaging. Bioorg Med Chem. A PET brain reporter gene system based on type 2 cannabinoid receptors.
Chem Commun Camb ; 49 —6. Synthesis of the Cyanine 7 labeled neutrophil-specific agents for noninvasive near infrared fluorescence imaging. Bioorg Med Chem Lett. Bioconjugate Chem. Synthesis of novel neutrophil-specific imaging agents for positron emission tomography PET imaging. Hum Antibodies. Hawkey CJ. COX-2 inhibitors. Katori M, Majima M. Cyclooxygenase its rich diversity of roles and possible application of its selective inhibitors.
Inflamm Res. Minghetti L. Cyclooxygenase-2 COX-2 in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. Evaluation of [ 11 C]rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation. In vivo expression of cyclooxygenase-1 in activated microglia and macrophages during neuroinflammation visualized by PET with 11 C-ketoprofen methyl ester. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study. Synthesis and preliminary in vitro biological evaluation of new carbonlabeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer.
Eur J Med Chem. Synthesis and evaluation in vitro and in vivo of a 11 C-labeled cyclooxygenase-2 COX-2 inhibitor. Cancer Prev Res Phila ; 4 — Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. Measurement of MMP activity in synovial fluid in cases of osteoarthritis and acute inflammatory conditions of the knee joints using a fluorogenic peptide probe-immobilized diagnostic kit. Optical imaging of cancer-related proteases using near-infrared fluorescence matrix metalloproteinase-sensitive and cathepsin B-sensitive probes.
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Salmi M, Jalkanen S. VAP an adhesin and an enzyme. Trends Immunol. Clin Physiol Funct Imaging. Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer. Synthesis, 68 Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein a potential PET imaging agent for diagnosing osteomyelitis. In Vivo. Ley K, Huo Y. VCAM-1 is critical in atherosclerosis. J Clin Invest. Tsan MF. Mechanism of gallium accumulation in inflammatory lesions. Ross R. Atherosclerosis--an inflammatory disease.
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We also recommend that a new baseline PET be obtained before initiation of a new therapeutic regimen. Should a biopsy be necessary, PET may also help guide the biopsy to the relevant part of a tumor mass. Early identification of non-responders is certainly a major goal. No one wants to expose a patient to any treatment if he or she is not going to derive significant benefit from it.
I think that imaging has a role to play soon after initiation of drug therapy to allow for an earlier change to alternative therapy and to avoid unnecessary toxicity in patients who are not responding. I also believe that PET imaging has propelled science forward — particularly in patients with GIST — by giving us a simple, noninvasive, and rapid way to demonstrate biologic effects on the tumor as early as hours after a single dose of the drug, as we have shown with imatinib.
These profound metabolic changes within the tumor are consistent with response to therapy and precede significant changes in tumor size by weeks and months. If we can see what works and what does not early on, we can direct our energies and research dollars accordingly. The use of functional imaging with PET has already shortened the length of several clinical trials, with the result that new drugs became available to the public sooner than would otherwise have been the case, and development costs were re duced.
We demonstrated this with sunitinib and helped bring the drug to the market six months ahead of schedule based on feedback from the company. I also anticipate that imaging, and in particular functional imaging with PET, will play a major role in the future in the delivery of personalized medicine. I think that imaging can lead to significant cost savings by helping identify the right patient for the right drug.
So the facilitation of clinical trials, drug development, and personalized medicine through the use of imaging would be other major goals. Metabolic changes tend to precede structural changes within the tumor and are predictive of both clinical and subsequent radiologic responses. Qualitative and quantitative imaging methods can be used to assess metabolic response to therapy.
A complete metabolic response by either qualitative or quantitative evaluation is highly predictive of good outcome. Conversely, persistent metabolic activity suggests residual tumor, and recurrent tumor activity in an area that had previously shown response may be indicative of secondary resistance. Several quantitative and semi-quantitative methods can be used to assess metabolic response, but these vary in complexity and reproducibility and are mainly used in the context of clinical trials.
Because the metabolic response to drug treatment precedes the anatomic response, reductions in tumor activity may be seen in as little as 24 hours — long before physical shrinkage is visible on CT or MRI. Thus, PET is a really efficient tool for determining how well a drug is working in a particular patient. If the CT scan shows stability or shrinkage, that is probably all the information the oncologist needs to know to assess if the drug is working, and if you should stay on that drug.
Where PET is really valuable is in resolving discrepancies between the CT scan and clinical findings: for example, the CT may show an increase in tumor growth but other clinical information suggests that the patient is actually doing well. A negative PET scan will confirm that this is the case. Conversely, tumors may look stable in size on CT but show small nodular development within the wall of the mass. PET can also be very helpful in guiding the biopsy to these sites of active tumor metabolism and possible secondary resistance. FDG-PET is an ideal imaging tool in GIST for staging the disease, assessing therapeutic response, evaluating primary and secondary resistance, and resolving discrepant results between CT and the clinical findings.