“…The image also shows activity accumulation in organs such as kidney,l iver,b ladder,s pleen and intestines. According to our previous work, [60] this accumulationp attern can be expected, as the metabolism of proteins with molecular weights imilar to aF ab fragment (~55 kDa) is dominated by kidney and liver.T he calculated tumor-to-contralateral muscle ratio of 12 is notably high for as ystemically applied Fab fragment, as Fabs undergo rapid degradation processes and are therefore much more short-lived in the blood than full-length antibodies. [10][11][12] This encourages further studies regarding the in vivo behavior of this 64 Cu-labelled compound for diagnostic imaging of CA XII expressing tumors.…”
Section: Measurementmethodsmentioning
confidence: 62%
“…The cobalt isotopes 55 Co, 57 Co and 61 Co were identifiedw ith contentso f0 .03 AE 0.10, 0.004 AE 0.014 and 1.4 AE 3.4 At %, respectively.T he amount of 64 Cu was determined to be 98.5 AE 3.4 At %. Radionuclides with short half-lives, such as [60][61][62] Cu, were not detected in the examined sample. This supports the implementation of a1 2h time intervalb etweenE OB and EOP for eliminationo fa ny short-lived isotopes.…”
Section: Characterizationmentioning
confidence: 87%
“…This enzyme is expressed on various aggressively growing cancer cells, such as renal carcinoma, breast cancer, ovarian tumors, and gliomas . The 6A10 Fab has already been radiolabelled with 177 Lu and investigated for potential use as a radiotherapy agent against glioma recurrence . Further applications as a diagnostic tracer, radiolabelled with the PET nuclide 64 Cu, is now considered to extend the use of this biomolecule for tumor imaging.…”
Section: Introductionmentioning
confidence: 99%
“…[59] The 6A10 Fab has already been radiolabelledw ith 177 Lu and investigated for potentialu se as a radiotherapy agent against glioma recurrence. [60] Further applications as ad iagnostic tracer,r adiolabelled with the PET nuclide 64 Cu, is now considered to extendt he use of this biomolecule for tumor imaging.…”
Cu is a cyclotron-produced radionuclide which offers, thanks to its characteristic decay scheme, the possibility of combining positron emission tomography (PET) investigations with radiotherapy. We evaluated the Alceo system from Comecer SpA to automatically produce Cu for radiolabelling purposes. We established a Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody Fab fragment was successfully radiolabelled with the produced Cu, and proof-of-principle small-animal PET experiments on mice bearing glioma xenografts were performed. We obtained a high tumor-to-contralateral muscle ratio, which encourages further in vivo investigations of the radioconjugate regarding a possible application in diagnostic tumor imaging.
“…The image also shows activity accumulation in organs such as kidney,l iver,b ladder,s pleen and intestines. According to our previous work, [60] this accumulationp attern can be expected, as the metabolism of proteins with molecular weights imilar to aF ab fragment (~55 kDa) is dominated by kidney and liver.T he calculated tumor-to-contralateral muscle ratio of 12 is notably high for as ystemically applied Fab fragment, as Fabs undergo rapid degradation processes and are therefore much more short-lived in the blood than full-length antibodies. [10][11][12] This encourages further studies regarding the in vivo behavior of this 64 Cu-labelled compound for diagnostic imaging of CA XII expressing tumors.…”
Section: Measurementmethodsmentioning
confidence: 62%
“…The cobalt isotopes 55 Co, 57 Co and 61 Co were identifiedw ith contentso f0 .03 AE 0.10, 0.004 AE 0.014 and 1.4 AE 3.4 At %, respectively.T he amount of 64 Cu was determined to be 98.5 AE 3.4 At %. Radionuclides with short half-lives, such as [60][61][62] Cu, were not detected in the examined sample. This supports the implementation of a1 2h time intervalb etweenE OB and EOP for eliminationo fa ny short-lived isotopes.…”
Section: Characterizationmentioning
confidence: 87%
“…This enzyme is expressed on various aggressively growing cancer cells, such as renal carcinoma, breast cancer, ovarian tumors, and gliomas . The 6A10 Fab has already been radiolabelled with 177 Lu and investigated for potential use as a radiotherapy agent against glioma recurrence . Further applications as a diagnostic tracer, radiolabelled with the PET nuclide 64 Cu, is now considered to extend the use of this biomolecule for tumor imaging.…”
Section: Introductionmentioning
confidence: 99%
“…[59] The 6A10 Fab has already been radiolabelledw ith 177 Lu and investigated for potentialu se as a radiotherapy agent against glioma recurrence. [60] Further applications as ad iagnostic tracer,r adiolabelled with the PET nuclide 64 Cu, is now considered to extendt he use of this biomolecule for tumor imaging.…”
Cu is a cyclotron-produced radionuclide which offers, thanks to its characteristic decay scheme, the possibility of combining positron emission tomography (PET) investigations with radiotherapy. We evaluated the Alceo system from Comecer SpA to automatically produce Cu for radiolabelling purposes. We established a Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody Fab fragment was successfully radiolabelled with the produced Cu, and proof-of-principle small-animal PET experiments on mice bearing glioma xenografts were performed. We obtained a high tumor-to-contralateral muscle ratio, which encourages further in vivo investigations of the radioconjugate regarding a possible application in diagnostic tumor imaging.
“…How the lack of exon 9 in CA12v2 affects its function is not known. Because CA12v2 is not expressed in normal brain, it may be a good target for glioblastomas expressing this variant [60]. Other interesting therapeutic targets for low-grade gliomas that were identified by our assay are NTRK2, ERBB3 and ERBB4.…”
Hundreds of biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer.Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals, leading to futile overtreatment. To acquire a comprehensive insight in aberrant actionable biological pathways in individual cancers we applied a costeffective targeted RNA next generation sequencing (NGS) technique. The test allows NGS-based measurement of transcript levels and splice variants of hundreds of genes with established roles in the biological behavior in many cancer types. We here present proof of concept that the technique generates a correct molecular diagnosis and a prognosis for glioma patients. The test not only confirmed known brain cancer-associated molecular aberrations but also identified aberrant expression levels of actionable genes and mutations that are associated with other cancer types. Targeted RNA-NGS is therefore a highly attractive method to guide precision therapy for the individual patient based on pathway analysis.
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