Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target.

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Hdl Handle:
http://hdl.handle.net/10541/77834
Title:
Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target.
Authors:
Costello, Brendan; Li, Chenggang; Duff, Sarah E; Butterworth, David; Khan, Ali; Perkins, Michael; Owens, Susan E; Al-Mowallad, Abdul Fattah; O'Dwyer, Sarah T; Kumar, Shant
Abstract:
There is strong published and unpublished evidence that our CD105 Mab E9, which is highly reactive with angiogenic endothelial cells, could be a useful reagent to target the vasculature of solid tumors in man. Since Mab E9 does not cross-react with animal tissues, we undertook here to evaluate its localization using human kidney as an ex vivo model. Perfusion was performed through the renal artery of 99Tcm-labeled purified CD105 Mab in freshly excised kidneys from 7 patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the presence of well-defined radioactive hot spots, which matched the positions of the tumors as identified by presurgery MRI scans and subsequent histopathologic examination. Importantly, in one instance, where a presurgery MRI scan had identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of radioactivity. The pathology report confirmed that the additional hot spot corresponded to a small secondary well-vascularized tumor. The implication of this finding is that the radiolabeled Mab, E9, may be of use in the detection of metastatic disease. That the labeling of tumors was specific was confirmed when prior perfusion of unlabeled mab E9 in 2 kidneys completely blocked the localization of 99Tcm-conjugated Mab E9. Radioactivity in samples of tumor and normal tissue taken from 7 kidneys was counted in a gamma counter. In all cases, there was a greater uptake of radioactivity in tumors compared with the corresponding normal kidneys. The median values, adjusted per gram wet weight, for 99Tcm were 14.8 times (range, 4.8-113.0) greater in kidney tumors than in normal kidney tissue (p < 0.007). Immunofluorescent staining of cryostat sections of tumor tissues in each of the 7 cases showed strong and uniform localization of Mab E9 in tumor microvessels. Interestingly, chimeric staining of endothelial cells (ECs) was seen in an occasional microvessel segment. That is, while most of the ECs lining a microvessel were strongly stained, an occasional EC was negative. This was not an artifact of staining. Unstained ECs may be nonangiogenic or apoptotic since CD105 is a proliferation/activation-associated antigen. Further investigations are warranted to establish the pharmacokinetics of 99Tcm-labeled CD105 antibody in vivo. This would enable us to determine whether an apparently highly successful ex vivo study has the potential for tumor imaging/therapeutic vascular targeting in patients with cancer.
Affiliation:
North Manchester General Hospital, Manchester, United Kingdom.
Citation:
Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target. 2004, 109 (3):436-41 Int. J. Cancer
Journal:
International Journal of Cancer.
Issue Date:
10-Apr-2004
URI:
http://hdl.handle.net/10541/77834
DOI:
10.1002/ijc.11699
PubMed ID:
14961584
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorCostello, Brendan-
dc.contributor.authorLi, Chenggang-
dc.contributor.authorDuff, Sarah E-
dc.contributor.authorButterworth, David-
dc.contributor.authorKhan, Ali-
dc.contributor.authorPerkins, Michael-
dc.contributor.authorOwens, Susan E-
dc.contributor.authorAl-Mowallad, Abdul Fattah-
dc.contributor.authorO'Dwyer, Sarah T-
dc.contributor.authorKumar, Shant-
dc.date.accessioned2009-08-19T11:14:36Z-
dc.date.available2009-08-19T11:14:36Z-
dc.date.issued2004-04-10-
dc.identifier.citationPerfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target. 2004, 109 (3):436-41 Int. J. Canceren
dc.identifier.issn0020-7136-
dc.identifier.pmid14961584-
dc.identifier.doi10.1002/ijc.11699-
dc.identifier.urihttp://hdl.handle.net/10541/77834-
dc.description.abstractThere is strong published and unpublished evidence that our CD105 Mab E9, which is highly reactive with angiogenic endothelial cells, could be a useful reagent to target the vasculature of solid tumors in man. Since Mab E9 does not cross-react with animal tissues, we undertook here to evaluate its localization using human kidney as an ex vivo model. Perfusion was performed through the renal artery of 99Tcm-labeled purified CD105 Mab in freshly excised kidneys from 7 patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the presence of well-defined radioactive hot spots, which matched the positions of the tumors as identified by presurgery MRI scans and subsequent histopathologic examination. Importantly, in one instance, where a presurgery MRI scan had identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of radioactivity. The pathology report confirmed that the additional hot spot corresponded to a small secondary well-vascularized tumor. The implication of this finding is that the radiolabeled Mab, E9, may be of use in the detection of metastatic disease. That the labeling of tumors was specific was confirmed when prior perfusion of unlabeled mab E9 in 2 kidneys completely blocked the localization of 99Tcm-conjugated Mab E9. Radioactivity in samples of tumor and normal tissue taken from 7 kidneys was counted in a gamma counter. In all cases, there was a greater uptake of radioactivity in tumors compared with the corresponding normal kidneys. The median values, adjusted per gram wet weight, for 99Tcm were 14.8 times (range, 4.8-113.0) greater in kidney tumors than in normal kidney tissue (p < 0.007). Immunofluorescent staining of cryostat sections of tumor tissues in each of the 7 cases showed strong and uniform localization of Mab E9 in tumor microvessels. Interestingly, chimeric staining of endothelial cells (ECs) was seen in an occasional microvessel segment. That is, while most of the ECs lining a microvessel were strongly stained, an occasional EC was negative. This was not an artifact of staining. Unstained ECs may be nonangiogenic or apoptotic since CD105 is a proliferation/activation-associated antigen. Further investigations are warranted to establish the pharmacokinetics of 99Tcm-labeled CD105 antibody in vivo. This would enable us to determine whether an apparently highly successful ex vivo study has the potential for tumor imaging/therapeutic vascular targeting in patients with cancer.en
dc.language.isoenen
dc.subjectRenal Canceren
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntigens, CD-
dc.subject.meshCarcinoma, Renal Cell-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshHumans-
dc.subject.meshKidney Neoplasms-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshPerfusion-
dc.subject.meshRadioimmunodetection-
dc.subject.meshReceptors, Cell Surface-
dc.subject.meshTechnetium-
dc.subject.meshVascular Cell Adhesion Molecule-1-
dc.titlePerfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target.en
dc.typeArticleen
dc.contributor.departmentNorth Manchester General Hospital, Manchester, United Kingdom.en
dc.identifier.journalInternational Journal of Cancer.en
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