Linked Life Data

11280754

Source:http://linkedlifedata.com/resource/pubmed/id/11280754

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-3-30
pubmed:abstractText
The use of monoclonal antibodies (MAbs) directed against tumor-associated antigens for targeting of photosensitizers is an interesting option to improve the selectivity of photodynamic therapy (PDT). Hydrophilic photosensitizers are most suitable for conjugation to MAbs because of their water solubility. The photosensitizer aluminum (III) phthalocyanine tetrasulfonate [AlPc(SO3H)4] has many ideal photochemical properties; however, because of its hydrophilicity, the free form of this sensitizer does not readily reach the critical intracellular target and, therefore, is ineffective in PDT. On the basis of our previous studies, we hypothesized that AlPc(SO3H)4 might be suitable for PDT when coupled to internalizing tumor-selective MAbs. In this study, a reproducible procedure is presented for coupling of AlPc(SO3H)4 to MAbs via the tetra-glycine derivative AlPc(SO2Ngly)4. Conjugation was performed to chimeric MAb (cMAb) U36 and murine MAbs (mMAb) E48 and 425 using a labile ester. Conjugates showed preservation of integrity and immunoreactivity and full stability in serum in vitro. At molar ratios >4, the solubility of the conjugates decreased. Data on the in vitro efficacy of PDT showed that in the chosen experimental setup the internalizing AlPc(SO2Ngly)4-mMAb 425 conjugate was about 7500 times more toxic to A431 cells than the free sensitizer (IC50s, 0.12 nM versus 900 nM). The AlPc(SO2Ngly)4-mMAb 425 conjugate was also more toxic than meta-tetrahydroxyphenylchlorin-mMAb 425 conjugates and free meta-tetrahydroxyphenylchlorin that had been tested previously (M. B. Vrouenraets et al., Cancer Res., 59: 1505-1513, 1999) in the same system (IC50s, 7.3 nm and 2.0 nM, respectively). Biodistribution analysis of AlPc(SO2Ngly)4-125I-labeled cMAb U36 conjugates with different sensitizer:MAb ratios in squamous cell carcinoma-bearing nude mice revealed selective accumulation in the tumor, although to a lesser extent than for the unconjugated 125I-labeled cMAb U36, whereas tumor:blood ratios were similar. These findings indicate that AlPc(SO3H)4 has high potential for use in PDT when coupled to internalizing tumor-selective MAbs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1970-5
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:11280754-Animals, pubmed-meshheading:11280754-Antibodies, Monoclonal, pubmed-meshheading:11280754-Carcinoma, Squamous Cell, pubmed-meshheading:11280754-Head and Neck Neoplasms, pubmed-meshheading:11280754-Humans, pubmed-meshheading:11280754-Immunoconjugates, pubmed-meshheading:11280754-Immunotherapy, pubmed-meshheading:11280754-Indoles, pubmed-meshheading:11280754-Mice, pubmed-meshheading:11280754-Mice, Nude, pubmed-meshheading:11280754-Organometallic Compounds, pubmed-meshheading:11280754-Photochemotherapy, pubmed-meshheading:11280754-Quality Control, pubmed-meshheading:11280754-Radiation-Sensitizing Agents, pubmed-meshheading:11280754-Reproducibility of Results, pubmed-meshheading:11280754-Tissue Distribution, pubmed-meshheading:11280754-Xenograft Model Antitumor Assays
pubmed:year
2001
pubmed:articleTitle
Targeting of aluminum (III) phthalocyanine tetrasulfonate by use of internalizing monoclonal antibodies: improved efficacy in photodynamic therapy.
pubmed:affiliation
Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article