期刊
INVESTIGATIVE RADIOLOGY
卷 35, 期 1, 页码 50-57出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00004424-200001000-00006
关键词
folate; contrast agents; gadolinium; dendrimer; cancer
资金
- NCI NIH HHS [PHS-1-R29-CA61918] Funding Source: Medline
- NCRR NIH HHS [IS10RR06243, PHS-5-P41-RR05964] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R29CA061918, Z01SC010051] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR006243] Funding Source: NIH RePORTER
RATIONALE AND OBJECTIVES. Macromolecular contrast agents enhance tumors by means of active or passive targeting. Active targeting requires surface receptors, Many tumors of epithelial origin express the high-affinity folate receptor (hFR), including ovarian tumors, The objective of this research was to enhance tumors that express hFR using macromolecular contrast agents conjugated to folic acid. METHODS. The authors prepared a folate-conjugated dendrimer polychelate by attaching folic acid to a fourth-generation ammonia-core polyamidoamine dendrimer. The remaining amines were reacted with 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid. Relaxivity measurements (r(1) and r(2)) and MRI were conducted at 4.7 T. RESULTS. The dendrimer r(2) exceeded that of Gd-HP-DO3A by 8.2 times at 4.7 T, It increased the tumor percentage contrast enhancement, 24 hours after injection, of T2-weighted images by 33%, CONCLUSIONS. This new agent accumulates in turners expressing hFR, These results do not differentiate between active and passive targeting mechanisms, Receptor-negative tumors suggest a mechanism other than a nonspecific blood pool effect.
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