Radioiodinated ether phospholipid analogs as potential tumor-specific imaging agents.
Meyer, Karen Lynn
1988
Abstract
Radioiodinated analogs of the naturally-occurring alkyl lysophospholipid (ALP) were designed and synthesized for evaluation as potential tumor-specific imaging agents. Tumor-specific imaging agents are radiopharmaceuticals which localize within a tumor and thereby provide a positive image of the tumor. In order to achieve this selective accumulation, the ALP analogs chosen for synthesis were based on an understanding of the biochemical synthesis and/or metabolism of natural ether phospholipids and the pharmacological actions of synthetic analogs. The five iodinated ALP analogs synthesized were rac-1-O- (12-(m-iodophenyl)dodecyl) glycero-3-phosphocholine, ET-12IP-OH; rac-1-O- (12-(m-iodophenyl)dodecyl) -2-O-methylglycero-3-phosphocholine, ET-12IP-OMe; rac-1-O- (12-(m-iodophenyl)dodecyl) propane-1,3-diol-3-phosphocholine, ET-12IP-H; rac-1-O-hexadecyl-2-O-(m-iodobenzoyl)glycero-3-phosphocholine, ET-16-IBz and rac-1-O-hexadecyl-2-O-(m-iodobenzyl)-glycero-3-phosphocholine, ET-16-IBn. Four analogs, ET-12IP-OMe, ET-12IP-H, ET-16-IBz and ET-16-IBn were radiolabelled with iodine-125 in moderate yields via an isotope exchange procedure. ($\sp{125}$I) ET-12IP-OMe, ($\sp{125}$I) ET-12IP-H and ($\sp{125}$I) ET-16-IBz were evaluated in tissue distribution (TD) studies involving both normal and tumor-bearing rats. The tumor chosen for this study was the Walker 256 sarcoma which was implanted in the thigh. The TD results revealed that the radiolabelled ALP analogs exhibited different accumulation patterns. Following intravenous (IV) administration of ($\sp{125}$I) ET-12IP-OMe and ($\sp{125}$I) ET-12IP-H, an immediate and sustained uptake of radioactivity within the tumor was observed with the greatest accumulation of radioactivity appearing after administration of ($\sp{125}$I) ET-12IP-OMe. In contrast, a much slower and lower accumulation of radioactivity within the tumor was found for ($\sp{125}$I) ET-16-IBz. Although, clearance of radioactivity from the nontarget tissues occurred with time, clearance in the tumor was delayed for ($\sp{125}$I) ET-12IP-OMe and ($\sp{125}$I) ET-12IP-H. This difference in clearance from the tumor vis-a-vis other tissues afforded an appropriate tumor to nontumor ratio. On the other hand, the level of radioactivity within the tumor following administration of ($\sp{125}$I) ET-16-IBz was not appreciably different from that of normal tissues. Based upon the TD results and the tumor to nontumor ratios, ($\sp{125}$I) ET-12IP-OMe was selected for scintigraphic studies with rats bearing the Walker 256 sarcoma. Twenty-four hours following administration of the radiolabeled ALP analog, external imaging with a gamma-camera clearly delineated the tumor.Subjects
Agents Analogs Ether Imaging Phospholipid Potential Radioiodinated Specific Tumor
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