Effect of Polar Head Group Modifications on the Tumor Retention of Phospholipid Ether Analogs: Role of the Quaternary Nitrogen.
Effect of Polar Head Group Modifications on the Tumor Retention of Phospholipid Ether Analogs: Role of the Quaternary Nitrogen.
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DOI：
10.3390/pharmaceutics15010171
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发表时间：
2023-01-03
期刊：
影响因子：
5.4
通讯作者：
Weichert JP
中科院分区：
文献类型：
--
作者：
Pinchuk AN;Rampy MA;Longino MA;Durkee BY;Counsell RE;Weichert JP
We have previously described the remarkable capacity of radioiodinated alkyl phospholipids to be sequestered and retained by a variety of tumors in vivo. We have already established the influence of certain structural parameters of iodinated alkyl phospholipids on tumor avidity, such as stereochemistry at the sn-2 carbon of alkylglycerol phosphocholines, meta-or para-position of iodine in the aromatic ring of phenylalkyl phosphocholines, and the length of the alkyl chain in alkyl phospholipids. In order to determine the additional structural requirements for tumor uptake and retention, three new radioiodinated alkylphospholipid analogs, 2–4, were synthesized as potential tumor imaging agents. Polar head groups were modified to determine structure-tumor avidity relationships. The trimethylammonio group in 1 was substituted with a hydrogen atom in 2, an ammonio group in 3 and a tertiary butyl group in 4. All analogs were separately labeled with iodine-125 or iodine-124 and administered to Walker 256 tumor-bearing rats or human PC-3 tumor-bearing SCID mice, respectively. Tumor uptake was assessed by gamma-camera scintigraphy (for [I-125]-labeled compounds) and high-resolution micro-PET scanning (for [I-124]-labeled compounds). It was found that structural modifications in the polar head group of alkyl phospholipids strongly influenced the tumor uptake and tissue distribution of these compounds in tumor-bearing animals. Phosphoethanolamine analog 3 (NM401) displayed a very slight accumulation in tumor as compared with phosphocholine analog 1 (NM346). Analogs 2 (NM400) and 4 (NM402) lacking the positively charged nitrogen atom failed to display any tumor uptake and localized primarily in the liver. This study provided important insights regarding structural requirements for tumor uptake and retention. Replacement of the quaternary nitrogen in the alkyl phospholipid head group with non-polar substituents resulted in loss of tumor avidity.
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影响因子：
5
作者：
Nachtigal MW;Musaphir P;Dhiman S;Altman AD;Schweizer F;Arthur G
通讯作者：
Arthur G
影响因子：
17.1
作者：
Patel RB;Hernandez R;Carlson P;Grudzinski J;Bates AM;Jagodinsky JC;Erbe A;Marsh IR;Arthur I;Aluicio-Sarduy E;Sriramaneni RN;Jin WJ;Massey C;Rakhmilevich AL;Vail D;Engle JW;Le T;Kim K;Bednarz B;Sondel PM;Weichert J;Morris ZS
通讯作者：
Morris ZS
影响因子：
3.6
作者：
LINDH, I;STAWINSKI, J
通讯作者：
STAWINSKI, J
影响因子：
2.7
作者：
Brachwitz, H;Olke, M;Langen, P
通讯作者：
Langen, P
影响因子：
9.3
作者：
Grudzinski, Joseph J.;Hernandez, Reinier;Weichert, Jamey
通讯作者：
Weichert, Jamey