Phospholipid ether analogs for imaging and targeted treatment of pediatric solid tumors
It is disclosed herein that that certain alkylphosphocholine analogs are preferentially taken up by malignant pediatric tumor cells. The alkylphophocholine analogs are compounds having the formula: or salts thereof, wherein n is an integer from 12 to 24; and R 2 is —N + (CH 3 ) 3 . The compounds can be used to treat pediatric solid tumors or to detect pediatric solid tumors. In therapeutic treatment, R 1 includes a radioactive iodine isotope that locally delivers therapeutic dosages of radiation to the malignant pediatric tumor cells that preferentially take up the compound. In detection/imaging applications, R 1 includes a detection moiety, such as a fluorophore or a radioactive iodine isotope.
1. A method for treating a malignant pediatric solid tumor in a subject, comprising administering to a subject having a malignant pediatric solid tumor an effective amount of a compound having the formula:
or a salt thereof, wherein:
R 1 is a radioactive iodine isotope;
n is an integer from 12 to 24; and
R 2 is —N + (CH 3 ) 3 ;
whereby the malignant pediatric solid tumor is a rhabdomyosarcoma (RMS) tumor treated in the subject.
2. The method of claim 1 , wherein the radioactive iodine isotope is selected from the group consisting of 123 I, 125 I and 131 I.
3. The method of claim 1 , wherein n is 18, and the radioactive iodine isotope is 123 I, 125 I, or 131 I (the compound is [ 123 I]—CLR1404, [ 125 I]—CLR1404 or [131I]—CLR1404).
4. The method of claim 1 , wherein the compound is administered by parenteral, intranasal, sublingual, rectal, or transdermal delivery.
5. A method for inhibiting the proliferation or growth of malignant pediatric solid tumor cells, comprising contacting one or more malignant pediatric solid tumor cells with an effective amount of a compound having the formula:
or a salt thereof, wherein:
R 1 is a radioactive iodine isotope;
n is an integer from 12 to 24; and
R 2 is —N + (CH 3 ) 3 ;
whereby growth or proliferation the malignant pediatric solid tumor cells is a rhabdomyosarcoma (RMS) tumor, wherein said tumor is inhibited.
6. The method of claim 5 , wherein the radioactive iodine isotope is selected from the group consisting of 123 I, 125 I and 131 I.
7. The method of claim 5 , wherein n is 18, and the radioactive iodine isotope is 123 I, 125 I, or 131 I (the compound is [ 123 I]—CLR1404, [ 125 I]—CLR1404 or [ 131 I]—CLR1404).