Enhancement of abnormal tissue uptake of antibodies, tumor-specific agents or conjugates thereof for diagnostic imaging or therapy
AssigneeUniversity of New Mexico
InventorsJerry L. Born, Dennis Eshima, Paul L. Mann, Nicholas A. Matwiyoff, Buck A. Rhodes
Life of this patent
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Abstract
Biomodulators, in conjunction with antibodies, tumor-specific agents or conjugates thereof, optionally linked to imaging-active moieties, can be administered to a host to enhance images thereof, e.g., NMR-, X-ray- or radioimages, preferably by increasing aberrant tissue signal intensity.
Claims15
A method of enhancing the delivery to abnormal tissue of an antibody-active agent which preferentially interacts with said abnormal tissue in comparison to neighboring normal tissue, comprising administering to a host a biomodulator and said active agent, the relative timing of the administration of each of the biomodulator and the active agent and their amounts being effective to enhance the preferential interaction of said active agent over neighboring normal tissue, wherein said biomodulator is a compound selected from CAD;
- swainsonine or an indolizidine alkaloid having an electronically similar 1,3-diol structure;
- ##STR6## having a 3S,5R;
- 3R,5R;
- or 3S,5S stereoconfiguration;
- pokeweed mitogen;
- Ukraine;
- or a compound of formula (I) ##STR7## wherein R.sup.10 is C.sub.1-6 -alkyl not containing an asymmetric carbon atom;
- each of R.sup.11 and R.sup.14 is, independently, H, C.sub.1-3 -alkyl, n-butyl, i-butyl, t-butyl, C.sub.1-3 -alkoxy, n-butoxy, i-butoxy, trifluoromethyl, fluoro, chloro, chloro, phenyl, phenoxy or benzyloxy;
- each of R.sup.12 and R.sup.15 is, independently, H, C.sub.1-3 -alkyl, C.sub.1-3 -alkoxy, trifluoromethyl, fluoro, chloro, chloro, phenyl, phenoxy or benzyloxy;
- each of R.sup.13 and R.sup.16 is, independently, H, C.sub.1-2 -alkyl, C.sub.1-2 -alkoxy, fluoro or chloro;
- with the provisos that not more than one of R.sup.11 and R.sup.12 is trifluoromethyl;
- not more than one of R.sup.11 and R.sup.12 is phenoxy;
- not more than one of R.sup.11 and R.sup.12 is benzyloxy;
- not more than one of R.sup.14 and R.sup.15 is trifluoromethyl;
- not more than one of R.sup.14 and R.sup.15 is phenoxy;
- not more than one of R.sup.14 and R.sup.15 is benzyloxy;
- R.sup.2 is --CH.sub.2 OH, --CHO, --COOR.sup.3, --COSR.sup.3, --CONR.sup.8 R.sup.9 or the corresponding lactone ##STR8## wherein R.sup.3 is H or C.sub.1-10 -alkyl,
- R.sup.4 and R.sup.5 are each independently H or C.sub.1-6 -alkyl,
- R.sup.6 and R.sup.7 are each independently OR, NHR or SR wherein R is H or C.sub.1-4 -alkanoyl,
- R.sup.8 and R.sup.9 are each independently H or C.sub.1-10 -alkyl, and
- X is C.sub.2-3 -alkylene, C.sub.2-3 -alkenylene, C.sub.2-3 -alkynylene, a cyclopropylene group, --OCH.sub.2 -- or --SCH.sub.2 --,
- wherein said compound is effective as a biomodulator.
A pharmaceutical kit comprising a container comprising a biomodulator and a separate container comprising an antibody or an antibody conjugated to an imaging or therapeutic agent, wherein said biomodulator is a compound selected from CAD;
- swainsonine or an indolizidine alkaloid having an electronically similar 1,3-diol structure;
- ##STR10## having a 3S,5R;
- 3R,5R;
- or 3S,5S stereoconfiguration;
- pokeweed mitogen;
- Ukraine;
- or a compound of formula (I) ##STR11## wherein R.sup.10 is C.sub.1-6 alkyl not containing an asymmetric carbon atom;
- each of R.sup.11 and R.sup.14 is, independently, H, C.sub.1-3 -alkyl, n-butyl, i-butyl, t-butyl, C.sub.1-3 -alkoxy, n-butoxy, i-butoxy, trifluormethyl, fluoro, chloro, chloro, phenyl, phenoxy or benzyloxy;
- each of R.sup.12 and R.sup.15 is, independently, H, C.sub.1-3 -alkyl, C.sub.1-3 alkoxy, trifluoromethyl, fluoro, chloro, chloro, phenyl, phenoxy or benzyloxy;
- each of R.sup.13 and R.sup.16 is, independently, H, C.sub.1-2 -alkyl, C.sub.1-2 -alkoxy, fluoro or chloro;
- with the provisos that not more than one of R.sup.11 and R.sup.12 is trifluoromethyl;
- not more than one of R.sup.11 and R.sup.12 is phenoxy;
- not more than one of R.sup.11 and R.sup.12 is benzyloxy;
- not more than one of R.sup.14 and R.sup.15 is trifluoromethyl;
- not more than one of R.sup.14 and R.sup.15 is phenoxy;
- not more than one of R.sup.14 and R.sup.15 is benzyloxy;
- R.sup.2 is --CH.sub.2 OH, --CHO, --COOR.sup.3, --COSR.sup.3, --CONR.sup.8 R.sup.9 or the corresponding lactone ##STR12## wherein R.sup.3 H or C.sub.1-10 -alkyl,
- R.sup.4 and R.sup.5 are each independently H or C.sub.1-6 -alkyl,
- R.sup.6 and R.sup.7 are each independently OR, NHR or SR wherein R is H or C.sub.1-4 -alkanoyl,
- R.sup.8 and R.sup.9 are each independently H or C.sub.1-10 -alkyl, and
- X is C.sub.2-3 -alkylene, C.sub.2-3 -alkenylene, C.sub.2-3 -alkynylene, a cyclopropylene group, --OCH.sub.2 -- or --SCH.sub.2 --,
- wherein said compound is effective as a biomodulator.
Dependencies are inferred from the claim text.