Radiolabeled lymphatic staining agents and methods for making

Abstract

A radiolabeled lymphatic staining agent is mixed on site with a much larger amount, on a weight basis, of a non-radiolabeled lymphatic staining agent to form an injectable radiolabeled lymphatic staining agent suitable for surgical use in humans. Preferably, the radiolabel is I-125, because it has a 60-day half-life which enables it to be made off-site. The preferred radiolabeled lymphatic staining agent is iodinated methylene blue, because it can be mixed with a range of non-radioactive lymphatic staining agents, for example isosulfan blue, methylene blue, patent blue, and patent blue V, to provide the injected agent with sufficient radioactivity to enable machine detection. A method for making radioiodinated methylene blue is also disclosed.

1 . A composition of matter selected from the group consisting of phenothiazin-5-ium,3,7-bis(dimethylamino)-iodide; 4-iodo-phenothiazin-5-ium,3,7-bis(dimethylamino)-chloride; 4-iodo-phenothiazin-5-ium,3,7-bis(dimethylamino)-iodide; 4,6-diiodo-phenothiazin-5-ium,3,7-bis(dimethylamino)-chloride; 4,6-diiodo-phenothiazin-5-ium,3,7-bis(dimethylamino)-iodide, 4,6-diiodo-phenothiazin-5-ium,3,7-bis(methylantino)-chloride and 4-iodo-phenothiazin-5-ium,3 (methylamino), 7(dimethylamino)-chloride 
   
   
       2 . A composition of matter as in  claim 1  in which a substantial portion of the iodine is selected from the group consisting of Iodine-125 isotope and Iodine-131 isotope. 
   
   
       3 . A composition of matter as in  claim 2  further comprising a near-neutral salt solution. 
   
   
       4 . A composition of matter as in  claim 3  further comprising a minor amount of phenothiazin-5-ium,3,7-bis(dimethylamino)-chloride and a major amount of a lymphatic staining agent having a high affinity for lymphatic tissue. 
   
   
       5 . A method for providing an injectable radiolabeled lymphatic staining agent, said method comprising
 selecting a lymphatic staining agent,   radiolabeling said selected lymphatic staining agent to form a radiolabeled lymphatic staining agent,   shipping said radiolabeled lymphatic staining agent to a hospital,   mixing said radiolabeled lymphatic staining agent at the hospital with a much larger amount, on a weight basis, of a non-radiolabeled lymphatic staining agent to form an injectable radiolabeled lymphatic staining agent suitable for surgical use in humans.   
   
   
       6 . A method as in  claim 5  wherein
 said selected lymphatic staining agent is radiolabeled with a radioisotope having a half-life in the range of from 2 days to 2 years.   
   
   
       7 . A method as in  claim 5  wherein said radioisotope is selected from the group consisting of Iodine-131 and Iodine-125. 
   
   
       8 . A method as in  claim 5  wherein said radioisotope comprises Iodine-125. 
   
   
       9 . A method as in  claim 5  wherein said selected lymphatic staining agent comprises methylene blue. 
   
   
       10 . A method as in  claim 5  wherein the much larger amount of a non-radiolabeled lymphatic staining agent is selected from the group consisting of isosulfan blue, methylene blue, patent blue, and patent blue V. 
   
   
       11 . A method as in  claim 5  wherein the much larger amount of the non-radiolabeled lymphatic staining agent is isosulfan blue. 
   
   
       12 . A method as in  claim 5  wherein the selected lymphatic staining agent has a lower affinity for lymphatic tissue than the much larger amount of the non-radiolabeled lymphatic staining agent