Phosphorescent dendritic macromolecular compounds for imaging tissue oxygen

• US 5,837,865 A
• Filed: 12/16/1996
• Issued: 11/17/1998
• Est. Priority Date: 10/15/1993
• Status: Expired due to Term

• Current Assignee: Oxygen Enterprises, Ltd.
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Vinogradov, Sergei A., Wilson, David F.
• Primary Examiner(s): Shah, Mukund
• Assistant Examiner(s): Sripada, Pavanaram K.
• Application Number:
  US08/767,158
• Time in Patent Office: 701 Days
• Field of Search: 540/145, 128/654
• US Class Current: 540/145
• CPC Class Codes: A61B 2562/146 for optical coupling
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/14556 by fluorescence A61B5/14555 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07H 15/26 Acyclic or carbocyclic radicals, substituted by hetero rings
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 31/225 for oxygen, e.g. including dissolved oxygen

Abstract

This invention relates to phosphorescent probes effective for oxygen measurement in human or animal tissue comprising a porphyrin chromophore capable of releasing absorbed energy as phosphorescent light and a dendrimer, wherein said porphyrin chromophore comprises the core of the dendrimer.

Claims

1. A phosphorescent probe effective for oxygen measurement in human or animal tissue comprising a porphyrin chromophore capable of releasing absorbed energy as phosphorescent light and a dendrimer, wherein said porphyrin chromophore comprises the core of the dendrimer.

2. The phosphorescent probe of claim 1 wherein the absorption spectrum of the chromophore exhibits strong light absorption in the near infrared region of the spectrum where natural tissue chromophores exhibit relatively weak absorption.

3. The phosphorescent probe of claim 1 wherein the absorption spectrum of the chromophore exhibits strong light absorption at from between about 600 nm to about 720 nm.

4. The phosphorescent probe of claim 1 wherein the absorption spectrum of the chromophore exhibits strong light absorption at from between about 610 nm to about 720 nm.

5. The phosphorescent probe of claim 1 wherein the porphyrin chromophore comprises a functionally derivatized metalloporphyrin.

6. The functionally derivitized metalloporphyrin of claim 5 which has the formula:

##STR5## wherein;

R₁ is a hydrogen atom or a substituted or unsubstituted aryl;

R₂ and R₃ are independently hydrogen or are linked together to form substituted or unsubstituted aryl; and

M is H₂ or a metal.

7. The compound of claim 6 wherein M is a metal selected from the group consisting of Zn, Al, Sn, Y, La, Lu, Pd, Pt and derivatives thereof.

8. The compound of claim 5 wherein the porphyrin is selected from the group consisting of tetrabenzoporphyrin, tetranapthoporphyrin, tetraanthraporphyrin, and derivatives thereof.

9. The compound of claim 8 wherein the metal is selected from the group consisting of Zn, Al, Sn, Y, La, Lu, Pd, Pt and derivatives thereof.

10. The compound of claim 9 wherein the derivative is a meso-tetraphenylated compound.

11. The compound of claim 10 wherein the metalloporphyrin is tetraphenyltetrabenzoporphyrin.

12. The compound of claim 10 wherein the metalloporphyrin is (Lu) tetraphenyltetranapthoporphyrin.

13. The compound of claim 10 wherein the metalloporphyrin is meso-tetra-(4-carboxylphenyl)porphyrin.

14. The compound of claim 10 which is meso-tetraphenyltetrabenzoporphyrin.

15. The compound of claim 10 which is meso-tetraphenyltetranapthoporphyrin.

16. The compound of claim 8 wherein the porphyrin is tetrabenzoporphyrin.

17. The compound of claim 10 wherein said dendrimer is a first, second, third, fourth or fifth generation dendrimer.

18. The compound of claim 17 wherein said dendrimer comprises polyglutamate dendritic cages.