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December 23, 1950, Vol 144, No. 17 >
Other Articles | December 23, 1950

RADIOACTIVE DIIODOFLUORESCEIN IN DIAGNOSIS AND LOCALIZATION OF CENTRAL NERVOUS SYSTEM TUMORS

LOYAL DAVIS, M.D.; JOHN MARTIN, M.D.; MOSES ASHKENAZY, M.D.; GEORGE V. LeROY, M.D.; THEODORE FIELDS, B.S.
[+] Author Affiliations

Aided by the Grunow Surgical Fund.

The radioiodine used in this study was supplied by the Isotope Division, Oak Ridge National Laboratory, United States Atomic Energy Commission.

Reviewed in the Veterans Administration and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are the result of their own studies and do not necessarily reflect the opinion or policy of the Veterans Administration.


Chicago

From the Department of Surgery, Northwestern University Medical School, and the Veterans Administration Hospital Radioisotope Unit.


JAMA. 1950;144(17):1424-1432. doi:10.1001/jama.1950.02920170004003
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References

Radioactive diiodofluorescein has been utilized in the study of 200 patients with the diagnosis of a space-occupying lesion of the central nervous system. We have correlated our observations with the preoperative clinical diagnosis, electroencephalography, pneumography, angiography and surgical and autopsy observations. We have made postoperative and postirradiation tests and, finally, we have correlated all these studies with the histopathological characteristics of the tumors. The results indicate that this radioactive isotope dye test is a valuable diagnostic adjunct in neurosurgical problems not only because of its high degree of accuracy in determining the presence of brain tumors but also because of its relatively precise focal localization. The possibility of prognosticating in a general fashion the relative degree of cellularity and vascularity of the tumor also appears to be feasible.

Fluorescein was believed to have a special affinity for tumor cells as early as 1911, at which time Wasserman, Keysser and Wasserman

REFERENCES

1 +
Von Wasserman, A.; Keysser, F., and Wasserman, M.:  Beiträge zum Problem: Geschwülste von der Blutbahn aus therapeutisch zu beeinflussen; Auf Grund chemotherapeutischer Versuche an tumorkranken Tieren , Deutsche med. Wchnschr. 37:2389-2391, 1911;.
2 +
Copeman, S. M.; Coke, F., and Gouldesborough, C.:  Irradiated Fluorescein in Treatment of Cancer , Brit. M. J. 2: 233-236, 1929;.
3 +
Copeman, S. M.:  Activated (Irradiated) Fluorescein in Treatment of Cancer , Brit. M. J. 1:658-660, 1931;.
4 +
Crismon, J. M., and Fuhrman, F. A.:  Studies in Gangrene Following Cold Injury: Use of Fluorescein as Indicator of Local Blood Flow; Fluorescein Tests in Experimental Frosbite , J. Clin. Investigation 26:268-276, 1947;.
5 +
Gifford, H.:  Use of Fluorescein Intravenously as Aid to Ophthalmic Diagnosis and Treatment , Arch. Ophth. 24: 122-131 ( (July) ) 1940;.
6 +
Grafflin, A. L.:  Excretion of Fluorescein by Liver Under Normal and Abnormal Conditions, Observed in Vivo with Fluorescence Microscope , Am. J. Anat. 81:63-116, 1947;.
7 +
Katzenelbogen, S.: The Cerebrospinal Fluid and Its Relation to the Blood: A Physiological and Clinical Study , Baltimore, Johns Hopkins Press, 1935;.
8 +
Lange, K., and Boyd, L. J.:  Technique of Fluorescein Test to Determine Adequacy of Circulation in Peripheral Vascular Disease, Circulation Time and Capillary Permeability , Bull. New York M. Coll., Flower & Fifth Ave. Hosps. 6:78-81, 1943;.
9 +
Sicher, W. D.:  Circulation Time of Extremities Using Intravenous Fluorescein , Proc. Staff Meet., Mayo Clin. 18:515-521, 1943;.
10 +
Stocker, F. W.:  Experimental Studies on the Blood-Aqueous Barrier: II. Electrophotometric Measurements of Fluorescein Content of Aqueous After Intravenous Injection of Fluorescein, the Eye Being Under the Influence of Physostigmine, Pilocarpine, Neostigmine or Atropine , Arch. Ophth. 37: 583-590 ( (May) ) 1947;.
11 +
Wang, S. C.; Painter, E. E., and Overman, R. R.:  Fluorescein Circulation Time as Prognostic Sign in Experimental Traumatic Shock , J. Exper. Med. 84: 549-558, 1946;.
12 +
Ludford, R. J.:  Vital Staining of Normal and Malignant Cells: Staining of Malignant Tumors with Trypan Blue , Proc. Roy. Soc., London , s.B. 104:493-502, 1929;.
13 +
Duran-Reynals, F.:  Studies on Localization of Dyes and Foreign Proteins in Normal and Malignant Tissues , Am. J. Cancer 35: 98-107, 1939;;
14 +
 Localization of Foreign Proteins and Dyes in Neoplastic Growth , Proc. Soc. Exper. Biol. & Med. 36:369-370, 1937;.
15 +
Hess, M.:  Localization of Acid Azo-Dyes in Tumors , J. Path. & Bact. 51: 309-311, 1940;.
16 +
Boyland, E., and McClean, D.:  Factor in Malignant Tissues Which Increases Permeability of Dermis , J. Path. & Bact. 41:553-565, 1935;.
17 +
Stevens, C. D.; Lee, A.; Stewart, P H.; Quinlin, P. M., and Gilson, P. R.:  The Distribution of Radioactivity in Tumor-Bearing Mice After Injection of Radioactive Iodinated Trypan Blue , Cancer Research 9: 139-143, 1949;.
18 +
Broman, T.:  Supravital Analysis of Disorders in Cerebral Vascular Permeability in Man , Acta med. Scandinav. 118:79-83, 1944;.
19 +
Zahl, P. A., and Waters, L. L.:  Localization of Colloidal Dyes in Animal Tissues , Proc. Soc. Exper. Biol. & Med. 48:304-310, 1941;.
20 +
Shapiro, D. M., and Landing, B. M.:  Significance of Distribution of Fluorescein in Sarcoma in 180 Mice , Science 108: 304-306, 1948;.
21 +
Moore, G. E.:  Fluorescein as an Agent in the Differentiation of Normal and Malignant Tissues , Science 106: 130-131, 1947;.
22 +
Moore, G. E.; Peyton, W. T.; French, L. A., and Walker, W. W.:  Clinical Use of Fluorescein in Neurosurgery: Localization of Brain Tumors , J. Neurosurg. 5:392-398, 1948;.
23 +
Moore, G. E.; Hunter, S. W., and Hubbard, T. B.:  Clinical and Experimental Studies of Fluorescein Dyes with Special Reference to Their Use for the Diagnosis of Central Nervous System Tumors , Ann. Surg. 130:637-642, 1949;.
24 +
Marvin, J. F., and Moore, G. E.: Localization of Brain Tumors with Radiodye: II. Experimental Evaluation of Physical Limitations, Nucleonics , 1948;, vol. 3, no. (4) , pp. 63-65.
25 +
Moore, G. E.:  Use of Radioactive Di-Iodo-Fluorescein in Diagnosis and Localization of Brain Tumors , Science 107:569-571, 1948;.
26 +
Tabern, D. L.: Personal communication to the author.
27 +
Davis, L.; Martin, J.; Goldstein, S. L., and Ashkenazy, M.:  A Study of 211 Patients with Verified Glioblastoma Multiforme , J. Neurosurg. 6: 33-44. 1949;.
28 +
Davis, L., and Weil, A.:  The Effect of Radiation Therapy upon Intracranial Gliomata , Ann. Surg. 106:544-616, 1937;.

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1 +
Von Wasserman, A.; Keysser, F., and Wasserman, M.:  Beiträge zum Problem: Geschwülste von der Blutbahn aus therapeutisch zu beeinflussen; Auf Grund chemotherapeutischer Versuche an tumorkranken Tieren , Deutsche med. Wchnschr. 37:2389-2391, 1911;.
2 +
Copeman, S. M.; Coke, F., and Gouldesborough, C.:  Irradiated Fluorescein in Treatment of Cancer , Brit. M. J. 2: 233-236, 1929;.
3 +
Copeman, S. M.:  Activated (Irradiated) Fluorescein in Treatment of Cancer , Brit. M. J. 1:658-660, 1931;.
4 +
Crismon, J. M., and Fuhrman, F. A.:  Studies in Gangrene Following Cold Injury: Use of Fluorescein as Indicator of Local Blood Flow; Fluorescein Tests in Experimental Frosbite , J. Clin. Investigation 26:268-276, 1947;.
5 +
Gifford, H.:  Use of Fluorescein Intravenously as Aid to Ophthalmic Diagnosis and Treatment , Arch. Ophth. 24: 122-131 ( (July) ) 1940;.
6 +
Grafflin, A. L.:  Excretion of Fluorescein by Liver Under Normal and Abnormal Conditions, Observed in Vivo with Fluorescence Microscope , Am. J. Anat. 81:63-116, 1947;.
7 +
Katzenelbogen, S.: The Cerebrospinal Fluid and Its Relation to the Blood: A Physiological and Clinical Study , Baltimore, Johns Hopkins Press, 1935;.
8 +
Lange, K., and Boyd, L. J.:  Technique of Fluorescein Test to Determine Adequacy of Circulation in Peripheral Vascular Disease, Circulation Time and Capillary Permeability , Bull. New York M. Coll., Flower & Fifth Ave. Hosps. 6:78-81, 1943;.
9 +
Sicher, W. D.:  Circulation Time of Extremities Using Intravenous Fluorescein , Proc. Staff Meet., Mayo Clin. 18:515-521, 1943;.
10 +
Stocker, F. W.:  Experimental Studies on the Blood-Aqueous Barrier: II. Electrophotometric Measurements of Fluorescein Content of Aqueous After Intravenous Injection of Fluorescein, the Eye Being Under the Influence of Physostigmine, Pilocarpine, Neostigmine or Atropine , Arch. Ophth. 37: 583-590 ( (May) ) 1947;.
11 +
Wang, S. C.; Painter, E. E., and Overman, R. R.:  Fluorescein Circulation Time as Prognostic Sign in Experimental Traumatic Shock , J. Exper. Med. 84: 549-558, 1946;.
12 +
Ludford, R. J.:  Vital Staining of Normal and Malignant Cells: Staining of Malignant Tumors with Trypan Blue , Proc. Roy. Soc., London , s.B. 104:493-502, 1929;.
13 +
Duran-Reynals, F.:  Studies on Localization of Dyes and Foreign Proteins in Normal and Malignant Tissues , Am. J. Cancer 35: 98-107, 1939;;
14 +
 Localization of Foreign Proteins and Dyes in Neoplastic Growth , Proc. Soc. Exper. Biol. & Med. 36:369-370, 1937;.
15 +
Hess, M.:  Localization of Acid Azo-Dyes in Tumors , J. Path. & Bact. 51: 309-311, 1940;.
16 +
Boyland, E., and McClean, D.:  Factor in Malignant Tissues Which Increases Permeability of Dermis , J. Path. & Bact. 41:553-565, 1935;.
17 +
Stevens, C. D.; Lee, A.; Stewart, P H.; Quinlin, P. M., and Gilson, P. R.:  The Distribution of Radioactivity in Tumor-Bearing Mice After Injection of Radioactive Iodinated Trypan Blue , Cancer Research 9: 139-143, 1949;.
18 +
Broman, T.:  Supravital Analysis of Disorders in Cerebral Vascular Permeability in Man , Acta med. Scandinav. 118:79-83, 1944;.
19 +
Zahl, P. A., and Waters, L. L.:  Localization of Colloidal Dyes in Animal Tissues , Proc. Soc. Exper. Biol. & Med. 48:304-310, 1941;.
20 +
Shapiro, D. M., and Landing, B. M.:  Significance of Distribution of Fluorescein in Sarcoma in 180 Mice , Science 108: 304-306, 1948;.
21 +
Moore, G. E.:  Fluorescein as an Agent in the Differentiation of Normal and Malignant Tissues , Science 106: 130-131, 1947;.
22 +
Moore, G. E.; Peyton, W. T.; French, L. A., and Walker, W. W.:  Clinical Use of Fluorescein in Neurosurgery: Localization of Brain Tumors , J. Neurosurg. 5:392-398, 1948;.
23 +
Moore, G. E.; Hunter, S. W., and Hubbard, T. B.:  Clinical and Experimental Studies of Fluorescein Dyes with Special Reference to Their Use for the Diagnosis of Central Nervous System Tumors , Ann. Surg. 130:637-642, 1949;.
24 +
Marvin, J. F., and Moore, G. E.: Localization of Brain Tumors with Radiodye: II. Experimental Evaluation of Physical Limitations, Nucleonics , 1948;, vol. 3, no. (4) , pp. 63-65.
25 +
Moore, G. E.:  Use of Radioactive Di-Iodo-Fluorescein in Diagnosis and Localization of Brain Tumors , Science 107:569-571, 1948;.
26 +
Tabern, D. L.: Personal communication to the author.
27 +
Davis, L.; Martin, J.; Goldstein, S. L., and Ashkenazy, M.:  A Study of 211 Patients with Verified Glioblastoma Multiforme , J. Neurosurg. 6: 33-44. 1949;.
28 +
Davis, L., and Weil, A.:  The Effect of Radiation Therapy upon Intracranial Gliomata , Ann. Surg. 106:544-616, 1937;.

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