Processes synthesize sulfonated and nonsulfonated uranyl phthalocyanines for application in neutron therapy of brain tumors. Tests indicate that the compounds are advantageous over the previously used boron and lithium compounds

Frigerio, N. A.

English

NASA Technical Reports Server

June 1967	 Brief 67-10188 
•II2	 AEC-NASA TECH BRIEF 
AEC-NASA Tech Briefs describe innovations resulting from the research and development program 
of the U.S. AEC or from AEC-NASA interagency efforts. They are issued to encourage commercial 
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the Clearinghouse for Federal Scientific and Technical Information, Springfield, Virginia 22151. 
Uranyl Phthalocyanines Show Promise in the Treatment of Brain Tumors 
The problem: 
To devise a process for synthesizing sulfonated and 
nonsulfonated uranyl phthalocyanines. These are 
stable, nontoxic uranyl compounds which have shown 
promise as fissionable materials for the neutron ther-
apy of brain tumors. 
The solution: 
Two new processes have been developed for syn-
thesizing uranyl phthalocyanine and sulfonated uranyl 
phthalocyanine. Tests conducted on laboratory animals 
to determine the effectiveness of these compounds in 
treating brain tumors indicate that the compounds 
offer a number of advantages over the boron and 
lithium compounds that have been used previously for 
this treatment. 
How it's done: 
The water-insoluble uranyl phthalocyanines are 
made by mixing an inorganic uranyl salt, such as 
uranyl nitrate hexahydrate or uranyl chloride, with a 
Lewis-base-type nitrogen or sulfur-containing organic 
compound, such as dimethyl formamide (DMF) or 
methyl sulfoxide. This mixture causes the following 
reaction:
U0(NO) 2 • 6H2 0 + 2DMF—* 
UO2 (NO3 ) 2 • 2DMF + 6H20 
In this reaction a water-free complex is formed be-
tween the uranyl salt and the organic compound. The 
uranyl compound is then separated from the liquid 
and mixed with a stoichiometric quantity of lithium 
phthalocyanine at room temperature under anhydrous 
conditions, forming a uranyl salt according to the 
following equation: 
Li2Pc + UO2(NO•2DMF—* 
UO2Pc + 2LiNO3 + 2DMF
The uranyl phthalocyanine is isolated from the re-
action mixture as a crystalline precipitate. Metal 
phthalocyanines of sodium, potassium, magnesium, or 
beryllium can also be used in this synthesis in place 
of the lithium phthalocyanine. 
Sulfonated uranyl phthalocyanine can be synthe-
sized by mixing sulfonated phthalocyanine in a water 
solution with a water-soluble salt such as. uranyl sul-
fate and then boiling the solution for about three 
hours. This causes the uranyl radical to replace the 
hydrogen ions bound in the sulfonated phthalocyanine. 
The precipitate formed in this reaction is filtered off 
and suspended in water, through which hydrogen sul-
fide is bubbled, and the mixture is then refluxed. The 
uranyl precipitate is evaporated from this solution 
after filtering off the black precipitate with which it 
was mixed. The sulfonated uranyl phthalocyanine 
compounds prepared by this method are water soluble 
and can be purified with anion exchange resins. 
These sulfonated or nonsulfonated monouranyl 
phthalocyanines contain fissionable uranium isotopes 
but are chemically nontoxic. The uranyl radical is 
bonded in the molecule so strongly that its dissocia-
tion cannot be detected analytically. 
Both of these uranyl compounds have been found 
to be very effective in the treatment of locatable 
tumors in laboratory animals. A colloidal suspension 
of the insoluble uranyl phthalocyanine can be injected 
directly into the tumor of the animal. Bombardment 
with slow neutrons will then produce radiation to 
destroy the tumor. With the uranyl compounds of 
fissionable isotopes, not only gamma rays but also 
fission fragments of high energy levels are obtained. 
The sulfonated water-soluble compounds can also 
be injected directly into a brain tumor in a laboratory 
(continued overleaf) 
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Administration. Neither the United States Government nor any per- method, or process disclosed in this document may not infringe pri-
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animal, and bombarded with neutrons to produce 
radiation. It was found that the healthy brain tissue 
of laboratory animals rejects these compounds while 
the tumor tissue retains them. Within minutes the ratio 
of compound in the tumor to that in the healthy 
tissue is 50: 1. The neutron bombardment is relatively 
harmless to any tissue other than the tumor tissue 
because of the small concentration of the phthalocy-
anine in the healthy tissue. When the tumor is bom-
barded with neutrons the ranges of the particles 
formed are 40-100 microns, thus damage to healthy 
tissue surrounding the tumor should be less than that 
caused by surgery. 
The preferential concentration of the uranyl phtha-
locyanines in the tumor tissue affords a considerable 
advantage over the use of lithium and boron com-
pounds previously employed, as these do not concen-
trate well in the brain tumor tissues. 
Notes: 
1. Additional details are contained in: 
a. Patent #3,027,391, available from U.S. Patent 
Office; $0.50 each. 
b. "Recent Developments in the Theory of Neu-
tron Capture Theory," ANL-6910. This report 
is available from the Clearinghouse for Scienti-
fic and Technical Information, Springfield, Vir-
ginia 22151; price $1.00.
2. Inquiries concerning this innovation may be di-
rected to:
Office of Industrial Cooperation 
Argonne National Laboratory 
9700 South Cass Avenue 
Argonne, Illinois 60439 
Reference: B67-10188 
Source: N. A. Frigerio
Biological & Medical Research Division 
(ARG-100) 
Patent status: 
Inquiries about obtaining rights for commercial use 
of this innovation may be made to: 
Mr. George H. Lee, Chief 
Chicago Patent Group 
U.S. Atomic Energy Commission 
Chicago Operations Office 
9800 South Cass Avenue 
Argonne, Illinois 60439 
Brief 67-10188	 Category 04


Uranyl phthalocyanines show promise in the treatment of brain tumors

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