Preparation of high specific activity technetium-96

The present invention relates to a method of producing Tc-96 from the proton irradiation of a rhodium target and a technique for isolating under remote hot cell conditions the Tc-96 from the proton irradiated target.

BACKGROUND OF THE INVENTION 
Technetium-99m is the most widely used radiotracer in nuclear medicine. A 
rare combination of nuclear properties gives this radionuclide 
considerable advantages over other agents in diagnostic applications such 
as organ visualization and tumor localization. The development of a simple 
generator, over a decade ago, to elute Tc-99m from its parent makes it 
possible to use the isotope at great distances from the production site. 
Technetium-99m is a useful tracer in nuclear medicine because of its short 
half-life (6 hours) and its gamma radiation energy (140 KeV) which has 
satisfactory tissue penetration and is easily collimated. The absence of 
beta radiation makes feasible the administration of millicurie amounts of 
Tc-99m with tolerable radiation dose to the patient. 
However, the six hour half-life of Tc-99m makes it impossible to conduct 
chemical, in-vitro, and animal studies with Tc-99m labeled diagnostic 
agents that require a longer study period. Because Tc-99m is the most 
important isotope in nuclear medicine, it is often advantageous to be able 
to conduct such long term studies and thus it would be advantageous to 
have a stand-in for Tc-99m that possessed a much longer half-life. It is 
known that Tc-96 has the desired longer half-life (4.35 days) while 
retaining the useful nuclear properties of Tc-99m. However, the previous 
methods of preparing Tc-96, the Nb(.sup..alpha.,n) reaction [Edwards, et 
al., Phys. Rev., 72, 384 (1947)], the .sup.96 Mo(p,n) reaction [Monaro, et 
al., Can. J. Phys., 46, 2375 (1968)], and the .sup.96 Mo(d,2n) reaction 
[Cesareo, et al., Zeit. Phys., 205, 174 (1967)] fail to produce the 
isotope in usable quantity and failed to produce material of the high 
specific activity needed for biomedical applications. 
It is thus an object of the present invention to provide a process for 
preparing high specific activity Tc-96 useful in biomedical applications. 
It is a further object of the present invention to provide a technique for 
preparing and purifying Tc-96 in quantities useful for nuclear medicine.

DETAILED DESCRIPTION OF THE INVENTION 
The present invention relates to a method of preparing high specific 
activity Tc-96 useful for biomedical applications. Technetium-96 decays by 
electron capture with a 4.35 day half-life. It has easily detectable gamma 
ray emissions with its major emissions as follows: 
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Auger Electrons 14.8 KeV (20%) 
2.3 KeV (95%) 
Photons 17.4 KeV (54.8%) 
778.2 KeV (99.8%) 
812.5 KeV (82%) 
849.9 KeV (98%) 
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The 4.35 day half-life and the gamma ray emissions make Tc-96 useful as a 
substitute for Tc-99m in chemical, in-vitro or animal studies with 
technetium labeled agents carried beyond the useful life of Tc-99m. The 
labeling techniques used traditionally for Tc-99m are equally appropriate 
for Tc-96. Technetium-96 is a useful substitute because while a Tc-96 
labeled agent will exhibit the same pattern of distribution and same 
physiological behavior as the comparable Tc-99m labeled material, the 
useful half-life of the radiolabel is extended from 6 hours to over 4 days 
to permit extended studies. 
According to the present invention, Tc-96 is produced and isolated from a 
high purity rhodium target using the .sup.103 Rh(p,3p5n)Tc96 reaction. 
This approach to the production of Tc-96 is attractive because proton 
irradiation of the rhodium target results in two useful radionuclides, 
Tc-96 and Ru-97. The rhodium target is irradiated with protons at energy 
levels between approximately 70 MeV and 160 MeV at the Brookhaven Linac 
Isotope Production facility ("BLIP") at Brookhaven National Laboratory. 
The following examples illustrate the method of the present invention. 
EXAMPLE 1 
Irradiation of Rhodium Target and Isolation of Technetium-96 
A high purity rhodium target foil, 0.025 cm thick and measuring 
2.5.times.2.5 cm in area, is clipped onto a stainless steel backing plate 
for insertion into a BLIP target holder, placed in a water gap between 
larger disk targets. The target is irradiated at 90 MeV for several days. 
After bombardment, the target is transferred to a processing hot cell and 
dissolved by a.c. electrolysis in a small cell made of glass. The Rh foil 
is used as one of the electrodes, a graphite rod the other electrode, and 
the electrolyte is 6N HCl. The Rh foil is held by a clamp consisting of 
two graphite rods with a small graphite disk (acting as a fulcrum) between 
them. A rubber "O" ring placed below the disk supplies tension to hold the 
Rh between the ends of the graphite rods. In this manner the entire Rh 
foil can be immersed in the electrolyte. Also, to obtain high current 
density and even surface electrical fields, the other graphite rod 
electrode is encased to within about 1 cm of the bottom with shrink 
tubing. Current densities of 0.3 A/cm.sup.2 dissolve the target (99% 
dissolution) in 12-15 hours. 
The resulting solution is sucked by vacuum into a flask where it is 
evaporated to near dryness to remove the HCl and 3 ml of water are added. 
The solution is transferred by pressure to a distillation flask to which 
is added an oxidizing mixture of 3 ml of 12N H.sub.2 SO.sub.4 and 3 ml of 
KMnO.sub.4. Ruthenium-97 is distilled as .sup.97 RuO.sub.4 which is 
collected in a vessel containing 1:1 HCl:EtOH to give a solution 
containing predominantly ruthenium (III) chloride. The overall Ru-97 
recovery is about 90%. 
To separate the technetium, the rhodium sulfate residue is transferred to a 
separatory funnel and 11N NaOH added to make the solution strongly basic. 
Some Rh salt precipitates at this point, but it does not carry the Tc 
which remains in solution. Filtration to remove the precipitate is not 
essential but does aid in subsequent remote solution transfer and in 
visualization of the phase boundary during solvent extraction. Technetium 
is separated nearly quantitatively by repeated extractions with distilled 
methyl ethyl ketone, using bubbled N.sub.2 to mix the phases. The organic 
phase is evaporated and the Tc-96 recovered in 0.05N NH.sub.4 OH in the 
form of ammonium pertechnetate. With two extractions in methyl ethyl 
ketone, the overall Tc-96 recovery was 95%. The apparatus to perform these 
separations remotely in a hot cell is shown schematically in FIG. 1. If it 
is not desired to produce Ru-97 as well as Tc-96 from the irradiation of 
the rhodium target, the distillation step can be eliminated so that the 
isolation procedure leads directly to the Tc-96. 
The final product contains only .sup.95,.sup.95m,.sup.96 Tc. The 
preliminary yield of Tc-96 from a 0.025 cm thick target was 1.8 mCi/.mu.A 
at end of bombardment (EOB). After correcting for the fraction of the beam 
actually hitting the Rh target, a production rate of 12.0 mCi/.mu.A is 
obtained even in this relatively thin target. 
Although the small area target gives adequate quantity of Ru-97, a larger, 
thicker target can be used to produce more Tc-96. After a 4 day irradition 
at approximately 90 MeV the ratios .sup.95 Tc/.sup.96 Tc and .sup.95m 
Tc/.sup.96 Tc were 3.9 and 2.3.times.10.sup.-2 respectively at EOB. After 
processing and shipment the .sup.95 Tc/96Tc ratio declines to 0.5. This 
ratio can be controlled by adjusting the proton energy, the length of 
irradiation and the decay time after EOB, even though Tc-95 does not 
interfere in tracer applications of Tc-96. Technetium-96 as ammonium 
pertechnetate is appropriate for use in biomedical applications. 
EXAMPLE 2 
Nuclear Yield and Radiopurity 
The target irradiation was repeated as in Example 1 using a thin target 
(0.025 cm) with an irradiation at 160 MeV. 
The preliminary yield of Tc-96 at 160 MeV was 130 .mu.Ci/.mu.Ah in the thin 
target. The radiopurity ratios from two test irradiations are shown in 
Table 1. It is clear that at end of bombardment substantial quantity of 
short lived Tc-95 is produced. This impurity can be better controlled 
because the relative amount of Tc-95 decreases as the beam energy 
decreases and as the irradiation duration increases. Relative to Tc-96, 
only very small amounts of longer lived Tc-95m are produced. The presence 
of Tc-95 does not interfere with tracer applications of Tc-96. 
TABLE 2 
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Ratio of .sup.95, 95m Tc to .sup.96 Tc 
A(.sup.95 Tc)/A(.sup.96 Tc) 
A(.sup.95m Tc)/A(.sup.96 Tc) 
E(MeV) T.sub.irr (H) 
EOB 72 h* EOB 72 h 
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90 89.7** 3.9 0.52 2.3 .times. 10.sup.-2 
3.6 .times. 10.sup.-2 
160 71.5 5.3 0.71 1.3 .times. 10.sup.-2 
2.0 .times. 10.sup.-2 
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*Estimated earliest time of use. 
**Irradiation interrupted for 5.75 h.