System for generating and containerizing radioisotopes

A system for eluting a daughter radioisotope from a parent radioisotope and containerizing the resultant eluate in an evacuated container having a rubber stopper, providing for delivery of eluant from a reservoir through a charge of the parent radioisotope in a generator and thence to a tubular needle adapted to be pierced through the stopper of the evacuated container for suctioning the eluant from the sealed eluant supply into the generator and for suctioning the resultant eluate into the container. The needle is at the lower end of a valve body having a valve plug rotatable therein between a closed and open position. The plug is adapted to be pushed down to push the valve body down to cause the needle to pierce the stopper, after which the plug is rotated to open position, in which it effects venting of the eluant reservoir to atmosphere, delivery of eluant from the reservoir to the generator, and delivery of eluate from the generator to the needle.

BACKGROUND OF THE INVENTION 
This invention relates to a system for generating and containerizing 
radioisotopes, and more particularly to apparatus for the generation and 
containerization under sterile conditions of radioactive isotope solutions 
such as are obtained as the eluate in a radioisotope generator system. 
Reference may be made to the coassigned U.S. Pat. No. 3,655,981, issued 
Apr. 11, 1972, entitled Closed System Generation and Containerization of 
Radioisotopes for Eluting a Daughter Radioisotope from a Parent 
Radioisotope, disclosing a system for the preparation and packaging, under 
sterile conditions, of a solution of a daughter radioisotope, such as 
technetium-99M, generated from a parent radioisotope, such as 
molybdenum-99, wherein the daughter radioisotope is eluted from a parent 
radioisotope contained in a generator with an anion exchange medium or 
other medium, such as alumina, having a high adsorptive capacity for the 
parent but a low adsorptive capacity for the daughter, by washing with a 
suitable solvent or eluant such as a sterile, pyrogen-free isotonic saline 
solution. The present invention involves improvements over the prior 
system. 
SUMMARY OF THE INVENTION 
Among the several objects of this invention may be noted the provision of 
an improved system for generating and containerizing radioisotopes which, 
while enabling use of a reservoir for the eluant with an air vent for 
atmospheric pressurization of the eluant in the reservoir for delivery of 
the eluant from the reservoir, inhibits leakage of eluant from the 
generator of the system; the provision of such a system for generating and 
containerizing radioisotopes under sterile conditions; and the provision 
of such a system which is easy to use. 
In general, the system of this invention, which is operable for eluting a 
daughter radioisotope from a parent radioisotope and for containerizing 
the resultant eluate in an evacuated container having a closure adapted to 
be pierced by a needle, comprises a generator containing a supply of the 
parent radioisotope, the generator having an inlet for an eluant for 
eluting the daughter radioisotope from the parent radioisotope and an 
outlet for the resultant eluate, a reservoir for holding a supply of the 
eluant, the reservoir having an outlet for delivery of eluant to the inlet 
of the generator and an air inlet for admission to the reservoir of air 
from the atmosphere to apply atmospheric air pressure to eluant in the 
reservoir, a tubular needle for piercing the closure of an evacuated 
container, and valve means comprising a first port constituting an air 
inlet in communication with the atmosphere, a second port in communication 
with said reservoir air inlet, a third port interconnected with said 
reservoir outlet, a fourth port interconnected with said generator inlet, 
a fifth port interconnected with said generator outlet for delivery of 
eluate to the needle, and means for blocking communication between said 
first and second ports, between said third and fourth ports, and between 
said fifth port and the needle, and operable to place the first port in 
communication with the second, the third in communication with the fourth 
and the fifth in communication with the needle. 
Other objects and features will be in part apparent and in part pointed out 
hereinafter.

Corresponding reference characters indicate corresponding parts throughout 
the several views of the drawings. 
DESCRIPTION OF THE PREFERRED EMBODIMENT 
Referring to the drawings, first more particularly to FIG. 1, a system of 
this invention for generating and containerizing radioisotopes is shown to 
comprise a generator 1 containing a sterile pyrogen-free supply 3 of a 
parent isotope. Generally, this generator comprises an elongate cylindric 
glass tube having pierceable closures 5 and 7 at its upper and lower ends 
(upper and lower as shown in FIG. 1) each constituted by a rubber stopper 
plugged in the respective end of the container. An aluminum foil cover 9 
is shown for each stopper with a central circular section of the cover 
removed. The parent radioisotope may be molybdenum-99, for example, 
adsorbed on an anion exchange medium, alumina or other medium (as in U.S. 
Pat. No. 3,655,981) for generating technetium-99M. The generator could be 
a tin/indium or germanium/gallium generator. Pierced through the rubber 
stopper at the upper end of the generator is the downturned end 11 of a 
relatively thin metal tube 13 constituting an eluant inlet for the 
generator. Pierced through the rubber stopper at the lower end of the 
generator is the upturned end 15 of a relatively thin metal tube 17 
constituting an eluant outlet for the generator. 
At 19 is shown a reservoir for holding a supply of eluant 21 (e.g., saline 
solution). Preferably, this is a glass bottle having a rubber stopper 23 
in its mouth with an aluminum foil cover 25 for the stopper, shown in FIG. 
1 with a central circular section of the cover removed. Pierced through 
the stopper 23 is the downturned end 27 of a relatively thin metal tube 29 
constituting an air inlet for the reservoir or bottle, for admission of 
air to the bottle to apply atmospheric air pressure on the eluant 21 in 
the bottle. Also pierced through the stopper 23 is the downturned leg 31 
of a thin metal tube 33 constituting an eluant outlet for the bottle. The 
downturned leg 31 of the tube 33 extends down in the bottle nearly to the 
bottom of the bottle for the delivery of eluant upwardly through the leg 
31. 
At 35 is indicated a valve means comprising a valve body 37 carrying a 
tubular needle 39 for piercing the rubber stopper 41 of a sealed sterile 
evacuated container or vial 43, shown in FIG. 1 as having an aluminum foil 
cover 45 from which a removable circular central section has been removed 
leaving an opening in the cover. Means indicated generally at 47, which 
may comprise part of a case corresponding generally to the case shown in 
U.S. Pat. No. 3,655,981, mounts the valve body for movement downwardly 
from its raised retracted position of FIGS. 1 and 2, for causing the 
needle to pierce the rubber stopper or closure 41 of the evacuated 
container 43, and for movement back up to its raised retracted position. 
The means 47 comprises an overhanging portion of the case, having top and 
bottom walls 49 and 51 and an outer wall 53. 
The valve body has an upper section 55 and a lower section 57 extending 
down from the upper section. The upper section is formed to provide a 
cylindrical recess 59 extending down from its upper end, and the lower 
section is formed to provide a passage 61 of smaller circular cross 
section than the circular cross section of recess 59 extending down from 
the bottom of the recess to the lower end of the lower section. The 
passage 61 is enlarged at its lower end as indicated at 63 for reception 
of an enlarged head 65 at the upper end of the needle 39. At 67 is 
indicated a valve member having a lower cylindrical section 69 
constituting a valve plug having a rotary sealing fit in the recess 59, 
and an enlarged upper section or plug extension 71, the lower end of the 
latter engaging the upper end of the valve body. Extension 71 of the plug 
69 is vertically slidable in an opening 73 in the top wall 49 of the 
overhang 47, and section 57 of the valve body is vertically slidable in an 
opening 75 in the bottom wall 51 of the overhang. Section 55 of the valve 
body has a pair of ribs 77 slidable between lugs 78 on the inside of wall 
53 (see particularly FIG. 6) to guide the valve body and hold it against 
rotation on its vertical axis. A spring 79 biases the valve body (and 
plug) upwardly to their raised retracted position of FIGS. 1 and 2, which 
is determined by engagement of the upper end of the valve body with first 
and second stops 80 and 81 on the bottom of wall 49. The plug extension 71 
has a knob 82 keyed to it at its upper end for turning it. 
The upper section 55 of the valve body has a vertical series of five ports 
therein extending between the cylindrical recess 59 and the side of the 
body opposite the wall 53, these ports being designated P1-P5 from the top 
down. The upper or first port P1 constitutes an air inlet in communication 
with the atmosphere, having a bacteriological filter 83 therein for 
precluding entry of bacteria to the recess 59 in the valve body and thus 
maintaining sterile conditions in the valve body. The second port P2 from 
the top is in communication with the air inlet tube 29 for the reservoir 
or bottle 19 via a flexible plastic tube 85. The third port P3 is 
interconnected with the outlet tube 33 for the reservoir or bottle 19 via 
a flexible plastic tube 87. The fourth port P4 is interconnected with the 
generator inlet tube 13 via a flexible plastic tube 89. The fifth (bottom) 
port P5 is interconnected with the generator outlet tube 17 via a flexible 
plastic tube 91 for delivery of eluate to the needle 39. The flexible 
plastic tubes permit the up and down movement of the valve body. 
The valve plug 69 is rotatable in the recess 59 of the valve body between a 
first or closed position (FIGS. 1-3, 5 and 6) wherein it blocks 
communication between the first and second ports P1 and P2, between the 
third and fourth ports P3 and P4, and between the fifth port P5 and the 
needle, and a second or open position (FIG. 4) for communication between 
the first and second ports P1 and P2, between the third and fourth ports 
P3 and P4, and between the fifth port P5 and the tubular needle 39. For 
this purpose, the plug has a first groove 93 for communication between the 
ports P1 and P2, a second groove 95 for communication between P3 and P4, 
and a third groove 97 for communication between P5 and the upper end of 
passage 61, when the plug is turned to its said second or open position. 
These grooves are located in a radial plane of the plug; this plane comes 
into the vertical plane of the ports P1-P5 when the plug is rotated to its 
open position. The plug extension 71 has a key 99 slidable in notch 101 
which extends radially outwardly from the opening 73 in the top wall 49 of 
the overhang. This key prevents rotation of the plug away from its closed 
position until the knob 81 is pushed down to push down the plug and the 
valve body to a lowermost position wherein the upper end of the key is 
below the top wall 49 (see FIGS. 3 and 4). This frees the plug 69 for 
rotation to its open position. Before the spring 79 can raise the valve 
body and plug back up to their raised retracted position, the plug must be 
turned back to its closed position (aligning the key 99 with the notch 
101). 
The various components of the system are all sterilized before assembly, 
and assembled under sterile conditions. The valve means 35 is such that it 
may be readily sterilized. The generator 1, containing the sterile 
pyrogen-free supply 3 of the parent radioisotope, is placed in a lead 
shield indicated in phantom at 103 in FIG. 1. The bottle is supplied 
sealed with the sterile pyrogen-free eluant (e.g., saline solution) 
therein. 
In the use of the system, an evacuated container or vial 43 held in a lead 
cup (not shown) is placed in position for having the tubular needle 39 
driven down through its stopper 41, and the knob 82 is then pushed down to 
drive the valve plug 69, valve body 37 and needle 39 down to cause the 
needle to pierce through the stopper of the vial. The knob is pushed down 
all the way to the point where the upper end of the key 99 is below the 
top wall 49 of the overhang 47, thereby permitting the valve plug 69 to be 
turned by turning the knob, and the plug is turned to its open position, 
which is determined by engagement of key 99 with the stated second stop 
81, as indicated in phantom in FIG. 5. The first or closed position of the 
plug is determined by engagement of the key 99 with the first stop 80 as 
shown in solid lines in FIG. 5. With the plug in its open position, groove 
93 interconnects ports P1 and P2, groove 95 interconnects ports P3 and P4, 
and groove 97 interconnects port P5 and passage 61 to the needle 39. With 
ports P1 and p2 interconnected, the eluant in the bottle 19 is subjected 
to atmospheric air pressure via the bacteriological filter 83, port P1, 
groove 93, port P2, and tubes 85 and 29, and with vacuum in the vial 43, 
eluant is caused to flow from the bottle 19 through the outlet tube 33 and 
tube 87 to port P3, thence through groove 95, port P4, and tubes 89 and 13 
to the generator 1 for eluting the daughter radioisotope from the parent 
radioisotope in the generator. The resultant eluate flows from the 
generator through its outlet tube 17 and tube 91 to port P5 and thence 
through groove 97, passage 61 and the tubular needle 39 into the vial 43. 
The plug 69 is maintained in its open position until the desired amount of 
eluate has been suctioned into the vial 43, and is then turned by means of 
knob 82 to closed position and released to be returned along with the 
valve body 37 to their raised retracted position of FIGS. 1 and 2. When 
the plug is turned to closed position, key 99 is aligned with notch 101 to 
allow the plug (and valve body) to move up (see FIG. 5). The key 99 
prevents the valve body and plug from moving upwardly to the raised 
retracted posiition until the plug is turned to closed position. With the 
plug in closed position the valve means 35 positively prevents leakage of 
eluant from the generator 1 by (a) closing off the air vent line 85, 29 to 
the eluant bottle 19, (b) closing off the eluant line 33, 87 from the 
bottle to prevent flow of eluant into the generator, and (c) closing off 
the eluate line 17, 91 from the generator to prevent flow of eluate from 
the generator to the needle 39. 
The valve body 37 and the valve plug 69 of the valve means 35 are 
preferably molded from a plastic which may be sterilized. Polypropylene is 
preferred, but polyethylene or styrene may be used. When properly 
assembled (after sterilization) using aseptic techniques, the valve means 
remains sterile. 
In view of the above, it will be seen that the several objects of the 
invention are achieved and other advantageous results attained. 
As various changes could be made in the above constructions without 
departing from the scope of the invention, it is intended that all matter 
contained in the above description or shown in the accompanying drawings 
shall be interpreted as illustrative and not in a limiting sense.