Technical Aspects and Administration Methods of ¹⁷⁷Lu-DOTATATE for Nuclear Medicine Technologists

Recommended Gravity Infusion Method

The first method of administration, derived from the NETTER-1 clinical study investigator brochure, is the gravity infusion method (3). The expanded-access protocol for therapeutic use of ¹⁷⁷Lu-DOTATATE uses the gravity infusion method as the standard operating procedure to administer the liquid therapy agent. The premise of this method suggests that the flow of saline into the ¹⁷⁷Lu-DOTATATE vial induces pressure, which, in turn, pushes the radiopharmaceutical out of the vial and into the intravenous catheter of the patient. The gravity infusion method calls for an infusion pole, a 250-mL bag containing a 9 mg/mL solution of saline, a long-needle (90–100 mm) gravity intravenous infusion set, a short-needle (3 cm, 18 gauge) gravity intravenous infusion set, and a pair of forceps (3). The ¹⁷⁷Lu-DOTATATE vial is encased in a lead pig. A 250-mL bag of saline is hung, and the tubing is connected to the short needle (3). The short needle is used to puncture the ¹⁷⁷Lu-DOTATATE vial at an angle, with the needle tip sitting in the air pocket at the top of the ¹⁷⁷Lu-DOTATATE vial (3). The short needle is used for the saline drip into the vial (3). Next, the long needle is attached to the intravenous catheter tubing and used to puncture the ¹⁷⁷Lu-DOTATATE vial at an angle, with the needle tip sitting at the bottom of the vial and inside the radiopharmaceutical liquid (3). The long needle is used to transfer the ¹⁷⁷Lu dose into the patient (3). Once the flow of saline begins, the radiopharmaceutical is pushed into the intravenous catheter of the patient (3). The flow of saline is controlled by a pump at a rate of 50–100 mL/h for 10 min and then is increased to 200–300 mL/h for an additional 30 min (3).

Challenges of the Gravity Infusion Method

There were several challenges with the gravity infusion method. First, it was difficult to assess how much of the radiopharmaceutical was administered over time. The amount of dose infused over time was important at our facility as there were occasions on which our radiologist chose to infuse only a portion of the 7.4-GBq (200-mCi) dose because of abnormal bloodwork results or toxicity. In theory, the amount of saline administered should directly relate to the amount of radiopharmaceutical administered. However, in our experience, this was not the case. The time it took to administer each dose varied significantly despite use of the same rate and volume of saline flow for every infusion. The second difficulty of the gravity infusion method was loss of air pressure in the vial, which occurred during 4 of the 37 drug administrations. We found that loss of air pressure could be avoided by stabilizing the needles and puncturing the vial at the outer, thicker, portion of the septum. This technique ensures that the puncture holes of the vial do not become enlarged during infusion, which can cause loss of air pressure. Loss of air pressure, in turn, can result in loss of the air pocket, which can cause the radiopharmaceutical to bubble out of the top of the vial and slow or stop the infusion. To remedy the loss of air pressure, we needed to infuse 5 mL of air into the saline line to recreate an air pocket in the vial. The need to constantly monitor the vial for loss of the air pocket was also exposing the technologist to additional radiation. During 1 infusion, the loss of air pressure prevented us from infusing the dose. In this instance, the only alternative was to draw up and hand-inject the remaining dose. The hand injection rescue method subjected the physician and the surrounding personnel to additional exposure even when shielded.

Possible Solutions to the Challenges

We corrected the issues of the gravity infusion method by placing the ¹⁷⁷Lu-DOTATATE vial (with lead pig) into an acrylic box to prevent exposure from contamination in case the radiopharmaceutical bubbled outside the top of the vial. We also placed a digital pocket dosimeter on top of the acrylic box to measure mR/h and found that the reading was directly related to the dose administered (as the peptide receptor radionuclide therapy decreased in the vial, the mR/h reading decreased). Once these issues were resolved, we found that this method was feasible but still increased the exposure of the technologist, who had to closely monitor the vial throughout the infusion. The gravity infusion method was also difficult to reproduce successfully when attempted by all technologists.

The many challenges of the gravity infusion method and the high radiation exposure of the physician needing to hand-inject the dose after a failed infusion led us to search for a more reliable method. Knowing that ¹⁷⁷Lu-DOTATATE would soon be approved by the Food and Drug Administration and that the demand would increase, we decided to search for a more reliable method of infusion. We developed the infusion pump protocol and successfully implemented it at our facility. This protocol has proven to be reliable and efficient, reducing the exposure of all involved. It is a consistent method of liquid dose infusion with a low possibility for contamination or error.

Alternate Method of Administration, the Infusion Pump Protocol

The infusion pump protocol uses any commercially available infusion pump, a male-to-male adaptor, a 3-way stopcock, infusion pump tubing, an 18-gauge (3.5-in) spinal needle, a micron filter, an 18-gauge (1.5-in vent needle), forceps, and a 10-mL saline vial (Fig. 1). The logic behind the infusion pump protocol is simple. The infusion pump pulls the liquid therapy out of the vial via an 18-gauge spinal needle and infuses it into the patient. First, the ¹⁷⁷Lu-DOTATATE vial is ventilated with a micron filter (Fig. 2). Then, the infusion pump tubing is primed and inserted into the pump. The liquid therapy is infused at a rate of 0.8 mL/min for 30 min. At the end of infusion, 10 mL of saline are injected into the ¹⁷⁷Lu-DOTATATE vial through the micron filter and the pump is set to an infusion rate of 2 mL/min for 5 min (Figs. 3 and 4). The 5-min saline infusion is used to rinse the vial of any residual dose.

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FIGURE 1.

Materials for pump protocol. Moog pump is shown on left and injection supplies on right.

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FIGURE 2.

Vent needle set-up.

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FIGURE 3.

¹⁷⁷Lu-DOTATATE patient set-up using pump protocol.

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FIGURE 4.

Room set-up for pump protocol.

Challenges to the Infusion Pump Protocol

The recommended standard operating procedure for ¹⁷⁷Lu-DOTATATE administration requires the dose to be diluted with 250 mL of saline solution throughout a 30-min infusion. This was the first major challenge of the infusion pump protocol. The recommended saline dilution was not possible with the infusion pump protocol we developed. For this reason, we needed approval from our radiologist and physicians to alter the standard operating procedure and remove the need for saline dilution during infusion of the liquid therapy. Another minor hurdle of this method was the need to allot extra time for set-up of the equipment before administration. Equipment set-up typically takes an additional 10 min. The final challenge of this method was the extra cost of an infusion pump. However, the need for a more efficient, reliable, and predictable method of administering ¹⁷⁷Lu-DOTATATE justified the cost of the equipment. The decreased chance of contamination and radiation exposure of the staff alone made the purchase worthwhile.