Hospital Radiopharmacy Research Articles

Preparation of Patient Doses of 177Lu-DOTA-TATE Using Indigenously Produced 177Lu: The Indian Experience

(177)Lu (T(1/2) = 6.73 days, E(β(max)) = 0.497 MeV, E(γ) = 113 KeV [6.4%] and 208 KeV [11%])-labeled DOTA-TATE, a somatostatin analog, is presently being considered a promising agent for the treatment of patients suffering from inoperable neuroendocrine tumors, which overexpress somatostatin receptors. The objective of the present work was to develop an optimized protocol for the preparation of therapeutic dose of (177)Lu-DOTA-TATE with as high as achievable specific activity at the time of its administration, taking into account the variable specific activity of (177)Lu available during the preparation of the agent. (177)Lu labeling of DOTA-TATE was carried out using a precalculated amount of DOTA-TATE based on the available specific activity of (177)Lu at the time of preparation, keeping a minimum molar ratio of [DOTA-TATE]:[Lu] = 4:1, so that (177)Lu-DOTA-TATE could be obtained with highest possible specific activity without compromising its radiochemical purity and stability. One hundred (100) batches of (177)Lu-DOTA-TATE were prepared following this protocol till date at five different nuclear medicine centers of India, with a radiochemical purity of 98.25% ± 1.1% and specific activity of 32.74-65.49 GBq/μmol (885-1770 mCi/μmol). Till date, 250 patient doses of (177)Lu-DOTA-TATE have been dispensed and administered in 150 patients suffering from various types of neuroendocrine-originated tumors. The developed method ensures that patient doses of (177)Lu-DOTA-TATE could be prepared with highest possible specific activity depending upon the available specific activity of (177)Lu at the hospital radio-pharmacy.

A novel electrochemical 99Mo/99mTc generator

A novel electrochemical process to avail clinical grade 99mTc from (n,γ)99Mo has been demonstrated. The electrochemical parameters were optimized to maximize the 99mTc yield with minimal 99Mo contamination. 99Mo/99mTc generators containing up to 29.6 GBq (800 mCi) 99Mo were developed and their performance were extensively evaluated for 10 days without changing the operating conditions. Very high radioactive concentration of 99mTcO4− of acceptable quality, commensurate with hospital radiopharmacy requirements could be availed from the system with >90% yield. The compatibility of the product for the formulation of 99mTc labeled radiopharmaceuticals such as 99mTc-DMSA and 99mTc-EC was found to be satisfactory in terms of high labeling yields. The proposed route represents an important step for enhancing the scope of accessing clinical grade 99mTc from low specific activity (n, γ)99Mo.

A simple and rapid technique for recovery of 99mTc from low specific activity (n,γ) 99Mo based on solvent extraction and column chromatography

A simple and inexpensive method of separation of 99mTc from 99Mo produced by neutron activation of 98Mo via the 98Mo(n,γ) 99Mo nuclear reaction is described. The recovery of 99mTc was performed by solvent extraction technique followed by column (active alumina) chromatography. The overall radiochemical yield for the complete separation of 99mTc was 85–95% ( n=10). The separated Na[ 99mTc]TcO 4 was of high radionuclidic, radiochemical, and chemical purities. The method can be adopted for routine use of 99mTc in hospital radio-pharmacies utilizing low-medium specific activity (n,γ) 99Mo produced in a research reactor.

How to combine hygiene and radiation protection for radiopharmaceuticals preparation? Analysis in France and propositions

Radiopharmaceuticals for intravenous administration are considered as sterile medicinal products. Their preparation in hospitals involves adherence to regulations on radiation protection as well as to sterility requirements for parenteral administration. These two basic aspects are often opposite, making the working conditions difficult to define. Official texts that have included hygiene and radiation protection do not precisely state how to combine these two aspects in practice. Thus, after an analysis of the bibliography available, this review will show that even if hospital radiopharmacy departments in France are not able to work in total aseptic environments, some measures can be taken in order to improve preparation conditions.

A multi-centre study of dispensing methods and hand doses in UK hospital radiopharmacies

Methodologies for dispensing radiopharmaceuticals have been studied in six UK radiopharmacies. The aims of the study were to compare the dose per unit activity handled using the different dispensing techniques, determine the main factors influencing the dose, and identify the area of the hand likely to receive the highest exposure. Finger doses were measured using an electronic finger dosemeter while dispensing procedures were observed. Three different techniques were used to withdraw radioactivity from a vial, involving a fully inverted vial, a non-inverted vial angled at 45 degrees, and a V technique in which vial and syringe are tilted at small angles in opposite directions. Provided the operators are skilled in carrying out the manipulations, the most important factor affecting the radiation doses to the hands is the extent to which syringe shields are deployed. However, the influence of technique on the dose to the dominant hand was much less than that from use of a syringe shield, although the technique involving an inverted vial gave a greater dose to the non-dominant hand. Results suggest that the tip of the index finger is likely to receive the highest dose and this position is recommended for routine dose monitoring.

99mTc gel generators based on zirconium molybdate-99Mo: III: Influence of preparatory conditions of zirconium molybdate-99Mo gel on generator performance

AbstractThe effect of subtle variations on zirconium molybdate-99Mo gel preparatory conditions, such as stoichiometry of reactants, pH of gel formation, conditioning of gel granulesetc., prior to elution were investigated primarily to arrive at the conditions resulting in high99mTc release and minimal99Mo breakthrough upon elution with normal saline. Zirconium molybdate-99Mo gels were prepared by reacting solutions of Zr and Mo in mole ratios of 0.75-1.5. Both water and normal saline were used for gel disintegration, and the release of99mTc and99Mo from gel columns into eluates was compared. Sharper elution profile of99mTc, but with significantly higher99Mo breakthrough (5-8 times), was obtained when water alone was used for disintegration and elution, in comparison to when saline was used.Gels exhibiting optimum characteristics were found to be formed at a pH of 4-5 by reacting [Zr]:[Mo] in the mole ratio of 1.25:1 and after drying, the product was dispersed into granules by disintegration with normal saline.99mTc elution efficiency was found to be ∼75% and99Mo breakthrough ∼0.05%. The elution profile was sharp when a 6 g gel column coupled to a 2 g acidic alumina column (to trap99Mo) was eluted with 6-9 ml normal saline. Generators containing upto 23 GBq99Mo were prepared, eluted extensively without changing the alumina column and found to provide pertechnetate of good quality, commensurate with hospital radiopharmacy requirements.

99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats

Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S hUV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.

Purification and stabilization of 99mTc-d,l-HMPAO: role of organic extractants

99mTc-d,l-HMPAO, an important SPECT agent for imaging cerebral perfusion, suffers from the disadvantage of an inherent instability and its shelf life has been reported to be 30 min. The latter is a harsh constraint and not compatible with Centralized Radiopharmacy procedures. During the attempts to improve upon the stability of 99mTc-d,l-HMPAO, preservation of product as an organic extract into suitable solvents like diethylether, ethylacetate, methylethylketone, chloroform was tried out. Chloroform extraction (yield: >90%) resulted in a product having stability not less than 5 hours. Gentle drying of the chloroform extract and reconstitution in normal saline resulted in quantitative recovery of 99mTc-d,l-HMPAO with acceptable radiochemical purity (>90%). This finding is thus of much significance, especially in the context of centralized large hospital radiopharmacy setting, by rendering convenience and flexibility in scheduling patients.

Book reviews

This small booklet of less than 50 pages packs in a great deal of useful information and advice about modern hospital radiopharmacy work. It is an update of the Hospital Physicists' Association Report No. 16, The Hospital Preparation of Radiopharmaceuticals. The introduction usefully summarizes the legislative framework, regulations and various guidance notes which are relevant in the radiopharmacy, both from the pharmaceutical point of view and from that of radiation protection.

In-house production and control of a few 99 mTc-radiopharmaceuticals

The methodology adopted for the in-house preparation of seven types of “kits” used in the formulation of 99 m Tc-radiopharmaceuticals, viz. reticuloendothelial, hepatobiliary, renal, skeletal and blood-pool agents, and their control is described. The quality control was performed primarily by following pharmacokinetic patterns (both early vascular “dynamic” and late “static” phases) of the respective radiopharmaceuticals in Wistar strain rats subsequent to i.v. administration of the radiopharmaceuticals. The results obtained could be utilized for quality assurance of 99 m Tc-radiopharmaceuticals; especially those prepared in-house (from “kits”) and used in diagnostic nuclear medicine. The in-house preparation of these “kits” in hospital radiopharmacy laboratories possessing adequate manufacturing facilities, skills and expertise could result in considerable savings in costs (of kits).

Radiobiologic /tissue/ profiles of99mTc-diagnostics: behaviour of99mTc-N/p-butylphenylcarbamoylmethyl/iminodiacetic acid, /99mTc-p-butyl HIDA/, in normal rats

The biologic profiles of a hepatobiliary radiodiagnostic agent,99mTc-N/p-butylphenylcarbamoylmethyl/iminodiacetic acid,99mTc-p-butyl HIDA for short, are described in terms of its pharmacokinetics in normal rats over a 24 h period. It could be used to monitor the quality of this hepatobiliary radiopharmaceutical if prepared in an in-house hospital radiopharmacy.

Hospital radiopharmacy training program

Training of radiopharmacists, including self-study and a hospital short-term course, is discussed. A systematic approach for self-study is suggested. The 30-day hospital training program described includes both didactic material and on-the-job experience.