Position paper to facilitate patient access to radiopharmaceuticals: considerations for a suitable pharmaceutical regulatory framework.

BACKGROUND: Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals. MAIN BODY: This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These include the distinct characteristics of radiopharmaceuticals which require dedicated regulations, considering the impact of the variable complexity of radiopharmaceutical preparation, personnel requirements, manufacturing practices and quality assurance, regulatory authority interfaces, communication and training, as well as marketing authorisation procedures to ensure availability of radiopharmaceuticals. Finally, domestic and regional supply to ensure patient access via alternative regulatory pathways, including in-house production of radiopharmaceuticals, is described, and an outlook on regulatory challenges faced by new developments, such as the use of alpha emitters, is provided. CONCLUSIONS: All these considerations are an outcome of a dedicated Technical Meeting organised by the IAEA in 2023 and represent the views and opinions of experts in the field, not those of any regulatory authorities.

Compelling Case for Fostering Titanium-45 for Positron Emission Tomography Tracer Applications.

The growth of diagnostic nuclear medicine is substantially based on the development, availability, and regular clinical use of cyclotron-based positron emission tomography (PET) tracers. Apart from 18F (110 min) products, the radiometal 68Ga isotope (68 min) has found an increasingly wide clinical acceptance. There is hence much merit in identifying and fostering other radiometal positron emitters, of preferably longer half-life. Titanium-45 (3.08 h) fits the bill well in this context, as it is easy to produce using natural scandium metal target and Ep of 13-14 MeV for 45Sc(p, n) 45Ti reaction. This Commentary cites a compelling case to foster the development of 45Ti products for PET imaging.

Impact of Nuclear Medicine and Radiopharmaceuticals on Health-care Delivery: Advances, Lessons, and Need for an Objective Value-matrix.

The nuclear medicine (NM) growth has gone through both evolutionary and revolutionary changes over decades, mostly attributable to the dynamic and responsive trends in the global development and deployment of radiopharmaceuticals (RPh), as well as the advent of superior technology imaging systems (single-photon emission computed tomography/computed tomography [CT], positron emission tomography [PET]/CT, PET/magnetic resonance) with quantification capability. There are naturally many crucial lessons learnt along the way of NM-RPh progress achieved. It is felt imperative for the NM-RPh community to have consensus-based list(s) of indications for NM, classified on the value-level basis, at NM gross-level and specific medical specialty-wise, and the corresponding RPh needed, to ensure harmonious communication with the referral medical fraternity and health-care policymakers. For this purpose, a "NM value-matrix" is proposed in terms of "NM utility grading" (unique value, significant value, useful value, and others) versus "patient volume" (i.e., large, medium, low, and rare cases), covering the established and emerging indications for NM procedure, and the corresponding RPh product(s) in use. A consensus-based NM Value-Matrix will portray in an unequivocal manner, the merits of NM-RPh options (also limitations, if any) for serving needy patients.

Evaluation of two methods for concentrating perrhenate (188 Re) eluates obtained from 188 W-188 Re generator.

Two novel and simple methods for post-elution concentration (PEC) of (188)Re-perrhenate, using (i) a single diethyl amino ethyl (DEAE) cellulose anion exchanger column and (ii) a combination of Dowex-1 x 8 and AgCl columns, are described here. In the first system, 20-25 ml of (188)Re-perrhenate in acidic ammonium acetate was trapped in the small anion exchanger column of DEAE cellulose which was subsequently recovered in 4 ml of normal saline. In the second method, (188)Re-perrhenate eluate in 20-40 ml normal saline was trapped on a small strong base anion exchanger column, Dowex-1 x 8, and recovered in 5 ml of 0.2M NaI solution and finally processed over 1g AgCl column so as to obtain it in physiological saline solution in a final volume of 6.5 ml including 1.5 ml de-ionized water washings. In both the methods, the radiochemical purity of (188)Re-perrhenate was >98% and (188)W breakthrough was less than 10(-3)%.

99mTc(CO)3-VIP analogues: preparation and evaluation as tumor imaging agent.

Vasoactive intestinal peptide (VIP) receptors are expressed abundantly on many types of tumors and, hence, radiolabeled VIP analogues are being explored for tumor imaging and therapy. Here, we report synthesis of three VIP analogues and their radiolabeling with (99m)Tc via a novel tricarbonyl synthon. The radiolabeled product could be prepared in high yields (>95%) and stability. In vitro studies showed significant uptake of (99m)Tc(CO)((3))-VP05 in human colon carcinoma cells. Biodistribution studies in animal tumor model showed 0.4-1%ID/g tumor uptake.

99mTc carbonyl t-butyl isonitrile: a potential new agent for myocardial perfusion imaging.

OBJECTIVE: The recent development of mixed ligand complexes using a 99mTc tricarbonyl synthon has prompted us to revisit the first generation product, 99mTc-t-butyl isonitrile (TBI), for possible myocardial imaging after modification of the 99mTc core to a mixed ligand core of carbonyl and t-butyl isonitrile. The easy availability of TBI from commercial sources and the recent promising development of a 'kit' procedure to prepare the 99mTc tricarbonyl aqua synthon/precursor [99mTc(H2O)3(CO)3]+ were other factors that triggered this work. METHODS: The carbonyl precursor (37-370 MBq/0.5 ml) was synthesized and reacted with TBI (3 mg.ml-1) at room temperature and at pH 8 for 1 h. [99mTc(CO)3(TBI)3]+ was characterized by C18 reverse phase HPLC in gradient mode with water and acetonitrile as solvent. Biodistribution studies were carried out in normal mice and planar images were acquired in rabbit at 5 min, 30 min, 1 h, 2 h and 4 h post-injection to assess heart uptake and soft tissue retention. [99mTc(CO)3(TBI)3]+was formed as a single species in >95% yield and was found to be stable. Biodistribution studies in mice revealed 2.3 (+/-0.2)% uptake in heart at 5 min p.i. with heart/liver, heart/lung and heart/blood ratios of 1.5, 2.0 and 30, respectively. Imaging studies in rabbits showed high uptake in myocardium, with negligible activity in blood and lungs, at 5 min p.i. that washed out of the heart after 4 h. CONCLUSION: [99mTc(CO)3(TBI)3]+ could be prepared in >95% yields. The complex showed high myocardial uptake with desirable rate of washout from heart in rabbits. [99mTc(CO)3(TBI)3]+ has potential to extend to larger animal studies and later for clinical evaluation as a myocardial imaging agent.