Synthesis and characterisation of DOTA-kisspeptin-10 as a potential gallium-68/lutetium-177 pan-tumour radiopharmaceutical.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. A gallium-68 labelled kisspeptin-10 (KP10), the minimal biologically active structure, has potential as a pan-tumour radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases.

Visualisation of in vivo protein synthesis during mycobacterial infection through [Ga]Ga-DOTA-puromycin µPET/MRI.

Radiolabelled puromycin analogues will allow the quantification of protein synthesis through nuclear medicine-based imaging. A particularly useful application could be the non-invasive longitudinal visualisation of mycobacterial activity through direct quantification of puromycin binding. This study assesses the value of [Ga]Ga-DOTA-puromycin in the visualisation of mycobacteria through positron emission tomography combined with magnetic resonance imaging (µPET/MRI).

Expanding Role for Gallium-68 PET Imaging in Oncology.

Gallium-68 has gained substantial momentum since 2003 as a versatile radiometal that is extremely useful for application in the development of novel oncology targeting diagnostic radiopharmaceuticals. It is available through both generator produced radioactivity and via cyclotron production methods and can therefore be implemented in either small- or large-scale production facilities. It can also be implemented within different spectrum of infrastructure settings with relative ease.

Can current preclinical strategies for radiopharmaceutical development meet the needs of targeted alpha therapy?

Preclinical studies are essential for effectively evaluating TAT radiopharmaceuticals. Given the current suboptimal supply chain of these radionuclides, animal studies must be refined to produce the most translatable TAT agents with the greatest clinical potential. Vector design is pivotal, emphasizing harmonious physical and biological characteristics among the vector, target, and radionuclide.

Biodosimetry, can it find its way to the nuclear medicine clinic?

Personalised dosimetry based on molecular imaging is a field that has grown exponentially in the last decade due to the increasing success of Radioligand Therapy (RLT). Despite advances in imaging-based 3D dose estimation, the administered dose of a therapeutic radiopharmaceutical for RLT is often non-personalised, with standardised dose regimens administered every 4-6 weeks. Biodosimetry markers, such as chromosomal aberrations, could be used alongside image-based dosimetry as a tool for individualised dose estimation to further understand normal tissue toxicity and refine the administered dose.

Preclinical Research Highlighting Contemporary Targeting Mechanisms of Radiolabelled Compounds for PET Based Infection Imaging.

It is important to constantly monitor developments in the preclinical imaging arena of infection. Firstly, novel radiopharmaceuticals with the correct characteristics must be identified to funnel into the clinic. Secondly, it must be evaluated if enough innovative research is being done and adequate resources are geared towards the development of radiopharmaceuticals that could feed into the Nuclear Medicine Clinic in the near future.

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry.

The β emitter, rhenium-188 (Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (Tc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention.

A decade of ubiquicidin development for PET imaging of infection: A systematic review.

Background: Ubiquicidin is a peptide fragment with selective binding to negatively charged bacterial cell membranes. Besides its earlier labelling with gamma emitting radionuclides, it has been labelled with Positron Emission Tomography (PET) radionuclides in the last decade for imaging infection and distinguishing infectious disease from sterile inflammation. This systematic review aims to evaluate the technology readiness level of PET based ubiquicidin radiopharmaceuticals.

Obstacles and Recommendations for Clinical Translation of Nanoparticle System-Based Targeted Alpha-Particle Therapy.

The rationale for application of nanotechnology in targeted alpha therapy (TAT) is sound. However, the translational strategy requires attention. Formulation of TAT in nanoparticulate drug delivery systems has the potential to resolve many of the issues currently experienced.

A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma.

Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT).

Elucidating the effect of specific surface area on the gastrointestinal absorption of nanostructured calcium through Calcium-45 in vivo radiotracing.

Low dietary calcium intake and absorption may increase the risk of hypocalcaemia disease states. Reducing the particle size of calcium-containing powders and increasing the specific surface area (SSA), may have high oral calcium bioavailability. The absorption of a single dose of different sized calcium carbonate nanoparticles was traced in Sprague-Dawley rats with radioactive calcium-45 (half-life = 162.

The use of HEPES-buffer in the production of gallium-68 radiopharmaceuticals - time to reconsider strict pharmacopoeial limits?

HEPES (4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) is a buffer that is used in the radiolabelling of gallium-68 compounds. The beneficial effects of HEPES on molar activity in bioconjugates have been well described. Current strict regulations on the HEPES content in radiopharmaceuticals limit its use when intended for parenteral administration.

Non-oncological applications of RGD-based single-photon emission tomography and positron emission tomography agents.

Introduction: Non-invasive imaging techniques (especially single-photon emission tomography and positron emission tomography) apply several RGD-based imaging ligands developed during a vast number of preclinical and clinical investigations. The RGD (Arg-Gly-Asp) sequence is a binding moiety for a large selection of adhesive extracellular matrix and cell surface proteins. Since the first identification of this sequence as the shortest sequence required for recognition in fibronectin during the 1980s, fundamental research regarding the molecular mechanisms of integrin action have paved the way for development of several pharmaceuticals and radiopharmaceuticals with clinical applications.

Production of [ Ga]Ga-PSMA: Comparing a manual kit-based method with a module-based automated synthesis approach.

The labeling of peptides with gallium-68 is often initially performed by manual labeling, but with high clinical demand, other alternatives are needed. Cold-kits or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [ Ga]Ga-PSMA-11 production methods.

Modelling in the Development of Novel Radiolabelled Peptide Probes.

This review describes the usefulness of in silico design approaches in the design of new radiopharmaceuticals, especially peptide-based radiotracers (including peptidomimetics). Although not part of the standard arsenal utilized during radiopharmaceutical design, the use of in silico strategies is steadily increasing in the field of radiochemistry as it contributes to a more rational and scientific approach. The development of new peptide-based radiopharmaceuticals as well as a short introduction to suitable computational approaches are provided in this review.

A toxicity profile of the Pheroid® technology in rodents.

The Pheroid® drug delivery system is now on the threshold of progressing into human clinical trials for various patented pharmaceutical applications and a systematic investigation of its toxicological properties and is thus a priority. Colloidal dispersions (nano- and microemulsions) demonstrate the ability to be adapted to accommodate either lipophilic, hydrophilic or amphiphilic drug molecules. The colloidal dispersions investigated during this evaluation has a general size of 200 nm - 2 μm, a zeta-potential of -25 mV and the main ingredient was ethyl esters of essential fatty acids.

Radiopharmaceutical enhancement by drug delivery systems: A review.

Introduction: Drug delivery systems are entities designed to alter the biological behaviour of the pharmaceutical active ingredients that they carry in order to afford more beneficial biodistribution and safety profiles. Many problems currently faced by the field of nuclear medicine (e.g.