Current Radiopharmaceuticals - Volume 18, Issue 4, 2025

Presently, heavy particle ion radiation therapy is commonly utilized for the treatment of deep-seated malignancies, such as brain tumors. In addition to tumor treatment, these particles may negatively impact healthy nerve cells. Therefore, it is essential to investigate the radiobiological effects of these radiations on cells. Simulation studies that model the radiation of heavy particles and the exact geometrical configuration of nerve cells are essential and effective in evaluating potential cellular damage.

The NEURON software was employed in Geant4 code to simulate an individual nerve cell (ID no: NMO 06176) and a network of ten neural cells subjected to bombardment by Ti48 ion particles at an energy of 600 MeV/u.

The absorbed energy differs among several components of individual cells and neural networks, including the soma and dendrites. The absorbed doses from Ti48 radiation in individual nerve cells and dendritic networks surpass those in the cell body, and this ratio remains consistent as the dosage escalates. The decrease in the initial length of dendrites in both individual cells and neuronal networks intensifies with increased dosages.

The simulation results demonstrate that dendrites absorb a higher radiation dose than the soma, resulting in greater structural damage. This finding highlights the vulnerability of neuronal networks to high-LET radiation, with important implications for space radiation protection and clinical radiotherapy planning.

The diminution of dendritic length due to Ti48 radiation is more significant within the cellular network compared to isolated nerve cells.

The ideal [¹³¹I]Sodium Iodide activity for intermediate-risk thyroid cancer treatment is still uncertain. The objective of this study is to compare the biochemical responses to radioiodine therapy (RIT) of intermediate-risk thyroid cancer patients administered [¹³¹I]Sodium Iodide at doses of 3700 MBq (100 mCi) and 5550 MBq (150 mCi).

A retrospective study was conducted by reviewing the medical records of intermediate-risk thyroid cancer patients who received RIT between 2016 and 2020 at a reference cancer hospital in Brazil. Sociodemographic and clinical data were evaluated at the time of diagnosis. Clinical data during two years of follow-up were reviewed, and biochemical responses were determined according to the American Thyroid Association (ATA, 2015 version). Responses to doses of 3700 MBq (100 mCi) and 5550 MBq (150 mCi) of [¹³¹I]Sodium Iodide were compared.

No significant statistical differences were observed concerning the biochemical therapeutic responses of patients treated with 3700 MBq or 5550 MBq (p = 0.088). The presence of nodal metastasis and positive pre-RIT thyroglobulin did not influence biochemical responses to radioiodine.

According to ATA 2015 guidelines, RIT may be administered to patients classified at intermediate risk for the ablation of post-surgical tissue remnants, as well as an adjuvant treatment for potential persistent tumor foci and to reduce recurrence risks. These recommendations, however, do not specify the appropriate radioiodine dosage and this has been a topic of extensive debate.

Intermediate risk thyroid-cancer patients presented similar therapeutic responses to the doses of 3700 MBq and 5550 MBq [¹³¹I]Sodium Iodide.

[⁶⁸Ga-DOTA-D-Phe1-Tyr3]octreotide ([⁶⁸Ga]Ga-DOTA-TOC) is a somatostatin analogue largely used in PET/CT applications for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NET). Initially, it was obtained using a ⁶⁸Ge/⁶⁸Ga generator. The increasing cost of good manufacturing practice-compliant generators has led to the need to find alternative ways of producing Gallium-68 (⁶⁸Ga). The aim of this work is to show the production optimization of [⁶⁸Ga]Ga-DOTA-TOC via cyclotron, derived from three years of experience.

The production of [⁶⁸Ga]GaCl3 via the ⁶⁸Zn(p,n)⁶⁸Ga reaction was optimized using a PETtrace 800 cyclotron (equipped with ZnO liquid target) and the synthesis of [⁶⁸Ga]Ga-DOTA-TOC was performed by FASTlab2 developer system according to the Guidelines on Good Radiopharmacy Practice (cGRPP). Quality control process was validated according to the current specific monograph (2482) of the European Pharmacopoeia (Ph. Eur.).

[⁶⁸Ga]Ga-DOTA-TOC was produced in 40 minutes; ten validation batches met the quality criteria expected by the Ph. Eur. The synthesis process has involved many issues due to the use of acidic reagents and related corrosion of some components of cyclotron and developer system, resulting in 12.2% failed syntheses and a target breakdown after 11 months.

The main issues, their causes and the strategies used to solve them are reported in the troubleshooting section: thanks to these strategies, the number of failed syntheses has decreased, and today, we have achieved a 0% failure rate.

Liquid target production of [⁶⁸Ga]Ga-DOTA-TOC, once consolidated, instead of ⁶⁸Ge/⁶⁸Ga generator has many advantages.

GLP-1 receptor agonists (GLP-1 RAs) are anti-diabetic agents known for their anti-inflammatory and antioxidant properties. This study investigates the synergistic effects of GLP-1 RAs and radiotherapy (RT) on breast cancer in a preclinical mouse model.

Female BALB/c mice were inoculated with 4T1 breast cancer cells and divided into five groups: control, placebo, GLP-1 RA alone, RT alone, and combination treatment. GLP-1 RA was administered intraperitoneally, and a single 8 Gy RT dose was applied. Tumor volumes, histopathological changes, cytokine expression, and apoptosis-related protein profiles were evaluated. In vitro, 4T1 cell viability was assessed following GLP-1 RA and/or RT exposure.

Combination therapy significantly reduced tumor volume compared to RT or GLP-1 RA alone. Histological analysis revealed improved tissue morphology with the combined approach. Immunohistochemical staining showed decreased expression of pro-inflammatory markers (IL-6, TNF-α) and angiogenic factors (VEGF-A, FGF-2), while pro-apoptotic proteins (caspase-3, BAD, p53) were elevated. In vitro findings confirmed a synergistic reduction in cell viability with combined treatment.

The results indicate that GLP-1 RAs potentiate the antitumor effect of RT in breast cancer, primarily through modulation of apoptosis and the tumor microenvironment.

GLP-1 RAs may be effective adjuvants to RT in breast cancer, particularly for patients with diabetes. The dual benefit of tumor sensitization and protection of normal tissues offers a promising therapeutic avenue.

The Ga68-DOTATATE PET/CT scan is an alternative imaging modality for the follow-up of children with neuroblastoma when the I123-MIBG scan was negative or weak. Somatostatin receptors (SSR) can be expressed in neuroblastoma lesions, and when this happens, targeting these receptors may be a good alternative to treating this disease in addition to conventional treatments. Our aim is to focus on the interpretation of one of the physiological tracer uptake sites, the uncinate process of the pancreas, using DW-MRI scans.

We present and discuss 4 cases with neuroblastoma for a technical note. Imaging scans for SSR were performed using Ga68-DOTATATE PET/CT, and all showed varying degrees of increased uptake at the uncinate process of the pancreas on PET/CT images. We also performed a DW-MRI study to distinguish physiologic uptake in this region of the pancreas from metastatic involvement.

Two of them showed diffusion restriction, with one of them also showing multiple masses within the liver. The other 2 children with high pancreatic uncinate process uptake did not exhibit any findings that indicated pancreatic involvement in the disease, based on DW-MRI images and clinical findings.

We recommend comparing DW-MRI scans and SSR-PET/CT scans to determine the true state of physiologically elevated SSR concentration and consequently indicate increased uptake on the images. The radiotracer concentration at the high uptake site did not appear to correlate with malignant involvement of the organ. The higher number of patients may allow a statistical comparison of the tracer with malignancy status.

Metformin induces radiation sensitivity in cancer cells, including colorectal cancer cells; however, the exact molecular mechanisms underlying its radiosensitive effects are not yet known. In this study, we investigated the role of the p53/miR-34a/SIRT1 pathway in the radiosensitivity of colon cancer cells.

The study was carried out from 2020 to 2022 at the Qazvin University of Medical Science's Cellular and Molecular Research Center. Two colorectal cancer cell lines (SW480 and SW620) obtained from primary and secondary tumors derived from a single patient were used as the study samples. After subjecting the cells to 50 Gy of radiation, we generated radioresistant cell lines. Resistant cells were treated with 50 µM metformin. Metformin-treated and untreated resistant cells constituted the study groups. The expression levels of miR-34-a and Sirtunin1 (SIRT1) were evaluated using Quantitative Real-time PCR. The rates of cell proliferation and apoptosis were assessed using a Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Western blot analysis was performed to quantify the expression of proteins. For statistical analysis, the Student's t-test was carried out to examine the mean differences between the two groups, and analysis of variance (ANOVA) was used to examine additional groups.

Our results showed that the expression of miR-34-a was downregulated (0.29 ± 0.11) in radiation-resistant cancer cells (P <0.001), while the expression of SIRT-1 was upregulated (4.5 ± 0.25) (P <0.001). Metformin increased the radiosensitivity of colon cancer cells in a time- and dose-dependent manner. Treatment with 50 µM metformin after 48h caused decreased cell viability and increased apoptosis in resistant cells. We observed downregulation of SIRT-1 (1.1 ± 0.45) and upregulation of miR-34-a (4.3 ± 1.3) (P <0.001) in metformin-treated cells. In contrast, western blotting results showed the upregulation of acetylated P53 in metformin-treated cells. Metformin function was reversed by SIRT1 inhibitors or by transfection with miR-34-a overexpressing plasmids.

Based on these results, one of the radiosensitivity mechanisms of metformin in colorectal cancer is the modulation of the p53/miR-34a/SIRT1 loop.