Current Radiopharmaceuticals - Volume 16, Issue 2, 2023

This minireview describes the global situation of ongoing research and development and the clinical application of alpha emitter labeled immunoconjugates with various alpha emitters with an overview of the future trends. The potentially helpful alpha emitter radioisotopes for medical applications, chelators, and immunomolecules of interest for future alpha radioimmunotherapy are discussed. Challenges and some suggested future works on chelators are also presented.

In recent years, there has been an increased interest in ⁴⁴Ti/⁴⁴Sc generators as an onsite source of ⁴⁴Sc for medical applications without needing a proximal cyclotron. The relatively short half-life (3.97 hours) and high positron branching ratio (94.3%) of ⁴⁴Sc make it a viable candidate for positron emission tomography (PET) imaging. This review discusses current ⁴⁴Ti/⁴⁴Sc generator designs, focusing on their chemistry, drawbacks, post-elution processing, and relevant preclinical studies of the ⁴⁴Sc for potential PET radiopharmaceuticals.

Angiogenesis phenomenon, as a highly affecting factor on the growth and spread of cancer cells, depends on specific molecular interactions between components of the extracellular matrix and vascular cells. αv integrin acts as a cell adhesive molecule involved in tumor invasion and angiogenesis. Among the various combinations of integrin subunits expressed on the surface of cells, αvβ3 integrin has a particularly interesting expression pattern during angiogenesis. The αvβ3 integrin is a vital receptor affecting tumor growth, tumor invasiveness, metastasis, and angiogenesis overexpressed on various human tumors, leading to the development of different theranostics probes and radiopharmaceuticals. The αvβ3 integrin can recognize several extracellular matrix molecules in the base of the RGD adhesive sequence. This review provides an overview of the status, trends and future of the most studied αvβ3 integrin-binding ligand, RGD tripeptides, labeled with various radioisotopes. An overview of the pre-clinical models for radiolabeled RGD peptides and clinical aspects of the RGD- based radiopharmaceuticals is provided with some new considerations and ways forward.

Background: Glioblastoma is the most common primary malignant tumor of the central nervous system. The patient's median survival rate is 13.5 months, so it is necessary to explore new therapeutic approaches. Objective: Extremely low-frequency electromagnetic field (EMF) has been explored as a noninvasive cancer treatment. This study applied the EMF with previous conventional chemoradiotherapy for glioblastoma. Methods: In this study, we evaluated the cytotoxic effects of EMF (50 Hz, 100 G), temozolomide (TMZ), and radiation (Rad) on gene expression of T98 glioma cell lines in monolayer and spheroid cell cultures. Results: Treatment with Rad and EMF significantly increased apoptosis-related gene expression compared to the control group in monolayers and spheroids (p<0.001). The expression of apoptotic-related genes in monolayers was higher than the similar spheroid groups (p<0.001). We found that treatment with TMZ and EMF could increase the gene expression of the autophagy cascade markers compared to the control group (p<0.001). Autophagy-related gene expression in spheroids was higher than in the similar monolayer group (p<0.001). We demonstrated that coadministration of EMF, TMZ, and Rad significantly reduced cell cycle and drug resistance gene expression in monolayers and spheroids (p<0.001) compared to the control group. Conclusion: The combinational use of TMZ, Rad and, EMF showed the highest antitumor activity by inducing apoptosis and autophagy signaling pathways and inhibiting cell cycle and drug resistance gene expression. Furthermore, EMF increased TMZ or radiation efficiency.

Nuclear medicine specialty involves the administration of unsealed radioactive substances to patients to allow specific diagnostics and treatments using radiopharmaceuticals, radiotracers, and materials. Developing a radiopharmaceutical must involve considering and addressing some limitations such as its retention by unintended organs, which can influence patient and worker safety, imaging findings, and diagnostic and therapeutic accuracy. This paper presents data on the changing biodistribution, localization, stability, and accuracy patterns of radiopharmaceuticals by liposome encapsulation. Methods: Data are presented for 5 male New Zealand white rabbits. They were injected intravenously with the ^99mTc-liposomes encapsulated MIBI through a marginal ear vein, and whole-body images were acquired using a dual-head gamma camera. Cationic PEGylated liposomes were prepared using the conventional thin-film-hydration method. The liposomes were tested for particle size, zeta potential, high-performance-liquid-chromatography (HPLC), and toxicity. Results: The liver activity was slightly greater than or equivalent to heart uptake, using ^99mTcsestamibi, MIBI, without liposome as a reference. The absorbed doses in myocardium cells after injecting rabbits with ^99mTc-MIBI labeled with free positive lower pH liposomes was greater than in the liver, whereas ^99mTc labeled with encapsulated MIBI within positive liposomes showed a significantly higher heart-to-liver ratio. The heart-to-spleen activity uptake ratio in ^99mTc-MIBI was higher than or equal to one but increased in ^99mTc labeled with MIBI and free positive liposomes. Injecting rabbits with ^99mTc labeled with encapsulated MIBI raised myocardium uptake to 2-4 times more than the spleen. Heart-to-bowel activity began to rise with 99m Tc-labeld-MIBI and liposomes. Conclusion: This study provides findings in radiopharmaceutical biodistribution using liposomal agents. Adding free liposomes using a pH gradient technique enhanced the uptake and localization of the radiotracer. However, tracer encapsulation during the formation of the liposomes showed even better specificity.

Background: In recent years, there has been a significant increase in studies investigating the potential use of plant-origin products in the treatment and diagnosis of different types of cancer. Methods: In this study, Estragole (EST) was isolated from basil leaves via ethanolic extraction using an 80% ethanol concentration. The isolation process was performed using the High Performance Liquid Chromatography (HPLC) method. The EST isolated from the basil plant was radiolabeled with ¹³¹I using the iodogen method. Quality control studies of the radiolabeled EST (¹³¹IEST) were carried out by using Thin Layer Radio Chromatography (TLRC). Next, in vitro cell, culture studies were done to investigate the bio-affinity of plant-originated EST labeled with ¹³¹I on human medulloblastoma (DAOY) and human glioblastoma-astrocytoma (U-87 MG) cell lines. Finally, the cytotoxicity of EST was determined, and cell uptake of ¹³¹I-EST was investigated on cancer cell lines by incorporation studies. Results: As a result of these studies, it has been shown that ¹³¹I-EST has a significant uptake on the brain cells. Conclusion: This result is very satisfying, and it has encouraged us to do in vivo studies for the molecule in the future.

Aims: We aim to reveal an effect of residual activity leftover within the medical materials other than the empty syringe used for injection of the tracer on SUV measurements and consequently effect on possible treatment response assessment. Background: Staging and follow-up of pediatric lymphoma patients mainly achieved by the help of PET/CT scans. It is crucial to make an optimal imaging technique for interpreting individual images and assessing treatment response. Objective: Standardized uptake value measurement is an important quantification parameter in PET/CT scanning of childhood lymphomas. Low dose of activity used in pediatric oncology patients makes them vulnerable to small changes of input values for subsequent metabolic parameters. Methods: Sixty-eight pediatric lymphoma patients below 50 kg were included into the study. SUVmax, SUVpeak values of the most metabolically active lesions, along with liver and mediastinum, were recorded. Metabolic parameters of the lesions/lymph nodes, mediastinum and liver parenchyma were compared before and after counts from medical materials other than empty syringe were taken into account. Wilcoxon signed-rank test was used for non-parametric paired sampled tests for the groups. Results: There were statistically significant differences between the whole 6 above-mentioned groups confirming the importance of residual counts on metabolic parameters (p < 0.001). Conclusion: Our study demonstrated residual radioactivity in medical materials such as serum line tubes, i.v. catheters, three-way stopcock and also butterfly needles used during intravenous injection should also be included for optimum quantitative metabolic parameter values and to minimize its the adverse effect on treatment response evaluation, especially in borderline lesions.

Introduction: F18 and Ga68 radioisotopes are used in PET imaging for prostate cancer. It was aimed to calculate the prostate, testicle and bladder effective doses (ED) caused by F18 and Ga68 used in prostate cancer imaging with PET/CT via simulation with the GATE toolkit and evaluate the ED in terms of fertility. Methods: The prostate, testicle and bladder were defined together with their geometric properties and densities in GATE simulation. F18 and Ga68 with activity of 277.5 MBq and 151.7 MBq were identified in the prostate as a source organ. The ED, uncertainties, and S values were taken as an output file in the TXT format with the DoseActors command. S values were used for validation of the simulation. Results: The ED of the prostate, total testicle and bladder for F18 were found to be 6.627E-04 ± 1.799E-06, 12.74E-07 ± 4.11E-08 and 1.617E-05 ± 4.317E-09 (Gy/s), respectively. The ED of the prostate, total testicle, and bladder for Ga68 were found to be 9.195E-04 ± 2.660E-06, 6.54E-07 ± 2.93E-08 and 4.290E-05 ± 6.936E-09 (Gy/s), respectively. Conclusion: It was found that Ga68 produced high prostate and bladder ED, and F18 produced high testicular ED. In terms of male fertility, Ga68 seems to be a good alternative because it produces low testicular doses. The ED of the testicle both F18 and Ga68 were below the reported spermatogonia and azoospermia dose.

Background: New generation PET/CT devices provide quality images using low radiopharmaceutical activities. Dose monitoring is carried out for nuclear medicine personnel, other health personnel, and companions by determining the radiation dose emitted from low-activity patients to the environment. In particular, it is necessary to revise the working conditions of the personnel according to the radiation dose exposed. Aim: It was aimed to reevaluate the radiation dose rate transmitted to the environment from patients injected with ¹⁸F-FDG. Materials and Methods: A total of 31 patients (14F, 17M) who underwent ¹⁸F-FDG PET/CT imaging were included. The mean ¹⁸F-FDG activity of 7.26 ± 1.29 mCi was used for injection. After injection, radiation dose rates (mR/h) were measured at distances of 25, 50, 100, 150, and 200cm for 3 different periods from the level of the head, thorax, abdomen, and pelvis by using a GM counter. Additionally, biological samples such as urine and sweat were taken during 3 different periods. The activity amounts (μCi) in the samples were measured with a well-type counter. Results: Strong correlations were calculated between normalized dose rates obtained by all regions and time. Considering the nuclear medicine staff handling time with a PET/CT patient, the average dose received by staff was calculated between a range of 0.002-0.004 mSv/pt. The radiation dose exposed to the porter and nurse was calculated as 0.049 mSv/pt for the 2^nd hour and 0.001-0.007 mSv/pt for the 4^th hour, respectively. The companion was exposed to a dose between 0.073-0.147 mSv and 0.024-0.048 mSv for public transport and private car transportation after 4-6 hours of injection (for 30-60 min of travel duration), respectively. For inpatients, the received dose for porters, serving 20min from a distance of 30cm for the 2^nd and 4^th hours after the PET/CT scan, was 0.049 mSv/pt and 0.048 mSv/pt, respectively. And for nurses serving from a 50cm distance between 1-5 minutes, these values were found to be 0.001-0.007mSv/pt, 0.001-0.007mSv/pt, and 0.001-0.006mSv/pt, respectively. Conclusion: The radiation dose of nuclear medicine staff, porters, nurses, and companions are found to be below the recommended dose limit by the ICRP. According to our results, there is no need for any restrictions for patients, companions, or healthcare personnel in PET/CT units.