Usefulness of 99mTc–pertechnetate SPECT-CT in thyroid tissue volumetry: phantom studies and a clinical case series

Background: An accurate measurement of the target volume is of primary importance in theragnostics of hyperthyroidism Objective: Our purpose was to evaluate the accuracy of a threshold–based isocontour extraction procedure for thyroid tissue volumetry from SPECT-CT. Methods: Cylindrical vials with a fixed volume of 99mTcO4 at different activities were inserted into a neck phantom in two different thickness settings. Images were acquired by orienting the phantom in different positions, i.e., 40 planar images and 40 SPECT-CT. The fixed values of the iso-contouring threshold for SPECT and SPECT-CT were calculated by means of linear and spline regression models. Mean, Median, Standard Deviation, Standard Error, Mean Absolute Percentage Error and Root Mean-Square Error were computed. Any difference between the planar method, SPECT and SPECT-CT and the effective volume was evaluated by means of ANOVA and post-hoc tests. Moreover, planar and SPECT-CT acquisitions were performed in 8 patients with hyperthyroidism, considering relevant percentage differences greater than > 20 % from CT gold standard. Results: Concerning phantom studies, the planar method shows higher values of each parameter than the other two methods. SPECT-CT shows lower variability. However, no significant differences were observed between SPECT and SPECT-CT measurements. In patients, relevant differences were found in 7 out of 9 lesions with the planar method, in 6 lesions with SPECT, but in only one with SPECT-CT. Conclution: Our study confirms the superiority of SPECT in volume measurement if compared with the planar method. A more accurate measurement can be obtained from SPECT-CT.

Effect of pH variation on cross-linking of water-soluble and acid-soluble chitosan with sodium tripolyphosphate and gallium-67

Background: Chitosan is a cationic biopolymer obtained from deacetylating chitin, a naturally compoundpresent in crustacean shell, fungi and exoskeleton of insects. Chitosan has various applications including drug and gene delivery systems, wound dressing and as scaffolds for tissue engineering, agriculture, textile, food and feed nanotechnology, waste water treatments. chitosan-TPP particle figure out as the most important and stable nanoparticle for chitosan application in various fields. Objective: At this study chitosan was chemically modified by sodium tripolyphosphate (TPP). Afterward, TPP-chitosan was radiolabeled with gallium-67 radionuclide. The effect of several factors on labeling yield such as chitosan solubility, acidity and concentration of TPP-chitosansolution, incubation time with gallium-67 were investigated. Methods: To prepare [67Ga] gallium-chitosan complex, chitosan (0.5 ml) was dissolved in 2.2 mCi of [67Ga] gallium chloride solution. The obtained solution was stirred for 5 min and then was kept for 30 min at room temperature. Radiochemical purity and radiolabeling yield was measured via radiochromatography that it was performed by using a radio thin-layer chromatography (TLC) scanner instrument. To investigate the effect of chitosan kind and concentration on the labeling yield, two kinds of chitosan (acid-soluble chitosan and water-soluble chitosan) with two different concentrations (1% and 0.5%) at different pH were used. In addition, labeling efficiency and stability of the 67Ga-TPP-chitosan complex (acidic/water soluble chitosan) at both concentrations (0.5 and 1%) at room temperature was assessed for 30, 45 and 60 min. Results: The incubation time has not significant effect on labeling yield. The acidic soluble chitosan, which has highest radiolabeling yield at pH=9.3-10.4, water soluble chitosan showed the highest radiolabeling yields at pH > 5. Also, the prepared complex was stable in the final solution at room temperature and can even be used 24 hours after preparation for further application. Conclusion: Taken together, the TPP modified water soluble chitosan at concentration 0.5 % depicted the highest radiochemical yield (>95 %) at the optimized condition (pH= 6.2–7.6). Therefore, TPP modified water soluble chitosan can be an effective carrier for therapeutic radionuclides for tumor treatment.

Radiopharmaceutical preclinical investigation: an accurate and multidisciplinary approach

Background: The development of less expensive and pivotal methodologies, capable to support the researchers in the radiopharmaceutical pre-clinical investigations could provide a crucial incentive for developing biomedical research involved in the realization of tailored target therapies. Objective: The aim of this pilot study was to evaluate the capability of a digital autoradiography system equipped with a laser scanning device to perform [18F]choline biodistribution evaluation in a xenograft mouse model of prostate cancer. Methods: PC3 prostate cancer cells were used to develop xenografts in NOD/SCID mice. The biodistribution of the radiopharmaceutical was evaluated at 30,60 and 120 min after injection in excised organs by using a digital autoradiography system equipped with super resolution laser screen. Histological and immunohistochemical analysis were performed to correlate the [18F]choline uptake with morphological and molecular tumours characteristics. Results: Data here reported clearly indicate the possibility to perform accurate biodistribution studies by using the digital autoradiographic system equipped with a super resolution screen. Specifically, a significant increase in the [18F]choline inhibitor uptake in PC3 tumours as compared to heart, bowel, liver and kidney at both 30 and 60 min was observed. More important, the digital autoradiographic system showed signal uptake almost exclusively in the PC3 tumors at 60 min post-injection. Noteworthy, immunohistochemical analysis demonstrated a strong overlapping between the [18F]choline uptake and the proliferation index (Ki67 expression). Conclusions: The use of autoradiography system in pre-clinical investigations could shed new light on the molecular mechanisms that orchestrate the tissues damage induced by therapeutical radiopharmaceuticals.

Preclinical assessment of [68Ga]Ga-Cell Death Indicator (CDI): a novel hsp90 ligand for positron emission tomography of cell death

Background: 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (GSAO) when conjugated with a bifunctional chelator 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODAGA) (hereafter referred to as Cell Death Indicator [CDI]), enters dead and dying cells and binds to 90kDa heat shock proteins (hsp90). Objective: This study assesses stability, biodistribution, imaging, and radiation dosimetry of [68Ga]Ga-CDI for positron emission tomography (PET). Methods: Preparation of [68Ga]Ga-CDI was performed as previously described. Product stability and stability in plasma were assessed using high-performance liquid chromatography. Biodistribution and imaging were conducted in ten healthy male Lewis rats at 1 and 2 h following intravenous [68Ga]Ga-CDI injection. Human radiation dosimetry was estimated by extrapolation for a standard reference man and calculated with OLINDA/EXM 1.1. Results: Radiochemical purity of [68Ga]Ga-CDI averaged 93.8% in the product and 86.7% in plasma at 4 h post-synthesis. The highest concentration of [68Ga]Ga-CDI is observed in the kidneys; [68Ga]Ga-CDI is excreted in the urine, and mean retained activity was 32.4% and 21.4% at 1 and 2 h post-injection. Lower concentrations of [68Ga]Ga-CDI were present in the small bowel and liver. PET CT was concordant and additionally demonstrated focal growth plate uptake. The effective dose for [68Ga]Ga-CDI is 2.16E-02 mSv/MBq, and the urinary bladder wall received the highest dose (1.65E-02mSv/Mbq). Conclusions: [68Ga]Ga-CDI is stable and has favourable biodistribution, imaging, and radiation dosimetry for imaging of dead and dying cells. Human studies are underway.

Potential Utility of Radiopharmaceuticals in the Battle Against SARS-Cov-2 and COVID-19 Pandemic

: Coronavirus disease 2019 (COVID-19) pandemic, which has emerged in December 2019 in the city of Wuhan, China, has significantly affected healthcare systems and economies within a short timeframe. Treatment strategies offer alleviation of symptoms in the absence of commercially available specific antiviral agents. Within this context, the introduction of innovative therapeutic approaches against the SARS-CoV-2 virus is a critical need that should be addressed urgently. The anti-inflammatory effect of low dose irradiation has been proposed as a potential therapeutic strategy for COVID-19 pneumonia. Consideration of external beam irradiation for management of COVID-19 pneumonia has prompted the investigation of alternative methods of irradiation with potentially improved toxicity profiles. Theoretically, targeted radiotherapy may have several advantages over conventional external beam radiotherapy owing to the capability to deliver effective radiation doses without adverse irradiation effects. Since radionuclides are conjugated to targeting vectors, such as antibodies and cell surface receptor binding peptides, irradiation may be focused on targeted cells with optimal sparing of surrounding normal tissues. In the context of COVID-19 management, targeted irradiation is expected to compromise SARS-CoV-2 extracellular virions. Targeted radiotherapy may offer a viable means of combating against SARS-CoV-2 virus. There is room for improvement with the need for efficacy, feasibility, and toxicity studies. Although targeted radiotherapy itself may not achieve absolute eradication of virus or virus-infected cells, it may at least serve as a supplementary therapeutic strategy that could be utilized in combination with other antiviral treatments. Further investigations focusing on nuclear medicine, radiopharmaceuticals, and targeted radiotherapy strategies may pave the way for the development of efficacious antiviral treatments which may be utilized in the battle against the current COVID-19 pandemic.

Radioprotective effect of febuxostat against testicular damage induced by ionizing radiation in mice

Background: The testis is one of the most radiosensitive tissues in pelvic radiotherapy, especially in prostate cancer. Febuxostat (FBX), as an inhibitor of xanthine oxidase, has anti-inflammatory, antioxidant, and anti-apoptosis properties. Objectives: The aim of this research was to survey the protective effect of FBX against irradiation (IR)-induced testis damage via the attenuation of oxidative stress. Methods: Male adult mice were randomly assigned into eight groups: control, FBX with three doses of 5, 10, and 15 mg/kg, IR with 6 Gy, IR + FBX (IR + FBX in three doses), respectively. In the IR + FBX groups, FBX was administrated for 8 consecutive days, and then mice were exposed to IR at a dose of 6 Gy on the 9th day. One day after irradiation, biochemical parameters were evaluated in the testis of animals, while histopathological assessment had been performed on 14th day. Results: Irradiation led to the induction of testicular toxicity. FBX significantly protected histopathological alterations and decreased oxidative stress parameters in irradiated testis. Besides, FBX increased the diameter and germinal epithelial thickness of seminiferous tubules and Johnson’s score in irradiated mice. Conclusion: Data showed that FBX markedly protected testicular injury induced by IR by inhibiting oxidative stress and may be considered as an infertility inhibitor in cancer patients, especially prostate cancer.