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Montelukast, a leukotriene receptor antagonist with a high affinity and selectivity for the cysteinyl leukotriene receptor type-1, was radiolabeled with 99mTc using a direct tagging procedure. The processing parameters—amounts of both montelukast and reducing agent, pH of the reaction mixture, reaction temperature, time of reaction, and in vitro stability of the 99mTc-montelukast complex—were thoroughly investigated. The 99mTc-montelukast complex had a percent radiolabeling yield of 92 ± 0.23 and an in vitro stability of 6 hours. According to biological distribution studies, the maximum uptake of 99mTc-montelukast complex for the lungs was 35.89 ± 1.03 % injected activity/gm tissue at 15 minutes following injection and remained high in the lungs for another hour (15.88 ± 0.39%), whereas the washout of mice organs appeared to primarily occur via the urinary tract. Because the 99mTc-montelukast complex is not a blood product, it is safer. To summarize, the 99mTc-montelukast complex is a new radiopharmaceutical that might be utilized for perfusion imaging of the lungs that is both safer and more useful. [ABSTRACT FROM AUTHOR]

This study aimed to assess the biodistribution and bioactivity of the affibody molecular probe 99mTc-(HE)3ZHER2:V2, prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.

Due to the excellent nuclear properties，99mTc has been used in the field of early diagnosis of tumor and nuclear medicine imaging. As the most widely applied radioisotope，it accounts for more than 70% of the market of total radioisotopes used in the nuclear medicine diagnosis. Until now，99mTc in clinical has been prepared by the 99Mo-99mTc generators. To improve the disadvantages of current technologies including unstable supplement of the fission 99Mo for the fission-type 99Mo-99mTc generator and long production time for the gel-type 99Mo-99mTc generator，a new irradiated-type 99Mo-99mTc generator filled with the Ti99Mo has been developed. The effects of the chemical agents，Mo:Ti molar ratio，dry methods on the elution properties of the Ti99Mo-based 99Mo-99mTc generator were investigated. Based on the results of simulation experiments and performance tests，the elution from the irradiated-type 99Mo-99mTc generator was found to be accorded with medical standard. During the seven elution processes，the radionuclidic purity of sodium technetium-99m solution was above 99.92%，the radiochemical purity was higher than 98.8%，the pH value was between 5.0 and 6.0 and the average elution efficiency reached 72.07%，the peak of elute curve was located at 2-4 mL without the phenomenon of trailing，showing the excellent performance. The synthesized preparation has been advanced before the process of irradiation by the reactor，to simplify the operational radioactive procedures，shorten the production time，increase the elution efficiency of the generator and decrease the loss of 99Mo decay.

Abstract Background The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms. Methods Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed. Results The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes. Conclusions Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT.

Introduction: Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods: IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion: The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys joints and cartilage, resulting in synovitis and pannus formation. Timely detection and effective management of RA are pivotal for mitigating inflammatory arthritis consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents a promising avenue for RA diagnosis and response to treatment assessment. Radiopharmaceutical such as technetium-99m (99mTc), combined with single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), introduces a more refined diagnostic approach, enhancing accuracy through precise anatomical localization, representing a notable advancement in hybrid molecular imaging for RA evaluation. This comprehensive review discusses existing research, encompassing in vitro, in vivo, and clinical studies to explore the application of 99mTc radiolabeled targeting vectors with SPECT imaging for RA diagnosis. The purpose of this review is to highlight the potential of this strategy to enhance patient outcomes by improving the early detection and management of RA. [ABSTRACT FROM AUTHOR]

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn− lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn− tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery. [ABSTRACT FROM AUTHOR]

The aim of this study is to compare the efficiency and accumulation of 99mTc attached to iron oxide nanoparticles (IONPs) for use in the SPECT imaging. A comprehensive literature search identified 13 relevant studies, and the maximum absorbed dose per gram (ID/g) of [99mTc] Tc-IONPs in various organs at different time intervals was analyzed. The findings showed the distribution patterns of the compounds in each organ, emphasizing the significance of coating and nanoparticle size for optimal imaging results. By selecting the appropriate coating and nanoparticle size, imaging quality and accuracy can be improved. [ABSTRACT FROM AUTHOR]

Background: The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms. Methods: Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed. Results: The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes. Conclusions: Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT. [ABSTRACT FROM AUTHOR]

Abstract Background 99mTc radiolabeled nanobody NM-02 (99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99mTc-NM-02 uptake and HER2 expression in patients with breast cancer. Methods Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99mTc-NM-02 SPECT/computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUVmax) of 18F-FDG and SUVmax and mean SUV (SUVmean) of 99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. Results No meaningful relationship was observed between 18F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18F-FDG PET/CT. 99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. Conclusions 99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. Trial registration NCT04674722, Date of registration: December 19, 2020.

Abstract Targeting receptors overexpressed on cancer cells with radiolabeled peptides has become a crucial aspect of molecular imaging in oncology. Small peptides offer favorable characteristics for tumor targeting with minimal side effects and toxicity owing to their small size and simple radiolabeling protocols. Among them, somatostatin analogs have received regulatory approval for the diagnosis and treatment of neuroendocrine tumors. Cyclic RGD (Arg‐Gly‐Asp) peptides, bombesin analogs, and glucagon‐like peptide‐1 analogs are currently under development and/or undergoing clinical trials. The most used radionuclides for tumor imaging include 99mTc and 111In for single‐photon emission computed tomography, 68Ga and 18F for positron emission tomography. This review highlights the clinical potential and future prospects of 99mTc‐labeled peptides for tumor imaging.

Background: 99mTc radiolabeled nanobody NM-02 (99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99mTc-NM-02 uptake and HER2 expression in patients with breast cancer. Methods: Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99mTc-NM-02 SPECT/computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUVmax) of 18F-FDG and SUVmax and mean SUV (SUVmean) of 99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. Results: No meaningful relationship was observed between 18F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18F-FDG PET/CT. 99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. Conclusions: 99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. Trial registration: NCT04674722, Date of registration: December 19, 2020. [ABSTRACT FROM AUTHOR]

Aβ42 plaque formation is one of the preliminary pathologic events that occur post traumatic brain injury (TBI) which is also among the most noteworthy hallmarks of AD. Their pre symptomatic detection is therefore vital for better disease management. Chalcone–picolinic acid chelator derivative, 6‐({[(6‐carboxypyridin‐2‐yl)methyl](2‐{4‐[(2E)‐3‐[4‐(dimethyl amino)phenyl]prop‐2‐enoyl]phenoxy}ethyl)amino}methyl)pyridine‐2‐carboxylic acid, Py-chal was synthesized to selectively identify amyloid plaques formed post head trauma using SPECT imaging by stable complexation to 99mTc with > 97% efficiency without compromising amyloid specificity. The binding potential of the Py-chal ligand to amyloid plaques remained high as confirmed by in vitro binding assay and photophysical spectra. Further, the Py-chal complex stained amyloid aggregates in the brain sections of rmTBI mice model. In vivo scintigraphy in TBI mice model displayed high uptake followed by high retention while the healthy rabbits displayed higher brain uptake followed by a rapid washout attributed to absence of amyloid plaques. Higher uptake in brain of TBI model was also confirmed by ex vivo biodistribution analysis wherein brain uptake of 3.38 ± 0.2% ID/g at 2 min p.i. was observed for TBI mice model. This was followed by prolonged retention and more than twofold higher activity as compared to sham mice brain. This preliminary data suggests the specificity of the radiotracer for amyloid detection post head trauma and applicability of 99mTc labeled Py-chal complex for TBI-induced β-amyloid SPECT imaging. [ABSTRACT FROM AUTHOR]

To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging. [ABSTRACT FROM AUTHOR]

Background and purpose: The selection of co-ligand has a profound effect on the labeling efficiency, biodistribution, and tumor-targeting ability of 99mTc-labeled HYNIC-conjugated peptides. This study compared the in-vitro and in-vivo properties from the 99mTc-labeling of 6-Hydrazinonicotinamide-conjugated neurotensin (HYNIC-[βAla7-Tle12] NT (5-13)) by Tricine/EDDA and Tricine as two co-ligand systems. Materials and methods: After radiolabeling, cellular specific binding, affinity and internalization were evaluated toward the HT-29 cell line, as neurotensin overexpressing cells for both of them. Finally, the biodistribution studies were performed on HT-29 xenografted tumor-bearing nude mice, and the imaging was performed using a gamma camera. Results: The radiochemical purity of 99mTc labeled peptide with tricine and tricine/EDDA as co-ligands was found over 95%, and they showed desirable saline and serum stability up to 24 h. The dissociation constant (Kd) value for radiolabeled peptide with tricine and tricine/EDDA toward NT receptors were determined as 50.41 ± 9.76 and 32.66 ± 4.00, respectively. Internalization of radiolabeled peptide with tricine/EDDA was reported almost 2-fold more than radiolabeled peptide with tricine as co-ligand for HT-29 cell line after 4 h incubation. In biodistribution and imaging, the tumor/muscle activity ratio was 2.30 and 4.20, 1.74 and 2.28 at 2 h post-injection with tricine and tricine/EDDA, respectively. Conclusion: Despite relatively similar radiochemical properties of both peptide radio-complexes with 99mTc, the complex labeled with a mixture of tricine/EDDA as co-ligands showed more suitable in vivo properties than tricine.

This study aimed to create a novel bimodal probe. For this purpose, cubic iron oxide nanoparticles (C-Fe3O4 NPs) conjugated with an EDTMP derivative called DPAPA thought to be a targeting tool for prostate cancer and bone metastases were studied. NPs were synthesized and conjugated with DPAPA, and then characterization studies were carried out. The particles were demonstrated to be cubic shaped, with an average size of 68.55 ± 1 0.03 (n = 3) nm. Then the nanoconjugates were radiolabeled with 99mTc. In vitro cellular affinities were conducted using PC-3, RWPE-1, LNCaP, K562, and Saos-2 cell lines. In conclusion, radio-nanoconjugates have the potential for bimodal MRI/SPECT imaging. [ABSTRACT FROM AUTHOR]

This study measured 99mTc-MDP bone scintigraphy radiation risks, as low-dose radiation exposure is a growing concern. Dosimeter measurements were taken at four positions (left lateral, right lateral, anterior, and posterior) around the patients at 30, 60, 100, and 200 cm at 0, 1.5, and 3 h. The highest dose rates were recorded from 51% of the patients, who emitted ≥ 25 µSv/h up to 49.00 µSv/h at the posterior location at a distance of 30 cm. Additionally, at the anterior location at a distance of 30 cm, 42% of patients emitted ≥ 25 µSv/h up to 38.00 µSv/h. Furthermore, at 1.5 h after the tracer injection, 7% of the dose rates exceeded 25 µSv/h. There was a significant reduction in mean dose rates for all positions as distance and time increased (p-value < 0.05). As a result, radiation levels decreased with increased distance and time as a result of radiation decay, biological clearance, and distance from the source. In addition, increasing the distance from the patient for all positions reduced the radiation dose, as was substantiated via exponential regression analysis. Additionally, after completing the bone scintigraphy, the patients' dose rates on discharge were within the current guidelines, and the mean radiation doses from 99mTc-MDP were below occupational limits. Thus, medical staff received less radiation than the recommended 25 μSv/h. On discharge and release to public areas, the patients' mean dose rates were as follows: 1.13 µSv/h for the left lateral position, 1.04 µSv/h for the right lateral, 1.39 µSv/h for the anterior, and 1.46 µSv/h for the posterior. This confirms that if an individual was continuously present in an unrestricted area, the dose from external sources would not exceed 20 µSv/h. Furthermore, the patients' radiation doses were below the public exposure limit on discharge. [ABSTRACT FROM AUTHOR]

BackgroundPeritoneal dialysis (PD) is a common treatment method for patients with renal failure. While peritonitis and tube floating migration are commonly observed complications, visceral perforation caused by PD is relatively rare. We present a case report of a patient undergoing PD due to renal failure, who encountered two instances of visceral perforation. In both occurrences, Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) played a pivotal role in providing accurate diagnoses and precise localization of the perforation sites. This report underscores the paramount significance of SPECT/CT in diagnosing visceral perforations in the context of PD.Case presentationA 73-year-old elderly male has been undergoing PD for 1 year due to renal failure. Recently, there has been impaired drainage of the PD catheter. The clinical team suspected the occurrence of peritonitis. The patient underwent a 99mTc Sodium Pertechnetate (99mTc-NaTcO4) SPECT/CT examination, which identified intestinal perforation. After 20 days of conservative treatment, a SPECT/CT follow-up examination revealed the resolution of the intestinal perforation, but a new bladder perforation emerged. The dialysis catheter was methodically and gradually withdrawn in stages while simultaneously performing bladder decompression. Following these interventions, the patient remained free from peritonitis and cystitis.ConclusionThe utilization of SPECT/CT proved to be highly valuable in the accurate diagnosis of visceral perforation, a relatively rare complication observed in PD patients.

Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using 99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.

The purpose of this study is to perform radiation monitoring by acquiring gamma images and real-time optical images for 99mTc vial source using charge couple device (CCD) cameras equipped with the proposed compact gamma camera. The compact gamma camera measures 86 × 65 × 78.5 mm3 and weighs 934 g. It is equipped with a metal 3D printed diverging collimator manufactured in a 45° field of view (FOV) to detect the location of the source. The circuit's system uses system-on-chip (SoC) and field-programmable-gate-array (FPGA) to establish a good connection between hardware and software. In detection modules, the photodetector (multi-pixel photon counters) is tiled at 8 × 8 to expand the activation area and improve sensitivity. The gadolinium aluminium gallium garnet (GAGG) measuring 0.5 × 0.5 × 3.5 mm3 was arranged in 38 × 38 arrays. Intrinsic and extrinsic performance tests such as energy spectrum, uniformity, and system sensitivity for other radioisotopes, and sensitivity evaluation at edges within FOV were conducted. The compact gamma camera can be mounted on unmanned equipment such as drones and robots that require miniaturization and light weight, so a wide range of applications in various fields are possible.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys joints and cartilage, resulting in synovitis and pannus formation. Timely detection and effective management of RA are pivotal for mitigating inflammatory arthritis consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents a promising avenue for RA diagnosis and response to treatment assessment. Radiopharmaceutical such as technetium-99m (99mTc), combined with single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), introduces a more refined diagnostic approach, enhancing accuracy through precise anatomical localization, representing a notable advancement in hybrid molecular imaging for RA evaluation. This comprehensive review discusses existing research, encompassing in vitro, in vivo, and clinical studies to explore the application of 99mTc radiolabeled targeting vectors with SPECT imaging for RA diagnosis. The purpose of this review is to highlight the potential of this strategy to enhance patient outcomes by improving the early detection and management of RA.

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel 99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable 99mTc-complexes ([99mTc]Tc-L1, [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5). Corresponding rhenium analogues of [99mTc]Tc-L1 were synthesised and suggested the structures of these 99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel 99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five 99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging. [ABSTRACT FROM AUTHOR]

Nocardiotide-A (cWIWLVA) is a cyclic peptide with significant cytotoxicity against several cancer cells. The present research aimed to design a radiopeptide based on nocardiotide-A analogues to be labeled by technetium-99m targeting SSTR2, which is the most widely expressed receptor in several types of human cancers and used as radiopeptide target. Nocardiotide-A analogues were individually designed by replacing valine at the lead compound with lysine, arginine, histidine, asparagine, and glutamine, and this was simulated by molecular dynamics using AMBER18. A molecular docking using AutoDock 4.2 was performed and evaluated to understand the effect of chelation of technetium-99m on 99mTc-HYNIC-EDDA and 99mTc-HYNIC-tricine on the binding affinity of nocardiotide-A analogues. The molecular dynamics simulation confirmed that the designed nocardiotide-A-based peptides were stable in the binding pocket of SSTR2 for 200 ns. Moreover, the nocardiotide-A-based radiopeptides are able to interact with residues Q102, D122, Q126, and N276 by building hydrogen bonds, which are essential binding residues in SSTR2. The molecular docking simulation revealed that the best docking parameter is exhibited by 99mTc/EDDA/HYNIC-cWIWLNA and 99mTc/tricine/HYNIC-cWIWLNA with a binding free energy of –12.59 kcal/mol and –8.96 kcal/mol, respectively. Taken together, nocardiotide-A-based radiopeptides are prospective to be further developed for cancer imaging targeting SSTR2.

Abstract Background Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. Methods A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. Results Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P

To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.

IntroductionProstate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer.MethodsIONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP).Results and DiscussionThe MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging.

Nocardiotide-A (cWIWLVA) is a cyclic peptide with significant cytotoxicity against several cancer cells. The present research aimed to design a radiopeptide based on nocardiotide-A analogues to be labeled by technetium-99m targeting SSTR2, which is the most widely expressed receptor in several types of human cancers and used as radiopeptide target. Nocardiotide-A analogues were individually designed by replacing valine at the lead compound with lysine, arginine, histidine, asparagine, and glutamine, and this was simulated by molecular dynamics using AMBER18. A molecular docking using AutoDock 4.2 was performed and evaluated to understand the effect of chelation of technetium- 99m on 99mTc-HYNIC-EDDA and 99mTc-HYNIC-tricine on the binding affinity of nocardiotide-A analogues. The molecular dynamics simulation confirmed that the designed nocardiotide-A-based peptides were stable in the binding pocket of SSTR2 for 200 ns. Moreover, the nocardiotide-A-based radiopeptides are able to interact with residues Q102, D122, Q126, and N276 by building hydrogen bonds, which are essential binding residues in SSTR2. The molecular docking simulation revealed that the best docking parameter is exhibited by 99mTc/EDDA/HYNICcWIWLNA and 99mTc/tricine/HYNIC-cWIWLNA with a binding free energy of --12.59 kcal/mol and --8.96 kcal/mol, respectively. Taken together, nocardiotide- A-based radiopeptides are prospective to be further developed for cancer imaging targeting SSTR2. [ABSTRACT FROM AUTHOR]

The aim of present study was to determine the efficiency of commercially available PEG-based resins for separation of 99mTc from irradiated 100Mo target. Stable and radioactive tracer studies demonstrated that these PEG-based resins have extreme selectivity toward ReO4− (99mTcO4−) over MoO42− ions. Moreover, PEG-based resins still have 95% adsorption efficiency even after 600 kGy γ-irradiation, suggesting the excellent irradiation stability. The adsorption rate of ReO4− and 99mTcO4− rapidly increased to 90% in 10 s. Subsequently, three-column chromatographic processing based on these superior resins for isolating 99mTc was developed and examined. The separation investigation of 99mTc medical radioisotope produced by 100Mo(p, 2n)99mTc reaction was successfully performed. The recovery yield and the radionuclidic purity of 99mTc was about 90% and 99.9%, respectively. Moreover, the separation of 99mTc from a low specific activity 99Mo was also investigated. We are excited about the potential of this procedure with these accessible commercial availability PEG-based resins to address 99mTc separation problems and increase access to medical nuclide 99mTc for the general community. [ABSTRACT FROM AUTHOR]

Nuclear cardiology plays an important role in management of cardiac patients with known or suspected coronary artery disease (CAD). CAD is the leading cause of premature death and permanent disability. Myocardial perfusion imaging (MPI) with radiotracers is a non-invasive technique that shows the heart function and the areas of perfusion defects. In order to evaluate perfusion defects accurately, the radiotracer used in MPI studies must be taken up into myocardium in proportion to the regional myocardial blood flow. At present, 99mTc-TEBO is commonly used in clinic for rapid myocardial perfusion imaging, which has high initial uptake but poor myocardial retention, so it is necessary to optimize its structure. In this study, a group of novel 99mTc-labeled rapid boric acid derivatives tracers for myocardial perfusion imaging, including 99mTc-2SP, 99mTc-4LPA and 99mTc-2MDM were prepared in this study. The preparation time of these tracers was 30 min, and all of them were colorless clear liquid. The radiochemical purity of the three tracers was > 95%, respectively. The above tracer agents were used to perform SPECT dynamic imaging in healthy miniature pigs and compared with 99mTc-TEBO. After 99mTc-TEBO injection, rapid uptake was shown in left ventricular myocardium within 0.5 min, but the myocardial radioactivity decreased rapidly to about 75% of the peak value and the ratio of the radioactivity between myocardium/blood pool was 1.63 at 10 min. Compared with 99mTc-TEBO, 99mTc-2SP had prolonged retention and slower elution in myocardium within 15 min after the injection when the 2-methylsulfonyl pyridine-5-boric acid group was introduced into the 99mTc-2SP structure. The myocardial radioactivity still maintained 95% of the peak value, and the ratio of radioactivity between myocardium/blood pool was 3.75, which was significantly higher than that of 99mTc-TEBO. However, the other two imaging agents 99mTc-4LPA and 99mTc-2MDM showed poor uptake in myocardium within 15 min after injection. In conclusion, 99mTc-2SP was an ideal boric acid derivatives tracers for myocardial perfusion imaging and has prospect for clinical application in future.

Simple Summary: Prostate and breast cancers are the most common malignancies. Accurate diagnosis and staging of diseases are important for the prognosis and determination of treatment tactics. The gastrin-releasing peptide receptor is overexpressed in over 80% of estrogen receptor-positive breast cancers and in up to 100% of primary prostate cancers, particularly in prostate cancers of lower grades and smaller sizes. Our group has developed an imaging agent [99mTc]Tc-maSSS-PEG2-RM26 suitable for the detection of gastrin-releasing peptide receptors' expression using SPECT. We aimed to perform a first-in-human study to test the safety of [99mTc]Tc-maSSS-PEG2-RM26 administration, to study its biological distribution in normal organs, and to evaluate the agent's targeting of receptors in tumors. This phase I study was performed in six prostate and seven breast cancer patients. Single injections of the new agent were well tolerated and a number of prostate and breast cancer primary tumors as well as metastases were visualized with SPECT/CT shortly after administration. The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [99mTc]Tc-maSSS-PEG2-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 µg of [99mTc]Tc-maSSS-PEG2-RM26 (600–700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [99mTc]Tc-maSSS-PEG2-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 ± 0.0007 for male patients and 0.008 ± 0.003 mSv/MBq for female patients. The accumulation of [99mTc]Tc-maSSS-PEG2-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [99mTc]Tc-maSSS-PEG2-RM26 was safe and well tolerated. [99mTc]Tc-maSSS-PEG2-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies. [ABSTRACT FROM AUTHOR]

The physico-chemical properties of drug loaded nanoparticles (NPs) are important determinants for in vivo distribution, serum stability, and drug delivery efficiency. Liposomal NPs are most widely used due to their bicompability nature and drug carrier efficiency. In this study, 99mTc-labelled docetaxel (DTX) loaded folic acid-thiolated chitosan enveloped liposomal nanoparticles were synthesized and assessed for its localization, stability, and drug release in animal model. Folic acid grafted with thiolated chitosan was cross-linked with docetaxel and coated in liposomes (FTD-Lip). The radiolabelling efficiency of 99mTc-FTD-Lip was 98.8% with 97.2% serum stability. The in vivo distribution of 99mTc-FTD-Lip given by oral route showed that complex was localized in the buccal cavity, gastric fundus, and distal esophagus, with 20.2% DTX released after 5 h, while by intravenous route administration, the radio-complex was localized in the lungs and liver and 29.2% DTX release was observed after 5 h. 99mTcFTD-Lip can be used for site specific localization and comparative study indicates that intravenous drug release is higher than oral route while oral route shows steady drug release. The docetaxel grafted with chitosan and TGA were encapsulated in liposome that was further labelled with 99mTc. The in vivo distribution in rabbits acquired by gamma camera showed localized of complex in gastric fundus in case of oral rout administration while by intravenous administration complex was localized in lungs and liver. Slow release of docetaxel inside the body was also observed. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies indicate that 99mTc- and fluorescent-labeled c[Cys-Thr-Pro-Ser-Pro-Phe-Ser-His-Cys]OH (TCP-1) peptides were able to detect colorectal cancer (CRC) and tumor-associated vasculature. This study was designed to characterize the targeting properties of PEGylated and non-PEGylated TCP-1 peptides for CRC imaging. Procedures: Cell uptake of cyanine 7 (Cy7)-labeled TCP-1 probes (Cy7-PEG4-TCP-1 and Cy7-TCP-1) was investigated in three CRC cell lines (human, HCT116 and HT29; mouse, CT26). Xenograft and orthotopic CRC tumor models with HCT116 and CT26 cells were used to characterize biodistribution and CRC tumor-targeting properties of TCP-1 fluorescence and radioligand with and without PEGylation, [99mTc]Tc-HYNIC-PEG4-TCP-1 vs. [99mTc]Tc-HYNIC-TCP-1. Results: Fluorescence images showed that TCP-1 probes were distributed in the cytoplasm and nucleus of CRC cells. When CT26 cells were treated with unlabeled TCP-1 peptide prior to the cell incubation with Cy7-PEG4-TCP-1, cell fluorescent signals were significantly reduced relative to the cells without blockade. Relative to Cy7-TCP-1, superior brilliance and visibility of fluorescence was observed in the tumor with Cy7-PEG4-TCP-1 and maintained up to 18 h post-injection. [99mTc]Tc-HYNIC-PEG4-TCP-1 images in xenograft and orthotopic CRC models demonstrated that TCP-1 PEGylation preserved tumor-targeting capability of TCP-1, but its distribution (%ID/g) in the liver and intestine was higher than that of [99mTc]Tc-HYNIC-TCP-1 (1.51 ± 0.29 vs 0.53 ± 0.12, P < 0.01). Better tumor visualization by [99mTc]Tc-HYNIC-TCP-1 was observed in the orthotopic CRC model due to lower intestinal radioactivity. Conclusions: TCP-1-based probes undergo endocytosis and localize in the cytoplasm and nucleus of human and mouse CRC cells. Tumor detectability of fluorescent TCP-1 peptide with a PEG4 spacer is promising due to its enhanced tumor binding affinity and rapid clearance kinetics from nontumor tissues. Non-PEGylated [99mTc]Tc-HYNIC-TCP-1 exhibits lower nonspecific accumulation in the liver and gastrointestinal tract and might have better capability for detecting CRC lesions in clinical sites. TCP-1 may represent an innovative targeting molecule for detecting CRC noninvasively. [ABSTRACT FROM AUTHOR]

Nuclear imaging is a highly sensitive and noninvasive imaging technique that has become essential for medical diagnosis. The use of radiolabeled nanomaterials capable of acting as imaging probes has shown rapid development in recent years as a powerful, highly sensitive, and noninvasive tool. In addition, quantitative single-photon emission computed tomography (SPECT) images performed by incorporating radioisotopes into nanoparticles (NPs) might improve the evaluation and the validation of potential clinical treatments. In this work, we present a direct method for [99mTc]Tc-radiolabeling of FITC-tagged silk fibroin nanoparticles (SFN). NPs were characterized by means of dynamic light scattering and scanning electron microscopy. In vitro studies were carried out, including the evaluation of stability in biological media and the evaluation of hemocompatibility and genotoxicity using the cytokinesis block micronucleus (CBMN) assay. The radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼95%) and high stability in biological media. Hydrodynamic properties of the radiolabeled NPs remain stable after dual labeling. The interaction of SFN with blood elicits a mild host response, as expected. Furthermore, CBMN assay did not show genotoxicity induced by [99mTc]Tc-FITC-SFN under the described conditions. In conclusion, a feasible and robust dual-labeling method has been developed whose applicability has been demonstrated in vitro, showing its value for further investigations of silk fibroin NPs biodistribution in vivo. [ABSTRACT FROM AUTHOR]

With the objective to develop a potential 99mTc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with 99mTc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture. All complexes exhibited considerable uptake in AR-positive cells, which could be blocked by an excess of flutamide. The efflux from the cells was moderate. They also showed significantly lower uptakes in AR-negative cells, indicating interactions with the AR receptor. However, the binding affinities were considerably reduced by the coordination to 99mTc, and the complex that exhibited the best biological behavior did not show sufficient specificity towards AR-positive cells. [ABSTRACT FROM AUTHOR]

Background: Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. Methods: A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. Results: Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P < 0.01). Among the 36 primary lesions in the 34 patients, when IHC (2 +) or IHC (3 +) was used as the positive evaluation criterion, 99mTc-HP-Ark2 SPECT/CT imaging with a tumor-to-background ratio of 1.44 as the cutoff value reflected the HER2 status with sensitivity of 89.5% (17/19), specificity of 88.2% (15/17) and accuracy of 88.9% (32/36), while the 18F-FDG PET/CT showed sensitivity of 78.9% (15/19), specificity of 70.6% (12/17) and accuracy of 75.0% (27/36). In particular, 100% of IHC (3 +) tumors were all identified by 99mTc-HP-Ark2 SPECT/CT imaging. Conclusion: 99mTc-HP-Ark2 SPECT/CT can provide a specific, noninvasive evaluation of HER2 expression in breast cancer, showing great potential to guide HER2-targeted therapies in clinical practice. ClinicalTrials.gov Trial registration: NCT04267900. Registered 11th February 2020. Retrospectively registered, https://www.clinicaltrials.gov/ct2/results?pg=1&load=cart&id=NCT04267900. [ABSTRACT FROM AUTHOR]

As the decay daughter of 99Mo, 99mTc is the most widely used radioisotope in the field of nuclear medicine. Recently, the major 99Mo production reactors in the world are facing problems such as unplanned maintenance, shutdown and decommission, resulting in the unstable supply of 99Mo. Therefore, many developed countries have been actively exploiting alternative technologies for 99Mo production. In this paper, various 99Mo-production technologies by particle accelerator instead of reactor were introduced, and the research progress of producing 99Mo based on electron accelerator was summarized at home and abroad. The accelerator performance index and the key technologies in the production process were discussed in detail, such as the design of irradiation device and target, separation of 99mTc, recovery of 100Mo and waste management. In addition, some suggestions were put forward for the basic and applied research of relevant technologies in China and the commercialization of 99Mo production by electron accelerator.

The main objective of the present publication was to assess the reduction of internal radioactive contamination with 99mTc among medical personnel of nuclear medicine facilities using generally available respiratory tract protection systems. During the current research project, four respiratory tract protection systems were tested by estimation of 99mTc activity levels in blood samples collected from medical personnel. Medical staff were equipped with a disposable surgical mask, a half mask with gas absorbers, a half mask with aerosol absorbers and a half mask with gas absorbers with added Petryanov filter. The presented results indicate that wearing only a disposable surgical mask may significantly reduce radioactive internal contamination among medical personnel and improve their safety in the workplace. The best results of reduced 99mTc concentration in the blood were achieved by the use of a half mask with gas absorbers with added Pertryanov filters and a half mask with aerosol absorbers, where the reduction factors were estimated at 90% and 80%, respectively. Respiratory tract protection systems should become standard equipment for medical personnel performing ventilation–perfusion SPECT lung scans. [ABSTRACT FROM AUTHOR]

We hypothesized that a novel design of the LTVPWY (LY) peptide might exhibit a great potential for improving binding affinity and targeting HER2-overexpressed tumors. Hence, new dimer construction of 99mTc-labeled LY [99mTc-HYNIC-E(SSSLTVPWY)2] (99mTc-DLY) was introduced. Afterward, a head-to-head comparison of in vitro and in vivo experiments was performed between 99mTc-DLY and 99mTc-HYNIC-SSSLTVPWY as the monomer analog. The blocking dosage of trastuzumab reduced the uptake of the dimer about 20% more efficiently than the monomer in the SKOV-3 cell line. A twofold increase in competitive binding affinity and biological half-life was observed for 99mTc-DLY. The ovarian-tumor-bearing mice were detected with high contrast where the tumor-to-muscle ratio of 99mTc-DLY was notably increased about 40% using a gamma camera. The biodistribution experiment revealed an approximately 10% enhancement in tumor/blood, tumor/muscle, and tumor/bone ratios for the dimer. More rapid blood clearance was another achievement of the homodimer design. Overall, 99mTc-DLY successfully affected the pharmacokinetics and consequently the visualization of HER2-overexpressing tumors. [ABSTRACT FROM AUTHOR]

One of the innovative methods in cancer treatment with fewer side effects is the use of active principles produced by animals and microorganisms to generate new drugs with diagnosis and treatment capability for cancer. Androctonus crassicauda scorpion venom has high potential as an anti-tumor agent and has the ability to interfere with human physiology but is still unknown. Therefore, labeling venom with radionuclides is very important to study the biological distribution of toxins for diagnostic and therapeutic purposes of various diseases, especially cancer. In this research, the toxic fraction of this venom was labeled with 99mTc. The radiochemical purity of the labeled toxic fraction was obtained by using chromatographic systems. Animal biodistribution studies were performed after injecting the labeled compound into normal rats and 4T1 breast cancer-bearing mice. The radiochemical purity of 90% was obtained for labeled compound. Biological distribution studies showed relatively rapid clearance of the labeled compound from the blood circulation system. The accumulation of the labeled compound in the liver and kidney was the highest among the organs, which could indicate the possibility of toxin excretion metabolism from liver and the kidneys. The accumulation rate of the labeled compound after 15 min was 7% in the breast cancer mass, and the ratio of the distribution of the labeled compound in the breast cancer mass to the blood was 155% at 15 min post injection. The study results indicated that scorpion venom labeling with 99mTc could be a useful tool for the biodistribution and kinetic studies of the venoms for clinical use. On the other hand, based on the results of the biological distribution of the labeled compound in tumor-bearing mice, the 99mTc-venom complex can be used as an imaging agent to diagnose breast cancer. Moreover at the same time, with some measures, it can be used as a therapeutic agent for breast cancer with more consideration. We hope that the results of this study will be a step in the future for the clinical diagnostic and therapeutic purposes of cancer using natural products. [ABSTRACT FROM AUTHOR]

Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [99mTc]Tc-(HE)3-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)3), provided clear imaging of HER2 expressing breast cancer 2–4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G3C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)3-linker (designated as G3-(G3S)3C) would further improve the contrast of imaging using 99mTc-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9–5 nM. Biodistribution of [99mTc]Tc-G3-G3C, [99mTc]Tc-G3-(G3S)3C, and [99mTc]Tc-G3-E3C in mice was compared with the biodistribution of [99mTc]Tc-(HE)3-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-(HE)3-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications. [ABSTRACT FROM AUTHOR]

Purpose: The assessment of HER2 expression has a significant impact on optimizing cancer treatment protocol in patients. The aim of this study was to evaluate the potential usefulness of 99mTc-HYNIC-(Ser)3-LTVPWY peptide for detecting HER2 alteration after paclitaxel therapy of ovarian tumor xenografts in nude mice. Materials and Methods: Mice bearing SKOV-3 tumors were treated with paclitaxel and saline. The antitumor efficacy of paclitaxel was compared with the control group in tumor size and histopathological examinations. In biodistribution and imaging studies, the tumor uptakes of radiolabeled peptide were evaluated in mice-bearing ovarian tumors in both groups. The HER2 expressions in transplanted tumors were analyzed by immunohistochemistry (IHC). Results: Tumor size gradually increased in all mice during the treatment, whereas tumors had considerably faster growth in the saline group compared to those in the paclitaxel-treated mice. Paclitaxel could suppress ovarian tumor growth and prevent vascular and cell proliferation in the tumoral mass. Biodistribution and imaging results demonstrated nonsignificant radionuclide accumulations in transplanted tumors in the paclitaxel- and saline-treated groups. IHC staining confirmed the HER2 status that was similar in both groups. Conclusions: The response of HER2 status to paclitaxel in mice bearing HER2-expression tumors was profitably monitored by HER2 targeted 99mTc-HYNIC-(Ser)3-LTVPWY peptide that was agreement with IHC. The utilization of this radiolabeled peptide may be a valuable probe in evaluating HER2 status after chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we designed a new linear 6-Hydrazinonicotinamide (HYNIC)-conjugated peptide (HYNIC-KRWrNM) (M-6) and labeled with technetium-99m for gamma imaging of glioblastoma as a αvβ3-positive tumor. We evaluated tumor targeting ability of this radio-peptide and compared with previous 99mTc-labeled HYNIC-conjugated RGD analogue peptides. Procedures. One new linear peptide (HYNIC-KRWrNM) (M-6) was designed and labeled with technetium-99m in the presence of 2-[[1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl] amino] acetic acid (Tricine)/Ethylenediamine-N,N′-diacetic acid (EDDA) as co-ligand system. Then, this 99mTc-labeled peptide ([99mTc]Tc-M-7) was evaluated for in vitro stability in saline and serum, specific binding assay, internalization, and binding affinity (Kd). In addition, we performed biodistribution study and planar imaging on nude mice bearing U87-MG xenograft as a αvβ3-positive tumor. Results: The radiochemical yield of [99mTc]Tc-M-7 was obtained ˃95%. This 99mTc-labeled peptide remained stable and intact in saline solution after 24 h incubation. In addition, metabolic stability of this 99mTc-labeled peptide was obtained ˃60% after 4 h incubation in serum. The Kd value for [99mTc]Tc-M-7 was obtained 5.2 ± 1.0 nM. Based on biodistribution results in nude mice bearing U87-MG xenograft, tumor/muscle activity ratio was 6.22 and decreased to 1.89 in blocking group at the same time point (4 h p.i.). The blocking experiment results also indicated that tumor uptake and kidney uptake were αvβ3-mediated. In comparison with previous HYNIC-conjugated RGD analogue peptides, kidneys had the highest uptake of this 99mTc-labeled peptide (52.29 ± 11.48 at 1.5 h p.i. and 27.04 ± 0.66%ID/g at 4 h p.i.). Finally, similar to previous 99mTc-labeled HYNIC-conjugated RGD analogue peptides, [99mTc]Tc-M-7 showed acceptable tumor uptake after 4 h post-injection (based on ROI technique, target-to-background activity ratio = 3.80). Conclusions: This small linear 99mTc-labeled peptide, with high affinity to αvβ3 integrin, desirable water solubility, and cost efficient, demonstrates a potent tumor targeting ability as well as previous HYNIC-conjugated RGD analogue peptides. Hence, [99mTc]Tc-M-7 can be of service to as a new candidate for early detection of αvβ3-positive tumors. [ABSTRACT FROM AUTHOR]

Objective: The in vivo imaging of programmed death ligand 1 (PD-L1) can monitor changes in PD-L1 expression and guide programmed death 1 (PD-1) or PD-L1-targeted immune checkpoint therapy. A 99mTc-labeled affibody molecular probe targeting the PD-L1 receptor was prepared and evaluated its tracing effect in PD-L1-overexpressing colon cancer. Methods: The PD-L1 affibody was prepared by genetic recombineering. The 99mTc labeling of the affibody was achieved by sodium glucoheptonate and an SnCl2 labeling system. The labeling rate, radiochemical purity, and stability in vitro were determined by instant thin-layer chromatography; MC38-B7H1 (PDL1-positive) and MC38 (PD-L1-negative) colon cancer cells were used to evaluate its affinity to PD-L1 by cell-binding experiments. The biodistribution of the 99mTc-labeled affibody molecular probe was then determined in C57BL/6J mice bearing MC38-B7H1 tumors, and tumor targeting was assessed in C57BL/6J mice with MC38-B7H1, MC38 double xenografts. Result: The nondecayed corrected yield of the 99mTc-PD-L1 affibody molecular probe was 95.95% ± 1.26%, and showed good stability both in phosphate-buffered saline (PBS) and fetal bovine serum within 6 h. The affinity of the 99mTc-PD-L1 affibody molecular probe for cell-binding assays was 10.02 nmol/L. Single photon emission--computed tomography imaging showed a rapid uptake of the tracer in PD-L1-positive tumors and very little tracer retention in PD-L1-negative control tumors. The tracer was significantly retained in the kidneys and bladder, suggesting that it is mainly excreted through the urinary system. Heart, liver, lung, and muscle tissue showed no significant radioactive retention. The biodistribution in vitro also showed significant renal retention, a small amount of uptake in the thyroid and gastrointestinal tract, and rapid blood clearance, and the tumor-to-blood radioactivity uptake ratio peaked 120 min after drug injection. Conclusion: The 99mTc-PD-L1 affibody molecular probe that we prepared can effectively target to PD-L1-positive tumors imaging in vivo, and clear in blood quickly, with no obvious toxic side effects, which is expected to become a new type of tracer for detecting PD-L1 expression in tumors. [ABSTRACT FROM AUTHOR]