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A very new and highly specialized category of radiotracers that is still growing is radiolabeled peptides. Radiolabeled peptides, or radiopeptides, are powerful elements for diagnostic imaging and radionuclide therapy. These laboratory-manufactured peptides have gained attention due to their unique properties. The tiny structure of these peptides compared to proteins and antibodies makes them favorable regarding their availability through simple synthesis from amino acids, easy uptake by receptors on cancer cells, and high specificity and affinity for high-quality and accurate radio imaging. This study highlighted the potential of technetium-99m-labeled peptides in advancing diagnostic capabilities in directed research in Latin America.

Purpose: This study aims to evaluate the performance of dual-energy window (DEW) and triple-energy window (TEW) scatter correction methods in cardiac SPECT imaging with technetium-99m (Tc-99m) and thallium-201 (Tl-201) radioisotopes. Materials and Methods: The SIMIND Monte Carlo program was used to simulate the imaging system and produce the required projections. Two phantoms, including the simple cardiac phantom and the NCAT phantom, were used to evaluate the scatter correction methods. The simulations were repeated 5 times for each phantom and finally, the mean values obtained from these 5 tests were used in the analysis of the results. Results: The obtained results from this study show that in the case of both investigated phantoms, the use of correction methods leads to improve the contrast of the images obtained from Tc-99m and Tl-201 radioisotopes. In the case of the simple cardiac phantom, the use of DEW and TEW correction methods leads to a relative increase in image contrast of about 23.88% and 12.23% for 99mTc radioisotope and about 29.19% and 20.98% for 201Tl radioisotope, respectively. This relative increase in the case of the NCAT phantom is about 22.48% and 19.43% for 99mTc radioisotope and about 27.74% and 24.74% for 201Tl radioisotope, respectively. Conclusion: According to the obtained results, despite the higher contrast of the noncorrected images of 99mTc radioisotope, the relative increase in contrast of the corrected images of 201Tl radioisotope is more than that of 99mTc radioisotope. Furthermore, for both radioisotopes, the relative increase related to the DEW method is higher than the TEW method.

A Tc-99m thyroid scanning is one of the most common diagnostic modalities in nuclear medicine for the evaluation of various thyroid dysfunctions and anomalies. Therefore, this review study will delve into the various dimensions related to patient exposure during Tc-99m thyroid scanning. Various subjects are covered, such as radiation risks from the procedure, methods for reducing patient exposures, imaging technology developments, and the importance of an effective radiation safety program. In this review, some new developments in and possible ways toward better safety for the patient and diagnostic accuracy of the thyroid imaging methods are also discussed.

Abstract Background Personalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose–effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom. Results Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6–10.1%). A standardised protocol did not improve variation (interquartile range 8.4–9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5–0.7 and 0.6–0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6–0.7). Conclusion Eliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy.

Background/Objectives: Dithiocarbazates (DTCs) and their metal complexes have been studied regarding their property as anticancer activities. In this work, using S-benzyl-5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pirazol-1-carbodithionate (H2bdtc), we prepared [ReO(bdtc)(Hbdtc)] and [[99mTc]TcO(bdtc)(Hbdtc)] complexes for tumor uptake and animal biodistribution studies. Methods: Re complex was prepared by a reaction of H2bdtc and (NBu4)[ReOCl4], the final product was characterized by IR, 1H NMR, CHN, and MS-ESI. 99mTc complex was prepared by the reaction of H2bdtc and [[99mTc]TcO4− and analyzed by planar and HPLC radiochromatography, and the stability was evaluated against amino acids and plasma. Biodistribution was performed in C57B/6 mice with B16F10 and TM1M implanted tumor. Results: Re is asymmetric coordinated by two dithiocarbazate ligands, one with O,N,S chelation, and the other with N,S chelation; [[99mTc]TcO(bdtc)(Hbdtc)] was prepared with a radiochemical yield of around 93%. The radioactive complex is hydrophobic (LogP = 1.03), stable for 6 h in PBS and L-histidine solution; stable for 1 h in plasma, but unstable in the presence of L-cysteine. Ex vivo biodistribution demonstrated that the compound has a fast and persistent (until 2 h) uptake by the spleen (55.46%), and tumor B16F10 and TM1M uptake is lower than 1%. In vivo SPECT/CT imaging confirmed ex vivo biodistribution, except by heterogenous TM1M accumulation but not in the B16-F10 lineage. Conclusions: H2bdtc proved to be an interesting chelator for rhenium or [99mTc]technetium. The right spleen uptake opened the opportunity to deepen the study of the molecule in this tissue and justifies future studies to identify the reason of heterogenous uptake in TM1M tumor uptake.

The use of radiopharmaceuticals for diagnostics in oncology allows for the detection of the disease at an early stage. Among diagnostic radionuclides, 99mTc is a promising isotope that has been used to create several drugs for clinical use. One of the most effective 99mTc chelators is 6-hydrazinylnicotinic acid (HYNIC), which, when combined with various vector molecules, can be used for targeted delivery of radionuclides to tumor tissues. At the same time, it is known that tetrapyrrole macrocycles are capable of selective accumulation in tumors, and thus can be used to target radiopharmaceuticals with 99mTc. In this work, the conjugate of natural chlorin and HYNIC was obtained, and preliminary preclinical studies were carried out on its radiocomplex with 99mTc.

This systematic review and meta-analysis protocol aims to evaluate the comparative efficacy of different sentinel lymph node (SLN) detection techniques in the management of vulvar cancer. Vulvar cancer, though rare, predominantly affects older women and requires effective management strategies. The SLN technique has become a standard approach for early-stage cases, offering reduced morbidity compared to complete lymphadenectomy. Currently, various SLN detection methods exist, including the use of Technetium-99m (Tc99m), Indocyanine Green (ICG), and superparamagnetic iron oxide (SPIO), but there is a lack of comprehensive comparison of their efficacy. This review will systematically search relevant databases, including PubMed, Scopus, Cochrane, Web of Science and Embase following PRISMA guidelines, to gather data from clinical trials. The primary outcome will be the detection rates of SLN techniques with secondary outcomes examining patient characteristics and procedural factors. The analysis will utilize random-effects models to compare detection rates across studies. The results of this study aim to provide insights into the optimal SLN detection method with potential implications for clinical practice guidelines in vulvar cancer management. The protocol is registered under the PROSPERO registration number CRD42024590774.

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (99mTc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99mTc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh2), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99mTc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97–98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD7.4 values (1.6–2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac-[99mTc(CO)3(Cip-DTC)(PPh3)] (2′) showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac-[99mTc(CO)3(Cip-DTC)(TMPP)] (3′) demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99mTc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals.

Abstract Background Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit. First, the radiolabeling of O-TRENOX and O-TRENSOX with 99mTc was investigated. Different parameters such as the quantity of chelating agent, type of reducing agent, pH and temperature of the reaction mixture were adjusted in order to find the best radiolabeling conditions. Then an assessment of the partition coefficient by measuring the distribution of each radiosynthesized complex between octanol and phosphate-buffered saline was realized. The complex’s charge was evaluated on three different celluloses (neutral, negatively charged P81 and positively charged DE81), and finally in vivo studies with biodistribution and SPECT imaging of [99mTc]Tc-O-TRENOX and [99mTc]Tc-O-TRENSOX were performed. Results The radiolabeling studies showed a rapid and efficient complexation of 99mTc with both chelating agents. Using tin pyrophosphate as the reducing agent and a minimum of 100 nmol of ligand, we obtained the [99mTc]Tc-O-TRENOX complex with a radiochemical purity of more than 98% and the [99mTc]Tc-O-TRENSOX complex with one above 97% at room temperature within 5 min. [99mTc]Tc-O-TRENOX complex was lipophilic and neutral, leading to a hepatobiliary elimination in mice. On the contrary, the [99mTc]Tc-O-TRENSOX complex was found to be hydrophilic and negatively charged. This was confirmed by a predominantly renal elimination in mice. Conclusions These encouraging results allow us to consider the O-TRENOX/99mTc and O-TRENSOX/99mTc complexes as serious candidates for SPECT imaging chelators. This study should be continued by conjugating these tris-oxine ligands to peptides or antibodies and comparing them with the other bifunctional agents used with Tc.

To develop a low bladder accumulation SPECT prostate cancer imaging agent, 99mTc-P137 was prepared on the basis of 68Ga-P137 structure, and the probe was subjected to detailed preclinical evaluation and preliminary clinical translation studies. The labeled precursor HYNIC-P137 was prepared by solid-phase synthesis method, and the labeled precursor 99mTc was labeled with EDDA as co-ligand, and the product 99mTc-P137 was quality controlled. The lipid-water partition coefficient and in vitro stability of 99mTc-P137 were examined, and its uptake and inhibition on PSMA-positive and negative cells were investigated. Biodistribution in normal Kunming mice and SPECT/CT imaging in hormonal mice were performed, and finally, clinical translation studies were performed. The results showed that the precursor HYNIC-P137 could be easily obtained from solid-phase synthesis, and the labeled product 99mTc-P137 had a radiochemical purity close to 100%, good in vitro stability and high hydrophilicity. Normal Kunming mouse biodistribution showed rapid blood clearance of this probe, which was mainly metabolized by the kidney. MicroSPECT/CT of tumor-bearing mice showed that 99mTc-P137 was concentrated mainly in PSMA-positive tumors and renal regions, and both could be significantly inhibited, showing a high degree of intra-specific specificity. Clinical translation showed low accumulation of 99mTc-P137 in the bladder, high intrahepatic radioactivity, and good detection performance for prostate cancer foci in situ and lymph node metastases. It was shown that 99mTc-P137 with high affinity and low bladder accumulation is a novel ODAP-based SPECT prostate cancer imaging probe.

In the present study, the aim is to synthesize and introduce the combination of methoxy amido xanthate MAX and then label it with 99mTc radionuclide as a novel diagnostic agent for single-photon computed tomography (SPECT) imaging. A chelator-designed ligand was synthesized from a blend of chloroacetamide and xanthate in certain proportions. After that MAX ligand labeling process was performed by directly milking 99mTc from the generator (99Mo / 99mTc). Thus, tin chloride was employed as a reducing agent, and the effect of parameters such as additives like ascorbic acid, changing the concentration of the cheating agent, and pH were evaluated to optimize the labeling conditions. The product was then identified by infrared spectroscopy (FTIR) and magnetic resonance imaging (NMR). Labeling of the complex at laboratory temperature was determined to be 93%. The new 99mTc-MAX radiopharmaceutical with a radionuclide and radiochemical purity of over 90% can be used as an encouraging diagnostic agent in clinics and preclinical studies, which will be addressed in future studies.

Scintigraphy and Positron Emission Tomography (PET) are both nuclear medicine imaging techniques, providing functional information of the imaged areas. Scintigraphy is a two-dimensional projected imaging technique that was introduced in equine imaging in the late 1970s. Scintigraphy allows imaging of large body parts and can cover multiple areas, remaining the only technique commonly used in horses for whole body imaging. PET is a cross-sectional imaging technique, first used in horses in 2015, allowing higher resolution three-dimensional functional imaging of the equine distal limb. This manuscript will cover current use and values of these two modalities in equine lameness diagnosis.

With the development of PD-1/PD-L1 immune checkpoint inhibitor therapy, the ability to monitor PD-L1 expression in the tumor microenvironment is important for guiding therapy. This study was performed to develop a novel radiotracer with optimal pharmacokinetic properties to reflect PD-L1 expression in vivo via single-photon emission computed tomography (SPECT) imaging. [99mTc]Tc-HYNIC-WL12-tricine/M (M = TPPTS, PDA, ISONIC, 4-PSA) complexes with high radiochemical purity (>97%) and suitable molar activity (from 100.5 GBq/μmol to 300 GBq/μmol) were prepared through a kit preparation process. All 99mTc-labeled HYNIC-WL12 radiotracers displayed good in vitro stability for 4 h. The affinity and specificity of the four radiotracers for PD-L1 were demonstrated both in vitro and in vivo. The results of biodistribution studies displayed that the pharmacokinetics of the 99mTc-HYNIC-conjugated radiotracers were significantly influenced by the coligands of the radiotracers. Among them, [99mTc]Tc-HYNIC-WL12-tricine/ISONIC exhibited the optimal pharmacokinetic properties (t1/2α = 8.55 min, t1/2β = 54.05 min), including the fastest clearance in nontarget tissues, highest tumor-to-background contrast (e.g., tumor-to-muscle ratio, tumor-to-blood ratio: 40.42 ± 1.59, 14.72 ± 2.77 at 4 h p.i., respectively), and the lowest estimated radiation absorbed dose, highlighting its potential as a clinical SPECT imaging probe for tumor PD-L1 detection.

This study presents the synthesis and characterization of chitosan-glutamine-based biocompatible nanoparticles (nano-conjugate) as a platform for developing an efficient nano-radiopharmaceutical agent for liver imaging. The nanoparticles were labeled with technetium-99 m, resulting in the formation of 99mTc-chitosan-glutamine. Various characterization techniques, including furrier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR) were performed for confirmation of synthesized nano-conjugate. Scanning electron microscopy (SEM), dynamic light scattering (DLS), and static light scattering (SLS) spectroscopies were employed to investigate the particle properties such as size, zeta potential, and molecular weight. MTT assay was conducted to study the toxicity of chitosan-glutamine showing that nano-conjugate had a toxicity on cancer cell in-vitro. In-vivo studies were conducted by administering 99mTc-chitosan-glutamine to mice, followed by whole body SPECT imaging. The imaging process was performed at three different time points post-injection: 15, 60, and 120 min. The SPECT results revealed a significantly accumulation in the liver. Also, biodistribution study showed that accumulation in liver (% ID/g = 23.15%) was significantly higher than other organs. Our in-vitro and in-vivo findings suggest that 99mTc-chitosan-glutamine could serve as a theranostic agent for cancer imaging using SPECT technology.

Abstract Background Radioguided surgery (RGS) has recently emerged as a valuable new tool in the management of recurrent prostate cancer (PCa). After preoperative injection of a 99mTc-labeled prostate-specific membrane antigen (PSMA) inhibitor, radioguided intraoperative identification and resection of lesions is facilitated by means of suitable γ-probes. First clinical experiences show the feasibility of RGS and suggest superiority over conventional lymph node dissection in recurrent PCa. However, commonly used [99mTc]Tc-PSMA-I&S exhibits slow whole-body clearance, thus hampering optimal tumor-to-background ratios (TBR) during surgery. We therefore aimed to develop novel 99mTc-labeled, PSMA-targeted radioligands with optimized pharmacokinetic profile to increase TBR at the time of surgery. Methods Three 99mTc-labeled N4-PSMA ligands were preclinically evaluated and compared to [99mTc]Tc-PSMA-I&S. PSMA affinity (IC50) and internalization were determined on LNCaP cells. Lipophilicity was assessed by means of the distribution coefficient logD 7.4 and an ultrafiltration method was used to determine binding to human plasma proteins. Biodistribution studies and static µSPECT/CT-imaging were performed at 6 h p.i. on LNCaP tumor-bearing CB17-SCID mice. Results The novel N4-PSMA tracers were readily labeled with [99mTc]TcO4 − with RCP > 95%. Comparable and high PSMA affinity was observed for all [99mTc]Tc-N4-PSMA-ligands. The ligands showed variable binding to human plasma and medium to low lipophilicity (logD 7.4 − 2.6 to − 3.4), both consistently decreased compared to [99mTc]Tc-PSMA-I&S. Biodistribution studies revealed comparable tumor uptake among all [99mTc]Tc-N4-PSMA-ligands and [99mTc]Tc-PSMA-I&S, while clearance from most organs was superior for the novel tracers. Accordingly, increased TBR were achieved. [99mTc]Tc-N4-PSMA-12 showed higher TBR than [99mTc]Tc-PSMA-I&S for blood and all evaluated tissue. In addition, a procedure suitable for routine clinical production of [99mTc]Tc-N4-PSMA-12 was established. Labeling with 553 ± 187 MBq was achieved with RCP of 98.5 ± 0.6% (n = 10). Conclusion High tumor accumulation and favorable clearance from blood and non-target tissue make [99mTc]Tc-N4-PSMA-12 an attractive tracer for RGS, possibly superior to currently established [99mTc]Tc-PSMA-I&S. Its GMP-production according to a method presented here and first clinical investigations with this novel radioligand is highly recommended.

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be −2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

Gold nanoparticles (AuNPs) radiolabeled with therapeutic and diagnostic radioisotopes have been broadly studied as a promising platform for early diagnosis and treatment of many diseases including cancer. Our main goal for this study was the comparison of the biodistribution profiles of four different concentrations of gold nanoconjugates radiolabeled with Technetium-99m (99mTc). More specifically, AuNPs with an average diameter of 2 nm were functionalized with a tridentate thiol ligand. Four different concentrations were radiolabeled with 99mTc-tricarbonyls with high radiolabeling yields (>85%) and were further purified, leading to radiochemical purity of >95%. In vitro stability of the radiolabeled nanoconstructs was examined in cysteine and histidine solutions as well as in human serum, exhibiting robust radiolabeling up to 24 h post-preparation. Moreover, in vitro cytotoxicity studies were carried out in 4T1 murine mammary cancer cells. In vivo tracking of the radiolabeled nanoconjugates at both concentrations was examined in normal mice in order to examine the effect of AuNPs’ concentration on their in vivo kinetics. Our work demonstrates that varying concentrations of radiolabeled AuNPs lead to notably different biodistribution profiles.

Due to its small size and high affinity binding, the engineered scaffold protein ADAPT6 is a promising targeting probe for radionuclide imaging of human epidermal growth factor receptor type 2 (HER2). In a Phase I clinical trial, [99mTc]Tc-ADAPT6 demonstrated safety, tolerability and capacity to visualize HER2 expression in primary breast cancer. In this study, we aimed to select the optimal parameters for distinguishing between breast cancers with high and low expression of HER2 using [99mTc]Tc-ADAPT6 in a planned Phase II study. HER2 expression was evaluated in primary tumours and metastatic axillary lymph nodes (mALNs). SPECT/CT imaging of twenty treatment-naive breast cancer patients was performed 2 h after injection of [99mTc]Tc-ADAPT6. The imaging data were compared with the data concerning HER2 expression obtained by immunohistochemical evaluation of samples obtained by core biopsy. Maximum Standard Uptake Values (SUVmax) afforded the best performance for both primary tumours and mALNs (areas under the receiver operating characteristic curve (ROC AUC) of 1.0 and 0.97, respectively). Lesion-to-spleen ratios provided somewhat lower performance. However, the ROC AUCs were still over 0.90 for both primary tumours and mALNs. Thus, lesion-to-spleen ratios should be further evaluated to find if these could be applied to imaging using stand-alone SPECT cameras that do not permit SUV calculations.

The aim of the study was to evaluate the feasibility of using single-photon emission computed tomography (SPECT) with [99mTc]Tc-1-THIO-D-glucose in the detection of brain tumor malignancy. Material and methods. The study included 70 patients diagnosed with grade II–Iv malignant brain tumors and 10 patients with benign brain tumors. The control group consisted of 20 patients who had no pathological changes in the brain at the time of diagnosis. All patients underwent single-photon emission computed tomography of the brain 40 minutes after intravenous injection of [99mTc]Tc-1-THIO-D-glucose at a dose of 500 MBq. The [[99mTc]Tc-1-THIO-D-glucose radiopharmaceutical was prepared directly in the nuclear medicine department in strict accordance with the instructions. The head and neck of the patient fell into the field of view of the detectors of the gamma camera, 32 projections were recorded in a matrix of 256×256 pixels without hardware magnification. High-resolution low-energy collimators were used. Results. In patients with verified diagnosis of malignant brain tumors, SPECT with [99mTc]Tc-1-THIO-D-glucose correctly visualized tumors in all cases. The tumor was visualized as a zone of increased accumulation of [99mTc]Tc-1-THIO-D-glucose of varying intensity and size. However, benign brain lesions did not show [99mTc]Tc-1-THIO-D-glucose uptake. Physiological accumulation of [99mTc]Tc-1-THIO-D-glucose was observed in soft tissues of the aponeurotic helmet, the choroid of the brain, the mucous membranes of the nasal cavity, and the sinuses of the skull bones. Pathological changes in the brain revealed by SPECT were confirmed by MRI with contrast enhancement. Conclusion. The study demonstrated a high efficiency of SPECT with [99mTc]Tc-1-THIO-D-glucose in visualization of malignant brain tumors. The sensitivity, specificity and accuracy of SPECT with [99mTc]Tc-1-THIO-D-glucose in the imaging of malignant brain tumors were 93–100 %, 65–100 %, 95–100 %, respectively. The data obtained suggest that [99mTc]Tc-1-THIO-D-glucose SPECT as an additional method for the detection of malignant brain tumors can increase access to radionuclides for this group of patients and improve the quality of cancer care.

Background: Estimation of the thyroid gland volume is generally considered important in several pathologic situations. The main objective of this study was to evaluate the thyroid uptake (TU) of 99mTcO4- in Sudanese people, using gamma camera and dose calibrator methods and comparing the results with international TU levels. Methods and Results: The study was conducted in 2020 at the National Cancer Institute (Wad Madani state, University of Gezira, Sudan). This study included 64 patients (58 females and 6 males) aged 13-81 years (37.25±14.58 years) with normal TU. Most patients (43.8%) were in the age subgroup of 31-48 years, followed by 39.1% in the age subgroup of 13-30 years.Two calibration methods were used to calculate full and empty syringes before and after radiopharmaceutical injection: a) using a dose calibrator measuring in MBq; b) with gamma camera images of the full and empty syringes for 1 minute (counts). In the dose calibrator, the activity and time of a 99mTc point source in a syringe were monitored, the point source was precisely aligned with the center of the camera, and a static image was obtained with static parameters at a distance of 5cm and 7cm between source and pinhole collimator (265×265 matrix). The study showed that the TU values using the dose calibrator method were more consistent with radiation protection principles of minimizing the exposure to radiation for staff. The method also had higher values than those measured with a gamma camera due to the scatter radiation. The relationship between TU of 99mTcO4- with syringe measured by dose calibrator and gamma camera at a distance of 5cm and 7cm, given a coefficient of determination (R2) of 0.9937 and 0.9591, respectively Conclusion: There was no big change in the TU between the two methods, especially at 5cm object-to-pinhole distance, where it gave the best result for optimum imaging in the 99mTcO4- TU test.

Abstract Background Anthropomorphic torso phantoms, including a cardiac insert, are frequently used to investigate the imaging performance of SPECT and PET systems. These phantom solutions are generally featuring a simple anatomical representation of the heart. 3D printing technology paves the way to create cardiac phantoms with more complex volume definition. This study aimed to describe how a fillable left ventricular myocardium (LVm) phantom can be manufactured using geometry extracted from a patient image. Methods The LVm of a healthy subject was segmented from 18F-FDG attenuation corrected PET image set. Two types of phantoms were created and 3D printed using polyethylene terephthalate glycol (PETG) material: one representing the original healthy LVm, and the other mimicking myocardium with a perfusion defect. The accuracy of the LVm phantom production was investigated by high-resolution CT scanning of 3 identical replicas. 99mTc SPECT acquisitions using local cardiac protocol were performed, without additional scattering media (“in air” measurements) for both phantom types. Furthermore, the healthy LVm phantom was inserted in the commercially available DataSpectrum Anthropomorphic Torso Phantom (“in torso” measurement) and measured with hot background and hot liver insert. Results Phantoms were easy to fill without any air-bubbles or leakage, were found to be reproducible and fully compatible with the torso phantom. Seventeen segments polar map analysis of the "in air” measurements revealed that a significant deficit in the distribution appeared where it was expected. 59% of polar map segments had less than 5% deviation for the "in torso” and "in air” measurement comparison. Excluding the deficit area, neither comparison had more than a 12.4% deviation. All the three polar maps showed similar apex and apical region values for all configurations. Conclusions Fillable anthropomorphic 3D printed phantom of LVm can be produced with high precision and reproducibility. The 3D printed LVm phantoms were found to be suitable for SPECT image quality tests during different imaging scenarios. The flexibility of the 3D printing process presented in this study provides scalable and anthropomorphic image quality phantoms in nuclear cardiology imaging.

A radiotracer investigation was carried out in a Thermal Stratification Test Facility (TSTF) with objectives of investigating the dispersion and diffusion of radionuclide and effectiveness of the thermocline to minimize the radionuclide content in the hot water layer. Technetium-99m (99mTc) as sodium pertechnetate was used as a radiotracer in the investigation. Qualitative analysis showed that a thermocline is formed within the TSTF and is effective in preventing the transport of radionuclide from bottom section to the top section of the facility. It was found that the radiotracer injected at the bottom of the pool took about 17.4 h to disperse from bottom to the top of the facility. The results of the investigation helped in understanding the effectiveness of hot water layer and thus to minimize the pool top radiation levels.

Abstract Background Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics. Results Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article. Conclusion Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment. Graphical abstract

This paper presents the application of ciprofloxacin as a biologically active molecule (vector) for delivering diagnostic radiopharmaceuticals to the sites of bacterial infection. Ciprofloxacin-based radioconjugates containing technetium-99m or gallium-68 radionuclides were synthesised, and their physicochemical (stability, lipophilicity) and biological (binding study to Staphylococcus aureus and Pseudomonas aeruginosa) properties were investigated. Both the tested radiopreparations met the requirements for radiopharmaceuticals, and technetium-99m-labelled ciprofloxacin turned out to be a good radiotracer for the tomography of diabetic foot syndrome using SPECT.

Recent cancer therapies have focused on reducing immune suppression in the tumor microenvironment to prevent cancer progression and metastasis. PD-1 is a checkpoint protein that stops the immune response and is expressed on immune T cells. Cancer cells express a PD-1 ligand (PD-L1) to bind to the T-cell surface and activate immunosuppressive pathways. This study aimed to design, synthesize, and evaluate a 99mTc-labeled PD-L1-targeting cyclic peptide inhibitor (99mTc-iPD-L1) as a novel SPECT radiopharmaceutical for PD-L1 expression imaging. AutoDock software (version 1.5) was used to perform molecular docking for affinity calculations. The chemical synthesis was based on the coupling reaction of 6-hydrazinylpyridine-3-carboxylic acid with a 14-amino-acid cyclic peptide. iPD-L1 was prepared for 99mTc labeling. Radio-HPLC was used to verify radiochemical purity. The stability of the radiopeptide in human serum was evaluated by HPLC. iPD-L1 specificity was assessed by SDS-PAGE. [99mTc]Tc-iPD-L1 cellular uptake in PD-L1-positive cancer cells (HCC827 and HCT116) and biodistribution in mice with induced tumors were also performed. One patient with advanced plantar malignant melanoma received [99mTc]Tc-iPD-L1. The iPD-L1 ligand (AutoDock affinity: −6.7 kcal/mol), characterized by UPLC mass, FT-IR, and UV–Vis spectroscopy, was obtained with a chemical purity of 97%. The [99mTc]Tc-iPD-L1 was prepared with a radiochemical purity of >90%. In vitro and in vivo analyses demonstrated [99mTc]Tc-iPD-L1 stability (>90% at 24 h) in human serum, specific recognition for PD-L1, high uptake by the tumor (6.98 ± 0.89% ID/g at 1 h), and rapid hepatobiliary and kidney elimination. [99mTc]Tc-iPD-L1 successfully detected PD-L1-positive lesions in a patient with plantar malignant melanoma. The results obtained in this study warrant further dosimetric and clinical studies to determine the sensitivity and specificity of [99mTc]Tc-iPD-L1/SPECT for PD-L1 expression imaging.

Objective(s): Myocardial infarction caused by ischemia of heart tissue is the main reason for death worldwide; therefore, early detection can reduce mortality and treatment costs. Erythropoietin (EPO) has protection effects on ischemic tissue due to nonhematopoietic peptide (pHBSP; ARA-290) which is derived from the B-subunit of EPO. Materials and Methods: We designed and synthesized a modified DOTA-(Lys-Dabcyl6, Phe7)-ARA-290 using Fmoc solid-phase peptide synthesis strategies. To improve serum stability, Fmoc-Lys-(Dabcyl)-OH as lipophilic amino acid was synthesized along with Fmoc-Phe-OH which then were substituted with Arg6 and Ala7, respectively; they were then investigated for the ability to detect ischemic cardiac imaging. DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 was labeled with technetium 99m, and its radiochemical purity (RCP), stability in the presence of human serum and, specific bind to hypoxic H9c2 cells were evaluated. In vivo studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model. Results: Radiolabeling purity was obtained more than 96% by ITLC, and in vitro stability of the radiopeptide up to 6 hr was 85%. The binding of 99mTc-ARA-290 to hypoxic cells was remarkably higher than normoxic cells (3 times higher than normoxic cells at 1 hr). Biodistribution and SPECT imaging on the cardiac ischemic model showed that radiopeptide considerably accumulated in the ischemic region (cardiac ischemic-to-lung rate = 3.65 ID/g % at 0.5 hr).Conclusion: The results of studies, in vitro and in vivo, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia.

Nuclear medicine techniques allow important insights not only into oncologic, neurologic, and infectious conditions, but also for the assessment of rheumatic diseases. This review provides a brief, update on the potential role of nuclear imaging in rheumatology, especially on 18F-fluorodeoxyglucose (FDG) positron emission tomography for the diagnosis of giant cell arteritis and other large vessel arteritis according to international recommendations. Besides, the potential role of this and other nuclear imaging techniques for the rheumatologic practice are summarized. With 18F-fluoride as tracer for positron emission tomography, a new option for bone scintigraphy comes up, whereas the use of a semiquantitative sialoscintigraphy is no more supported for classification of Sjögren's syndrome according to current recommendations. Other techniques are used for different organ manifestations in systemic rheumatic diseases like for myocardial infarction and apoplectic insult.

Prostate-specific membrane antigen (PSMA) is a well-validated prostate cancer marker but reported PSMA-targeted tracers derived from the Lys-urea-Glu pharmacophore including the clinically validated [99mTc]Tc-EDDA/HYNIC-iPSMA have high off-target uptake in kidneys, spleen, and salivary glands. In this study, we synthesized and evaluated three novel 99mTc-labeled PSMA-targeted tracers and investigated if the tracers derived from the Lys-urea-Aad pharmacophore could have minimized uptake in off-target organs/tissues. In vitro competition binding assays showed that compared with HYNIC-iPSMA, the three novel ligands had slightly weaker PSMA binding affinity (average Ki = 3.11 vs. 8.96–11.6 nM). Imaging and ex vivo biodistribution studies in LNCaP tumor-bearing mice showed that [99mTc]Tc-EDDA/HYNIC-iPSMA and the three novel tracers successfully visualized LNCaP tumor xenografts in SPECT images and were excreted mainly via the renal pathway. The average tumor uptake at 1 h post-injection varied from 5.40 to 18.8%ID/g, and the tracers derived from the Lys-urea-Aad pharmacophore had much lower uptake in the spleen and salivary glands. Compared with the clinical tracer [99mTc]Tc-EDDA/HYNIC-iPSMA, the Lys-urea-Aad-derived [99mTc]Tc-EDDA-KL01127 had lower background uptake and superior tumor-to-background contrast ratios and is therefore promising for clinical translation to detect prostate cancer lesions with SPECT.

Low-energy electrons (Auger electrons) can be produced via the interaction of photons with gold atoms in gold nanorods (AuNRs). These electrons are similar to those emitted during the decay of technetium-99m (99mTc), a radioactive nuclide widely used for diagnostics in nuclear medicine. Auger and internal conversion (IC) electron emitters appropriately targeted to the DNA of tumors cells may, therefore, represent a new radiotherapeutic approach. 99mTc radiopharmaceuticals, which are used for diagnosis, could indeed be used in theragnostic fields when loaded on AuNRs and delivered to a tumor site. This work aims to provide a proof of concept (i) to evaluate AuNRs as carriers of 99mTc-based radiopharmaceuticals, and (ii) to evaluate the efficacy of Auger electrons emitted by photon-irradiated AuNRs in inducing radio-induced damage in T98G cells, thus mimicking the effect of Auger electrons emitted during the decay of 99mTc used in clinical settings. Data are presented on AuNRs’ chemical characterization (with an aspect ratio of 3.2 and Surface Plasmon Resonance bands at 520 and 680 nm) and the loading of pharmaceuticals (after 99mTc decay) on their surface. Spectroscopic characterizations, such as UV-Vis and synchrotron radiation-induced X-ray photoelectron (SR-XPS) spectroscopies, were performed to investigate the drug–AuNR interaction. Finally, preliminary radiobiological data on cell killing with AuNRs are presented.

Molybdenum-99 (99Mo) is the parent radioisotope of technetium-99m (99mTc),an essential medical radioisotope for diagnostic agents in nuclear medicine.In 99Mo/99mTc generator, a chromatography column system with 99Mo adsorbent as afiller is usually used to produce 99mTc in hospitals. However, it is still challenging to find high-performance adsorbentsfor Mo adsorption.We have synthesized both ordered and disordered mesoporous alumina and compared their performance as 99Mo adsorbents. These materials were prepared via a soft-templated method using a triblock copolymer as the template, followed by air calcination at 400°C.The amount of nitric acid (HNO3) and the drying time were adjusted systematically to synthesize the ordered mesoporous alumina. The obtained ordered and disordered mesoporous alumina were characterized by low-and wide-angle X-ray diffractions (XRD), nitrogen adsorption-desorption, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The 99Mo adsorption capacities of these materials were evaluated by using the batch method. The experimental results show that the ordered mesoporous alumina hasa higher 99Mo adsorption capacity of 72.06 mg(Mo)g-1 than the disordered mesoporous alumina (50.12 mg(Mo)g-1). The results indicate the excellent potential of ordered mesoporous alumina as an adsorbent for the 99Mo/99mTc generator column.

The aim of this study was to label quercetin as a natural flavonoid compound with technetium-99m and to study its biological distribution in different tissues of C57 mice bearing melanoma B16F10 cells for tumor diagnosis. Quercetin labeling was performed with technetium-99m at 1.5 mg quercetin and 40 μg SnCL2 at room temperature and pH about 5. Labeling yield was evaluated using TLC in acetone and water / acetonitrile as solvents. Also, in animal study, the tissue activity of various organs including heart, lung, stomach, intestine, liver, kidney, blood, spleen, muscle, and tumor were measured through gamma counter. Radiochemical purity above 95% and radiochemical stability of 90% at one hour were observed. The results of biological distribution of the labeled compound showed the highest radioactivity uptake in liver, kidney, intestine and tumor (2.2 ± 0.17 at 2 h post injection) tissues. Quercetin labeled through direct method with high radiochemical purity can be used as a candidate for diagnostic radiotracer.

Most important quality attributes of any radiopharmaceutical (RPh) are its radiochemical purity (RCP) or content of radiochemical impurities (RCIs) that have to comply with respective norms and limits. However, at present, there is no unified approach to validation of analytical methods in the context of highly radioactive samples.The aim of the study was to develop an approach to validation of methods for determination of RCI content in RPhs.Materials and methods: the authors determined the content of RCIs in a radiopharmaceutical formulation containing a complex of technetium-99m and methylenediphosphonic acid by the radiometric method after isolation of impurities from the main compound by thin-layer chromatography using silica gel and methyl ethyl ketone (for sodium pertechnetate determination) and silica gel and 13.6% sodium acetate solution (for determination of hydrolysed reduced technetium-99m). The radioactivity was registered by a chromatogram scanner with a detector of gamma-rays with energies from 0.05 to 1.5 MeV.Results: the paper analyses existing official approaches to validation of analytical procedures and compares them with the results of experimental studies described in available publications. It assesses the validation parameters for compliance with the acceptance criteria set forth in the current regulations and substantiates selectivity of chromatographic determination of impurities under the selected test conditions. Coefficients of variation for repeatability, reproducibility, and accuracy did not exceed 4.5, 2.8, and 8.9%, respectively, given the relative error of not more than 10.5%. The study demonstrated signal linearity for the 10-fold dilution of the standardised sodium pertechnetate solution, it also demonstrated correspondence between the applied and detected radioactivity when performing the test in the impurity content range of 0.5–5%. The validation procedure was associated with significant radiation burden for the personnel of the quality control laboratory.Conclusions: the authors suggested a methodological approach to validation of methods for determination of RCI content in technetium-99m-based RPhs. This approach may be used in the development of a guideline on validation of analytical methods for RCP/RCI determination in RPhs, or for introduction of relevant sections into existing documents.

Introduction. Skin cancers came first in Russia in numbers of oncological diseases. Melanoma, making up only a small part of these cases, leads to the most serious consequences. The nuclear medicine methods application is necessary at the stages of clarifying the diagnosis, searching for remote metastases and the treatment monitoring. The work is devoted to one of the stages of the radiopharmaceutical development for the diagnostics of malignant melanoma and its metastases based on the synthetic analog of α-melanocyte stimulating hormone (SAH) and radionuclide Tc-99m.Aim. The selection of optimal conditions for the preparation of the SAH ∙ 99mTc complex and the study of the using possibility it as a diagnostic tool in in vitro experiments.Materials and methods. Experimental work was carried out to optimize the conditions for obtaining the complex compound SAH ∙ 99mTc. The binding and internalization of this compound by B16-F0 melanoma cells has been studied.Results and discussion. The results of labeling SAH with a 99mTc radionuclide under a wide range of conditions were obtained both by the direct method and using the intermediate complex. The target compound rapidly binds to B16-F0 melanoma cells. The degree of internalization is more than 85 %.Conclusion. Based on the results of chemical experiments and data from in vitro experiments, optimal conditions for obtaining a complex compound SAH ∙ 99mTc with a radiochemical yield of more than 90 % were found. The mechanism of binding of this compound to malignant melanoma cells has been established.

Abstract Background Recently, a new family of 99mTc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter (99mTc) and the AO moiety was evaluated for Auger therapy. Among them, 99mTc-C3 places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that 99mTc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the 99mTc-C3 and 99mTc-C5 complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects. Results Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters. Conclusions 99mTc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g., 111In or 161Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer.

Abstract Background For multicenter clinical studies, PET/CT and SPECT/CT scanners need to be validated to ensure comparability between various scanner types and brands. This validation is usually performed using hollow phantoms filled with radioactive liquids. In recent years, 3D printing technology has gained increasing popularity for manufacturing of phantoms, as it is cost-efficient and allows preparation of phantoms of almost any shape. So far, however, direct 3D printing with radioactive building materials has not yet been reported. The aim of this work was to develop a procedure for preparation of 99mTc-containing building materials and demonstrate successful application of this material for 3D printing of several test objects. Method The desired activity of a [99mTc]pertechnetate solution eluted from a 99Mo/99mTc-generator was added to the liquid 3D building material, followed by a minute amount of trioctylphosphine. The resulting two-phase mixture was thoroughly mixed. Following separation of the phases and chemical removal of traces of water, the radioactive building material was diluted with the required volume of non-radioactive building material and directly used for 3D printing. Results Using our optimized extraction protocol with trioctylphosphine as complex-forming phase transfer agent, technetium-99m was efficiently transferred from the aqueous 99Mo/99mTc-generator eluate into the organic liquid resin monomer. The observed radioactivity concentration ratio between the organic phase and the water phase was > 2000:1. The radioactivity was homogeneously distributed in the liquid resin monomer. We did not note differences in the 3D printing behavior of the radiolabeled and the unlabeled organic liquid resin monomers. Radio-TLC and SPECT studies showed homogenous 2D and 3D distribution of radioactivity throughout the printed phantoms. The radioactivity was stably bound in the resin, apart from a small amount of surface-extractable radioactivity under harsh conditions (ethanol at 50 °C). Conclusions 3D printing of radioactive phantoms using 99mTc-containing building materials is feasible. Compared to the classical fillable phantoms, 3D printing with radioactive building materials allows manufacturing of phantoms without cold walls and in almost any shape. Related procedures with longer-lived radionuclides will enable production of phantoms for scanner validation and quality control.

ObjectiveTo prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC).MethodsThe pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7).ResultsThe radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P < 0.01) at pH = 7.4 and the cell-binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The distribution of 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P < 0.01). SPECT/CT imaging was largely consistent with the biodistribution results; the tumor was clearly imaged at each time point after injection of 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7.Conclusion99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.

Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [99mTc]Tc-maSSS-PEG2-RM26 (based on [D-Phe6, Sta13, Leu14-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 °C was monitored for 18 months. The biological properties of [99mTc]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG2-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16–24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [99mTc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without purification, [99mTc]Tc-CNMCHDG had a high radiochemical purity of over 95% and great in vitro stability and hydrophilicity (log P = −3.65 ± 0.10). In vitro cellular uptake studies showed that the uptake of [99mTc]Tc-CNMCHDG was significantly inhibited by pre-treatment with D-glucose and increased by pre-treatment with insulin. Preliminary cellular studies have demonstrated that the mechanism by which the complex enters into cells may be related to GLUTs. The results of biodistribution and SPECT imaging studies displayed high tumor uptake and good retention of [99mTc]Tc-CNMCHDG in A549 tumor-bearing mice (4.42 ± 0.36%ID/g at 120 min post-injection). Moreover, [99mTc]Tc-CNMCHDG exhibited excellent tumor-to-non-target ratios and a clean imaging background and is a potential candidate for clinical transformation.

Broad availability and cost-effectiveness of 99Mo/99mTc generators worldwide support the use, and thus the development, of novel 99mTc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST2) antagonists, mainly due to their superiority in SST2-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a 99mTc-labelled SST2 antagonist, [99mTc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [99mTc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [99mTc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)5 and fac-[NEt4]2[ReBr3(CO)3] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)3] (5a) and fac-[Re(SNO)(CO)3] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[99mTc(CO)3]+ core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[99mTc][Tc(OH2)3(CO)3]+ precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC50 = 8.85 ± 2.62 μM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC50 value of 26.11 nM. Biodistribution studies of the 99mTc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system.

Many radioactive PSMA inhibitory substances have already been developed for PET diagnostics and therapy of prostate cancer. Because PET radionuclides and instrumentation may not be available, technetium-99 m labelled tracers can be considered as a diagnostic alternative. A suitable tracer is [99mTc]Tc-PSMA-I&S, primarily developed for radio-guided surgery, which has been identified for diagnostics of prostate cancer. However, there is no commercial kit approved for the preparation of [99mTc]Tc-PSMA-I&S on the market. This work presents an automated process for the synthesis of [99mTc]Tc-PSMA-I&S concerning good manufacturing practice (GMP). We used a Scintomics GRP 4 V module, with the SCC software package for programming sequences for this development. The optimum reaction conditions were evaluated in preliminary experiments. The pH of the reaction solution was found to be crucial for the radiochemical yield and radiochemical purity. The validation of [99mTc]Tc-PSMA-I&S (n = 3) achieved a stable radiochemical yield of 58.7 ± 1.5% and stable radiochemical purities of 93.0 ± 0.3%. The amount of free [99mTc]TcO4− in the solution and reduced hydrolysed [99mTc]TcO2 was 99mTc]Tc-PSMA-I&S has shown reliability and applicability in the clinical setting.

Albumin nanocolloids have been used as radiopharmaceuticals for more than 40 years. Their main use is in lymphoscintigraphy and the detection of the sentinel lymph node as part of the surgical treatment of a variety of solid tumours. The main licensed products are labelled with the gamma emitter technetium-99m. Recently, two analogues labelled with positron emitters have been reported, using gallium-68 and zirconium-89. For about 10 years, there has been interest in dual-modal agents with both radioactive and fluorescent labels to improve the localisation of the sentinel lymph node. Indocyanine green (ICG) has been the most widely used fluorescent label, largely due to its availability as a licensed agent and its ease of application. The further development of alternative radiolabels or improved fluorescent tags will require investment in the development and licensing. There is also a vast potential for the targeting of albumin nanocolloids using existing strategies, which could be promising for the development of both diagnostic and therapeutic agents.

In chemical processes it is essential that the flow in the process is accurately defined. Fluid velocity measurements are important for fluid flow quality performance in flow systems. This study focuses on determination of the volumetric flow rate and its standard (relative) deviation for calibration of conventional flow meters by using a radiotracer approach. The measurements for flow meter calibration were performed at a pilot-scale flow rig using Technetium-99 m (99mTc) as a radiotracer in the form of pertechnetate ion (99mTcO4-). The measured data were analyzed, and precision of the experimental setup was investigated under two different approaches – IAEA’s RTD software and sum approximation of raw data. For the first time, the variation of standard deviation of calculated flow rate with the injection volume and activity of the radiotracer was determined. Plug flow with axial dispersion was used to simulate the measured RTD curves and investigate the flow dynamics of the flowing water. The results of the study have shown the possibility of in situ calibration of flow meters with a relative error lower than 1 %. They also revealed a slight dependency of the precision of output results on the injection volume as well as similar results for manual and specialized RTD software data processing.

The aim of current study is to develop new nanostructured lipid carrier systems (NLCSs) containing imatinib mesylate (IMT) and evaluate their targeting efficiency on NIH-3T3 as fibroblast cells and CRL-1739 as gastric adenocarcinoma cells with radiolabeled formulations. Three formulations (F1-IMT, F2-IMT and F3-IMT) were prepared and radiolabeled with 1 mCi/0.1 mL of [99mTc]Tc. The effect of reducing and antioxidant agents on radiolabeling process was evaluated and radiochemical purity of formulations was performed by radio thin-layer radiochromatography (RTLC). The results demonstrated that the radiochemical purity was found to be above 90% for [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT, while radiochemical purity of [99mTc]Tc-F3-IMT was found to be 85.61 ± 2.24%. Also, [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT have better stability in cell medium and saline than [99mTc]Tc-F3-IMT. Targeting efficiency of [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT comparatively evaluated by cell binding studies with [99mTc]NaTcO4 on NIH-3T3 and CRL-1739 cells. The cell binding capacity and targeting/non-targeting cell uptake ratio of these two formulations was found to be higher than [99mTc]NaTcO4 in CRL-1739. It is thought that the knowledge achieved in this study would contribute to using [99mTc]Tc-F1-IMT and [99mTc]Tc F2-IMT as an diagnosis and treatment agents.

The aim of this study is to find the optimum conditions of labeling luteolin flavonoid compounds with technetium-99m (99mTc) to meet the purity requirements stated in the United States Pharmacopeia. This compound is expected to be a potential radiotracer compound for diagnosing cancer. The optimization method in labeling luteolin with technetium determines the parameters such as pH, SnCl2.2H2O, genistein concentration, and incubation time. Optimization results of Technetium-99m-luteolin labeling obtained optimum pH conditions 8, the amount of SnCl2.2H2O as a reducing agent 60 μL, the optimum amount of luteolin 6 mg/ml, and the optimum incubation time is 30 min. This optimum condition obtained a99mTc-Luteolin radiochemical purity yield of 94.15%. The radiochemical purity percentage of the99mTc-Luteolin compound has fulfilled the requirements listed at United States Pharmacopeia, which is ≥90%.

As radiation science and technology advances, nuclear medicine applications are increasing worldwide which necessitate the understanding of biological implications of such practices. Ionizing radiation has been shown to cause degraded matrix and reduced proteoglycan synthesis in cartilage, and the late consequences of which may include degenerative arthritis or arthropathy. Although degenerative effects of the ionizing radiation on cartilage tissue have been demonstrated, the effects on the mechanical properties of articular cartilage are largely unknown. The radiopharmaceuticals, technetium-99m and technetium-99m sestamibi, were utilized on bovine articular cartilage to investigate these effects. We used two different mechanical tests to determine the mechanical properties of articular cartilage. Dynamic and static mechanical tests were applied to calculate compressive modulus for articular cartilage. We observed clearly higher control modulus values than that of experimental groups which account for lesser stiffness in the exposed cartilage. In conclusion, compressive moduli of bovine articular cartilage were found to decrease after radiopharmaceutical exposure, after both instantaneous and equilibrium mechanical experiments.

The aim of this study was to synthesis an imaging agent for tumor targeting. New recombinant insulin analogue was successfully produced from E. coli by recombinant DNA technique, and was well labeled with Technetium-99m with a high radiochemical yield of 93.3 ± 2.1 %. Moreover, it showed good in-vitro stability in both saline and human serum. Preclinical evaluation of Technetium-99m [99mTc] Tc-insulin in solid tumor-bearing mice showed high accumulation in tumor tissues. The T/NT (target to non-target ratio) was of 5.4, after 60 min. of post injection (p.i). The direct intra-tumoral (I.T) injection of [99mTc] Tc-insulin showed good retention in tumor tissues with a ratio more than 50 % after 15 min. As a result of the promising bio-distribution studies; the newly recombinant insulin showed good uptake in tumor site, which assured high concentration of insulin receptor on tumor cell surface, accompanied with high cell density of tumor cells as well. This work affords a potential radiocarrier that could be used as a good tumor marker and imaging probe via SPECT (Single Photon Emission Computed Tomography) technique, after further preclinical studies.

Radioembolization (RE) with glass microspheres (MS) loaded with Yttrium-90 (90Y) has been used to treat tumors in the liver with some reported success. However, assessing absorbed doses (AD) in the planning tumor volume (PTV) and normal liver volume (NLV) is a key problem to address in RE. In clinical practice, the computation of 90Y activity to be administered follows the manufacturer’s recommendations, which do not consider the specific characteristics of MS deposition in each patient’s liver. Our main aim is to develop a methodology to estimate the optimal activity for each patient treatment. It uses the absorbed dose distribution (ADD) derived from the Technetium-99m (99mTc)-labeled macroaggregated albumin (MAA) obtained from pre-treatment planning single-photon emission computed tomography (SPECT) images. Post-treatment positron emission tomography (PET) images of the 90Y-MS distribution were used to estimate the ADD for treatment verification. Sixteen RE treatments were retrospectively selected. The agreement between the estimated mean AD based on the planning imaging and real post-treatment mean AD was good in PTV with an intraclass correlation coefficient (ICC) of 0.79 and excellent in NLV (ICC = 0.97). The optimization of 90Y activity using pre-defined clinical AD thresholds (80 Gy in PTV) imposed on the PTV and NLV voxels showed remarkably high agreement (ICC = 0.96, p < 0.001) in eleven out of the sixteen RE treatments between SPECT-MAA-based and PET-MS-based optimal activity estimates. In conclusion, under well-controlled conditions, pre-treatment SPECT-MAA imaging predicts well the treatment of ADD. In addition, SPECT-MAA imaging can be used to optimize the 90Y-MS activity to be administered to the liver.

Current radiolabeled gastrin-releasing peptide receptor (GRPR) ligands usually suffer from high accumulation in GRPR-positive organs (pancreas, stomach), limiting tumor-to-background contrast in the abdomen. In novel N4-bombesin derivatives this was addressed by substitutions at the Gln7-Trp8 site within the MJ9 peptide (H-Pip5-phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) either by homoserine (Hse7), β-(3-benzothienyl) alanine (Bta8) or α-methyl tryptophan (α-Me-Trp8), with the aim of optimizing pharmacokinetics. We prepared and characterized the peptide conjugates 6-carboxy-1,4,8,11-tetraazaundecane (N4)-asp-MJ9, N4-asp-[Bta8]MJ9, N4-[Hse7]MJ9 and N4-[α-Me-Trp8]MJ9, and evaluated these compounds in vitro (GRPR affinity via IC50,inverse; internalization; lipophilicity via logD7.4) and in vivo (biodistribution and μSPECT/CT studies at 1 h post injection (p.i.) in PC-3 tumor-bearing CB17-SCID mice). 99mTc-labeling resulted in radiochemical yields (RCYs) > 95%. All 99mTc-labeled MJ9 analogues showed comparable or higher GRPR affinity than the external reference [99mTc]Tc-Demobesin 4. Receptor-bound fractions were noticeably higher than that of the reference. Despite a slightly enhanced lipophilicity, all novel MJ9 derivatives revealed improved in vivo pharmacokinetics compared to the reference. The Bta8-modified ligand revealed the most favorable tumor-to-abdomen contrast at 1 h p.i. Substitutions at the Gln7-Trp8 site within GRPR ligands hold great potential to modify pharmacokinetics for improved imaging.