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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.

Specific and accurate diagnostic tools are important to determine diagnosis for various lung diseases with complex characteristics. In this study, high-energy milling (HEM) was utilized to prepare micro-sized carbon from palm kernel shell charcoal as a potential aerosol agent for lung ventilation scintigraphy. The HEM parameters investigated in this experiment were milling time and ball-to-powder ratio (BPR), while the characterization of the obtained powder involves particle size distribution, porosity, specific surface area, and XRD pattern. The optimization of technetium-99m (99mTc) labeling of the obtained carbon powder was carried out concerning SnCl2 amount, carbon dosage, incubation time, and pH. The optimal milling time and BPR were 180 min and 5:1, respectively, resulting in Dx(50) of 1.71 µm. Generally, the 99mTc labeling yield increased with the increase of SnCl2 amount, carbon dosage, and incubation time, while it decreased as the pH increased. The optimal 99mTc labeling condition, SnCl2 amount of 300 µg, carbon dosage of 50 mg, incubation time of 30 min, and pH 5, resulted in an adsorption capacity of 178.89 TBq of 99mTc/g carbon. These results demonstrate that aerosol scintigraphy agents can potentially be prepared from palm kernel shell charcoal with optimization of radiolabeling method, milling process, and further in vitro aerosol performance prior to pre-clinical and clinical stages. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Cancer diagnosis involves a multi-step process. Accurate identification of the tumor, staging and development of cancer cells is crucial for selecting optimal treatments to minimize disease recurrence. Quantum dots (QDs) represent an exciting class of fluorescent nanoprobes in molecular detection and targeted tumor imaging. Materials and methods: In this study, graphene quantum dots (GQDs) were synthesized by pyrolysis of citric acid (CA) as a carbon precursor under high temperatures. The morphology of the obtained GQDs was first characterized using physical (TEM and DLS) and spectroscopic (fluorescence, FTIR and UV–Vis) methods. In the following,99mTc-labeled GQDs were prepared in the presence of SnCl2.2H2O as a reducing agent between 95 and 100 °C. The biodistribution and tumor targeting efficiency of radiolabeled GQDs as a novel agent for C6 glioma tumor scintigraphy in an animal model were evaluated. Furthermore, organ uptake, human serum albumin binding and tumor accumulation were measured. Results: The TEM image of the prepared GQDs showed a relatively uniform size distribution in the range of diameter 6-9 nm and spherical shape. Radiolabeled GQDs showed a radiochemical yield of >97% (n = 3). Through incubation in human serum, almost 15% of 99mTc-labeled GQDs degraded after 6 h. The amount of uptake in xenograft models of glioma C6 rats was 1.10 ± 0.36% of injection dose per gram after 1 h. The kidneys, intestinal and glioma tumor sites were observed via scintigraphy imaging. Conclusion: Our data suggest that 99mTc-labeled GQDs, as a new radiotracer, efficiently accumulate in the tumor site and could be included as a radiotracer for detecting glioma tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Carum carvi-derived quantum dots (CcQDs) were prepared using thermal pyrolyzing. The surface functionalization of CcQDs were achieved via L-cysteine ligand. Labeled CcQDs with technetium-99m were prepared using a simple direct radiolabeling method. Radio chromatographic techniques were used to analyze radiochemical yield. Quality control results indicated that QDs could be efficiently labeled with 99mTc-radionuclide (> 98% radiochemical yield). The in vivo biodistribution parameters were studied in tumorized BALB/c mouse. The amount of uptake in xenograft models of mice colon carcinoma was 1.27 ± 0.15% ID/g after 1 h. 99mTc-labeled T-Cysteine-CcQDs, could be included as a radiotracer for imaging colon carcinoma tumors. [ABSTRACT FROM AUTHOR]

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.

Background/Objectives: Heterodimer peptides targeting more than one receptor can be advantageous, as tumors can simultaneously express more than one receptor type. For human breast cancer, a promising biological target is tumor angiogenesis through αvβ3 integrin expression. Another promising target is Neuropeptide Y receptors, considering Y1R is overexpressed in 90% of human breast tumors. This article details the development and preclinical evaluation, both in vitro and in vivo, of a novel heterodimer peptide dual-receptor-targeting probe, [99mTc]HYNIC-cRGDfk-NPY, designed for imaging breast tumors. Methods: Female BALB/c healthy mice were used to perform biodistrubution studies and female SCID mice were subcutaneously injected with MCF-7 and MDA-MB-231 tumor cells. [99mTc]HYNIC-cRGDfk-NPY was intravenously administered to the mice, followed by ex vivo biodistribution studies and small-animal SPECT/CT imaging. Nonspecific tracer uptake in both models was determined by coinjecting an excess of unlabeled HYNIC-cRGDfk-NPY (100 µg) along with the radiolabeled tracer. Results: Imaging and biodistribution data demonstrate good uptake to estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) tumor models. The in vivo tumor uptakes of radiolabeled conjugate were 9.30 ± 3.25% and 4.93 ± 1.01% for MCF-7 and MDA-MB231, respectively. The tumor/muscle ratios were 5.65 ± 0.94 for the MCF-7 model and 7.78 ± 3.20 for MDA-MB231. Conclusions: [99mTc]HYNIC-cRGDfk-NPY demonstrated rapid blood clearance, renal excretion, and in vivo tumor uptake, highlighting its potential as a tumor imaging agent. [ABSTRACT FROM AUTHOR]

Objective: Prostate-specific membrane antigen (PSMA) is a well-known biomarker of prostate cancer. Previously, our group reported that the succinimidyl–cystatin–urea–glutamate (SCUE) moiety has a high affinity for PSMA. In this study, we developed the novel technetium-99m-labeled PSMA-targeting probe "[99mTc]Tc-(Ham-SCUE)2" based on a hydroxamamide chelate with a bivalent SCUE and evaluated its potential as a SPECT imaging probe for the diagnosis of PSMA-expressing prostate cancer. Methods: Ham-SCUE was synthesized by a one-step reaction with Ham-Mal and cysteine-urea-glutamine. Then, Ham-SCUE was reacted with [99mTc]NaTcO4 for 10 min at room temperature to obtain [99mTc]Tc-(Ham-SCUE)2. [99mTc]Tc-(Ham-SCUE)2 was added to LNCaP (high PSMA expression) cells or PC3 (low PSMA expression) cells, and their radioactivity was measured 60 min after administration. The blocking study was performed by co-incubation of LNCaP cells with various concentrations of 2-PMPA (a PSMA inhibitor) for 15 min before adding [99mTc]Tc-(Ham-SCUE)2. The biodistribution of [99mTc]Tc-(Ham-SCUE)2 in LNCaP/PC3 dual xenografted C.B.-17/Icr scid/scid Jcl mice was evaluated for 120 min after intravenous injection. The blocking study was performed by pretreatment of mice with 2-PMPA (10 mg/kg weight). Results: [99mTc]Tc-(Ham-SCUE)2 was acquired at radiochemical yields of 56% with a radiochemical purity of over 95%. The cellular uptake level of [99mTc]Tc-(Ham-SCUE)2 by LNCaP cells was significantly higher than that by PC3 cells (LNCaP: 11.12 ± 0.71 vs. PC3: 1.40 ± 0.13%uptake/mg protein, p < 0.01), and the uptake was significantly suppressed by pretreatment with 2-PMPA (2.56 ± 0.37%uptake/mg protein, p < 0.05). IC50 of 2-PMPA was 245 ± 47 nM. In the in vivo study, the radioactivity of LNCaP tumor tissue was significantly higher than that of PC3 tumor tissue at 120 min after the administration of [99mTc]Tc-(Ham-SCUE)2 (LNCaP: 9.97 ± 2.79, PC3: 1.16 ± 0.23%ID/g, p < 0.01), and was suppressed by pretreatment with 2-PMPA (2.50 ± 0.45%ID/g, p < 0.01). Conclusion: [99mTc]Tc-(Ham-SCUE)2 has the potential to be a SPECT imaging agent for diagnosing high PSMA-expressing prostate cancer. [ABSTRACT FROM AUTHOR]

The 2‐nitroimidazole based 99mTc‐radiopharmaceuticals are widely explored for imaging tumor hypoxia. Radiopharmaceuticals for targeting hypoxia are often lipophilic and therefore, show significant uptake in liver and other vital organs. In this context, lipophilic radiopharmaceuticals with design features enabling faster clearance from liver may be more desirable. A dipicolylamine‐NCS bifunctional chelator that could generate a thiourea‐bridge up on conjugation to primary amine bearing molecule was used to synthesize a 2‐nitroimidazole‐dipicolyl amine ligand for radiolabeling with 99mTc(CO)3 core. Corresponding Re(CO)3‐analogue was prepared to establish the structure of 2‐nitroimidazole‐99mTc(CO)3 complex prepared in trace level. The 2‐nitroimidazole‐99mTc(CO)3 complex showed a hypoxic to normoxic ratio of ~2.5 in CHO cells at 3 h. In vivo, the complex showed accumulation and retention in tumor with high tumor to blood and tumor to muscle ratio. The study demonstrated the utility of metabolizable thiourea‐bridge in 2‐nitroimidazole‐99mTc(CO)3 complex in inducing faster clearance of the radiotracer from liver. The dipicolylamine‐NCS bifunctional chelator reported herein can also be used for radiolabeling other class of target specific molecules with 99mTc(CO)3 core. [ABSTRACT FROM AUTHOR]

Organometallic complexes of fac-tricarbonylrhenium have been shown to exhibit anticancer properties. Anthrapyrazole anticancer agents act as DNA intercalators and topoisomerase IIα inhibitors, leading to double-strand breaks (DBS) and cell cycle arrest. This work involves the synthesis and biological evaluation of novel fac-tricarbonyl-rhenium complexes with anthrapyrazole derivatives. The anthrapyrazole moiety was synthesized from 1,8-dihydroxyanthraquinone, and three ligands L1, L2 and L3 were prepared. Ligand L1 coordinates via the phenolic O and pyrazole N as bidentate chelator forming the fac-[Re(CO)3(κ2-N,O)(MeOH)]-type complex, ReL1. Ligand L2 contains a pendant picolylamine N,N′-chelating system, forming the bidentate fac-[Re(CO)3(κ2-N,N′)Br]-type complex, ReL2. Ligand L3 contains a pendant picolylaminomonoacetic acid chelating system, forming a tridentate fac-[Re(CO)3(κ3-N,N′,O)]-type complex, ReL3. Complex ReL4 contains a picolylamine chelator, forming a complex with structure fac-[Re(CO)3(κ2-N,N′)Br], which was synthesized as a model for ReL2, and its coordination mode was resolved by X-ray crystallography. The complexes were characterized spectroscopically, and their biological properties were evaluated in vitro, in terms of DNA binding as well as for the cytotoxicity against CT-26 tumor cell line. Tumor cell cytotoxicity was high for ligand L2 and complex ReL2, exhibiting IC50 values of 0.36 and 0.64 μΜ, respectively. The most promising complex ReL2 was evaluated further by the preparation of its congener γ-emitting technetium-99m radio-complex, 99mTcL2. The in vitro uptake in CT26 tumor cells and the in vivo uptake in CT26 tumor-bearing mice of 99mTcL2 was determined, and its pharmacokinetic profile was established. These data indicate that the 99mTc complex has suitable properties to enter tumor cells in vitro and in vivo, and therefore ReL2 is promising for further evaluation. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

In this study, a new nano-structure, N,P-doped graphene quantum dots (N,P-GQDs), were synthesized as multipurpose imaging agent for performing scintigraphy and magnetic resonance imaging (MRI). Some standard characterization methods were used to identify the nano-structure. In vitro cytotoxicity evaluation using MTT assay revealed that N,P-GQDs nanoparticles had no significant cytotoxicity after 24 and 48 h against normal (MCF-10A) and cancerous (MCF 7) human breast cell line in concentration up to 200 μg/mL. The N,P-GQDs were radiolabeled with Technetium-99m as 99mTc-(N,P-GQDs) and the radiochemical purity was assayed by ITLC concluding RCP ≥ 95 %. The passing of 99mTc-(N,P-GQDs) through 0.1 µm filter demonstrated that 70.8 % of particles were <0.1 µm. In order to perform scintigraphy, the 99mTc-(N,P-GQDs) were injected to female healthy Wistar rats. The results showed that the radio-complex was captured and eliminated just by kidneys. Moreover, in vitro T1-weighted phantom MRI imaging showed that the N,P-GQDs have proper relaxivity in comparison to Dotarem® as a clinically available contrast agent. The results showed that the N,P-GQDs have potential to be considered as a novel and encouraging agent for both molecular MRI and nuclear medicine imagings. [ABSTRACT FROM AUTHOR]

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.

Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc‐radiolabeled and tofacitinib citrate‐encapsulated microsphere loaded poloxamer in situ gel formulations for the intra‐articular treatment. Among nine different microsphere formulations, MS/TOFA‐9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra‐articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA‐9 and PLX‐MS/TOFA‐9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti‐inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc‐MS/TOFA‐9 and 99mTc‐PLX‐MS/TOFA‐9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX‐MS/TOFA‐9 was found to be a promising agent for intra‐articular injection in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

In this study, we compared in vitro and in vivo results of the 99mTc-labeled HYNIC-KRWrNM in the presence of Tricine/EDDA and Tricine/Nicotinic acid (NA) as two co-ligand systems ([99mTc]Tc-M-7 and [99mTc]Tc-M-6, respectively). The dissociation constant (Kd) value of [99mTc]Tc-M-6 was 7.1 ± 2.3 nM for U87-MG cell line (glioblastoma). Based on biodistribution studies, the tumor-to-muscle ratio of [99mTc]Tc-M-6 was 8.77 and 11.33 at 1.5 and 4 h after injection, respectively. Finally, target-to-background ratio in the planar gamma image was 12.03 at 4 h after injection. By comparison, our experimental results showed that substitution of EDDA by Nicotinic acid in the 99mTc-labeling of HYNIC-KRWrNM led to the formation of an improved tumor-targeting peptide. This improved radio-peptide can be a potential agent for the diagnosis of integrin αvβ3-positive tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of Prostate cancer (PCa). In this study, we introduce the freeze-dried kit formulation of [99mTc]Tc-HYNICALUG for easy clinical evaluation of prostate cancer. Methods: In this work, an in silico modeling of the urea-based PSMA small molecule (HYNIC-ALUG) was performed to check its interaction with human glutamate carboxypeptidase II and compared it with experimental results. The HYNIC-PSMA kit was formulated for easy preparation of [99mTc]Tc-HYNIC-ALUG. The kit contained a freeze-dried mixture of HYNIC-ALUG, coligands SnCl2.2H2O, and antioxidant D-mannitol. Results: The calculated Ki value (inhibition/dissociation constant) was 4.55 which showed excellent binding affinity of HYNIC-ALUG with PSMA. miLogP and cLogS values are -4.04 and -3.07 respectively showing its hydrophilic character and predicting its excellent distribution in biological fluids. Subsequently, the radiochemical purity of the HYNIC-PSMA kit was 99.1 ± 1.32% (n = 6) determined by radio-ITLC and by HPLC as well. In vitro stability in saline and serum was studied up to 4 h and showed high stability (≥ 96%). The distribution of [99mTc]Tc-HYNIC-ALUG was carried out in two patients and SPECT/CT planar images were acquired at 2h and 4h respectively. Bio-physiological distribution of [99mTc]Tc- HYNIC-ALUG was observed normally in lacrimal, salivary glands, liver, spleen, gut, kidneys, and urinary bladder. Conclusion: The HYNIC-ALUG freeze-dried kit could be used for easy preparation of [99mTc]Tc-HYNIC-ALUG and can be considered as a potential agent for the diagnosis, staging, and restaging of advanced prostate cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Xanthomicrol (4′,5-dihydroxy-6,7,8-trimethoxyflavone) is the main active component of Dracocephalum kotschyi Boiss leaf extract. It has showed selective cytotoxic activity against some cancer cell lines and little effect on human fetal foreskin fibroblast cells used as nonmalignant control. This study aimed to develop 99mTc-labeled xanthomicrol and to evaluate its efficiency as a new tumor imaging agent. l,l-Ethylene dicysteine (EC) chelator was conjugated to xanthomicrol. EC-Xanthomicrol was labeled with technetium-99m by using tin chloride as a reducing agent and incubating at room temperature. Radiochemical purity and in vitro stability were analyzed by thin layer chromatography and high-performance liquid chromatography. In vitro cellular uptake and binding profile of radio-conjugate was determined on C6 glioma cells. In vivo bioevaluation and imaging studies of [99mTc]Tc-EC-Xanthomicrol were performed in C6 glioma tumor induced rat at different time points after injection of radio-conjugate. The high radiochemical yield (>95 %) was achieved for [99mTc]Tc-EC-Xanthomicrol which was stable up to 6 h. The radio-conjugate indicated high cell uptake (35.12 % at 2 h) which demonstrated to be specific. Tumor uptake was seen for [99mTc]Tc-EC-Xanthomicrol (1.23 ± 0.14 %ID/g) at 1 h post injection. Scintigraphy confirmed that tumors could be visualized clearly with [99mTc]Tc-EC-Xanthomicrol. The results indicated that [99mTc]Tc-EC-Xanthomicrol has potential to be considered as a new radiotracer in glioma tumor imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Previously, we designed the EuK-based PSMA ligand BQ0413 with an maE3 chelator for labeling with technetium-99m. It showed efficient tumor targeting, but our preclinical data and preliminary clinical results indicated that the renal excretion levels need to be decreased. We hypothesized that this could be achieved by a decrease in the ligand's total negative charge, achieved by substituting negatively charged glutamate residues in the chelator with glycine. The purpose of this study was to evaluate the tumor targeting and biodistribution of two new PSMA inhibitors, BQ0411 and BQ0412, compared to BQ0413. Conjugates were radiolabeled with Tc-99m and characterized in vitro, using PC3-pip cells, and in vivo, using NMRI and PC3-pip tumor-bearing mice. [99mTc]Tc-BQ0411 and [99mTc]Tc-BQ0412 demonstrated PSMA-specific binding to PC3-pip cells with picomolar affinity. The biodistribution pattern for the new conjugates was characterized by rapid excretion. The tumor uptake for [99mTc]Tc-BQ0411 was 1.6-fold higher compared to [99mTc]Tc-BQ0412 and [99mTc]Tc-BQ0413. [99mTc]Tc-BQ0413 has demonstrated predominantly renal excretion, while the new conjugates underwent both renal and hepatobiliary excretion. In this study, we have demonstrated that in such small targeting ligands as PSMA-binding EuK-based pseudopeptides, the structural blocks that do not participate in binding could have a crucial role in tumor targeting and biodistribution. The presence of a glycine-based coupling linker in BQ0411 and BQ0413 seems to optimize biodistribution. In conclusion, the substitution of amino acids in the chelating sequence is a promising method to alter the biodistribution of [99mTc]Tc-labeled small-molecule PSMA inhibitors. Further improvement of the biodistribution properties of BQ0413 is needed. [ABSTRACT FROM AUTHOR]

Using a one-pot cyclo-condensation process under microwave irradiation, derivatives of curcumin have been created. Evaluation their anti-inflammatory efficacy showed that they had stronger properties than curcumin. Additionally, the most active derivative was radiolabeled with the diagnostic radioisotope technetium-99m and prepared with a high radiochemical yield (96.5 ± 0.09%) and in vitro stability of up to 6 h. The in-vivo study in inflamed mice showed that [99mTc]Tc-curcumin derivative accumulated with a high target to non-target ratio. The gathered information confirmed the efficacy of the [99mTc]Tc-curcumin derivative as a novel possible tracer for the identification and localization of inflammation. [ABSTRACT FROM AUTHOR]

Synaptic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is thought to cause excitotoxicity brain ischemia. However, given the current inability to quantify AMPARs density in live human brains, clinical translation has been limited. In this study, in vivo and in vitro experiments were conducted to evaluate the factors affecting omberacetam drug labeling with technetium-99m as a potential radiotracer of AMPARs in brain imaging. Healthy Swiss albino mice (adult male; n = 25; weight 25–30 g; age 10–14 weeks) underwent Shimadzu modeling, followed by a random intravenous injection of 99mTc-omberacetam (0.2 mL, 3.7 MBq), which was subsequently radiosynthesized in the brain-targeting AMPARs utilizing a single-photon emission computed tomography nuclear neuroimaging. Under optimal conditions, 99mTc-omberacetam with a highest radiochemical purity of 98.9% was obtained with an optimum binding (energy = − 82.3 kcal/mol) to brain AMPARs and was stable in human serum for > 24 h. A high brain uptake was noted within a time window of 15–60 min. At 5 min, this signal uptake was 8.9 ± 0.1% of the injected dose per gram (ID/g), crossing the blood–brain barrier and surpassing the uptake of commercially available brain perfusion imaging agents such as 125I-iododomperidone (5.6% ID/g at 5 min) in mice, 99mTc-HMPAO (2.25% ID/g at 2 min) in rats, and 99mTc-ECD (4.7% ID/g at 6 h) in humans. This study is the first to show the feasibility of 99mTc-omberacetam radiotracing for human brain imaging. This could be a novel diagnostic and therapeutic neuroprotective target for the hyperacute stage of ischemic stroke. [ABSTRACT FROM AUTHOR]

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.

The radiolabeled iron oxide nanoparticles constitute an attractive choice to be used as dual-modality contrast agents (DMCAs) in nuclear medical diagnosis, due to their ability to combine the benefits of two imaging modalities, for instance single photon emission computed tomography (SPECT) with magnetic resonance imaging (MRI). Before the use of any DMCA, the investigation of its plasma extra- and on/intra cellular distribution in peripheral human blood is of paramount importance. Here, we focus on the in vitro investigation of the distribution of 99mTc-DPD-Fe3O4 DMCA in donated peripheral human blood (the ligand 2-3-dicarboxypropane-1-1-diphosphonic-acid is denoted as DPD). Initially, we described the experimental methods we performed for the radiosynthesis of the 99mTc-DPD-Fe3O4, the preparation of whole blood and blood plasma samples, and their incubation conditions with 99mTc-DPD-Fe3O4. More importantly, we employed a gamma-camera apparatus for the direct imaging of the 99mTc-DPD-Fe3O4-loaded whole blood and blood plasma samples when subjected to specialized centrifugation protocols. The direct comparison of the gamma-camera data obtained at the exact same samples before and after their centrifugation enabled us to clearly identify the distribution of the 99mTc-DPD-Fe3O4 in the two components, plasma and cells, of peripheral human blood. [ABSTRACT FROM AUTHOR]

Background: Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra. SPECT imaging using technetium-99m [99mTc] labeled trodat is the choice of imaging to differentiate PD from its other forms like drug-induced PD. Aims and Objectives: The main objective of our study was to prepare in-house sterile formulation of [99mTc]Tc-trodat and use in clinics. Materials and Methods: The labeling of trodat was standardized using glucoheptonate sodium salt (GHA), stannous chloride dihydrate (in 0.05 N HCl), and ethylenediaminetetraacetic acid (Na-EDTA). The preparation was mixed and autoclaved at 15 psi for 15 min. The standardised formulation was stored at 4°C, -20°C and -80°C and labeling with 99mTc was tested for up to 6 days. The radiochemical purity, chemical impurities, and endotoxin levels were tested. The frozen formulation was tested in swiss mice (n = 3) for biodistribution studies at 4 h. Around 18 ± 2 mCi was injected intravenously in each patient (n = 5) and the image was acquired at 4 h post-injection. Results: The radiochemical purity of the preparation was 98.3 ± 1.4% with a retention time of 16.8 ± 1.5 min as compared to 4.0 ± 0.5 min for free 99mTc. Animal distribution showed highest uptake in liver and dual excretion via hepatobiliary and renal system. [99mTc]Tc-trodat imaging was able to differentiate both caudate and putamen. Conclusions: In-house frozen preparation was advantageous, as it has decreased the chance of manual error as compared to daily make up formulations and economical as compared to commercially available kits. [ABSTRACT FROM AUTHOR]

Acetaminosalol labeling reaction with technetium‐99m was optimized, and the radiocomplex was obtained in a high radiochemical yield of 98.9 ± 0.6% and high stability (>30 h). The tracer was characterized, and its binding to the PPARγ receptor was assessed in silico. To reduce radiation exposure to non‐target organs and increase accumulation in the colon, the tracer was formulated as pH‐sensitive microspheres with a mean particle size of 201 ± 2.1 μm, a polydispersity index of 0.18, a 25.3 ± 3.6 zeta potential, and 98.6 ± 0.33% entrapment efficiency. The system suitability was assessed in vivo in normal and ulcerative rats, and the biodistribution profile in the colon showed 56.5 ± 1.4% localization within 4 h. Blocking study suggested the selectivity of the tracer to the target receptor. Overall, the reported data encouraged the potential use of the labeled microspheres to target ulcerative colitis. [ABSTRACT FROM AUTHOR]

Metallothioneins are a special group of low-molecular-weight proteins with metal-binding properties, which make them promising chelators for the development of targeted radiopharmaceuticals, as well as with technetium-99m. The aim of this work is to study the biodistribution of 99mTc-metallothionein conjugate (99mTc-MT) in intact mice in comparison with unbound technetium-99m (Na99mTcO4). Low uptake of 99mTc-MT in the thyroid gland (1.20 ± 0.30%/g versus 267.2 ± 59.0%/g for Na99mTcO4) demonstrates the high stability of 99mTc-MT in vivo. The 99mTc-MT complex is rapidly eliminated from the bloodstream through the kidneys and is characterized by a reduced uptake in most organs and tissues compared to Na99mTcO4. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA), which is overexpressed in advanced prostate cancer, is a well-established target for the development of antitumor diagnostic and therapeutic radiopharmaceuticals. The aim of this work is the preclinical study of the pharmacokinetics of a new radiopharmaceutical 99mTc-PSMA. Tumor uptake of 99mTc-PSMA is 1.81–3.91%/g with a maximum uptake of 3.91 ± 0.35%/g at 3 h of post-injection. The highest uptake (up to 140.11%/g) of 99mTc-PSMA throughout the study was observed in the kidneys. Tumor uptake of 99mTc-PSMA was higher than in other organs and tissues, except the kidneys [ABSTRACT FROM AUTHOR]

Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [99mTc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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.

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. [ABSTRACT FROM AUTHOR]

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.