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 logD_7.4 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.

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its ^99mTc analog (Complex 2’) by incorporating triphenylphosphine instead of bromine as the monodentate ligand and ${\mathrm{P}\mathrm{F}}_6^{-}$ as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The ^99mTc complex’s radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC₅₀ of 2.6 μM and EGFR phosphorylation inhibition with an IC₅₀ of 130.6 nM. Both complex 1 and 2 induced G₀/G₁ cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2’ demonstrated high stability and favorable lipophilicity (LogD_7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2’ show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.

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.

Background: Gastrin-releasing peptide receptor (GRPR)-targeted radioligands are promising tools for imaging and treatment of GRPR-expressing malignancies. This study aimed to develop a NOTA-P2-RM26-based ^99mTc/¹⁸⁸Re theranostic pair using the fac-[M(CO)₃]⁺ core, with fac-[^99mTc][Tc(CO)₃(NOTA-P2-RM26)], ^99mTc2, as the diagnostic SPECT analogue and fac-[¹⁸⁸Re][Re(CO)₃(NOTA-P2-RM26)], ¹⁸⁸Re2, as the potential therapeutic counterpart. Methods: NOTA-P2-RM26 was radiolabeled with the fac-[^99mTc(CO)₃(H₂O)₃]⁺, ^99mTc1, precursor after systematic optimization of peptide amount, pH, buffer, temperature, and reaction time. The radioconjugate was purified by HPLC, reformulated by solid-phase extraction, and evaluated by radio-HPLC and radio-TLC. We assessed stability in the formulation, human serum, cysteine and histidine over 6 h. Lipophilicity was determined as logD_7.4. We evaluated in vitro specificity, cell association, and internalization in PC-3 cells. We performed biodistribution, blocking, dynamic imaging, and SPECT/CT imaging in PC-3 xenograft-bearing mice. The corresponding ¹⁸⁸Re analog was prepared under analogous conditions and evaluated for physicochemical matching. Results: Optimized labeling afforded ^99mTc2 with approximately 85% radiochemical conversion and >97% radiochemical purity after purification. The compound remained stable in formulation, with 93% of the tracer intact after 6 h, and exhibited a hydrophilic profile (logD_7.4 = −1.5 ± 0.2). In PC-3 cells, uptake reached 20.0 ± 1.0% of added activity and was reduced to 1.4 ± 0.3% under blocking conditions. In vivo, tumor uptake was 15.0 ± 1.0 %IA/g at 30 min and 17.0 ± 2.2 %IA/g at 1 h p.i. Blocking reduced tumor uptake to 0.84 ± 0.12 %IA/g, corresponding to approximately 95% inhibition. Pancreatic uptake decreased from 8.0 ± 0.4 %IA/g at 30 min to 3.0 ± 0.35 %IA/g at 1 h and was reduced to 0.20 ± 0.08 %IA/g after blocking. At 1 h p.i., tumor-to-blood, tumor-to-muscle, tumor-to-pancreas, and tumor-to-kidney ratios were approximately 21.3, 130.8, 5.7, and 3.6, respectively. SPECT/CT imaging confirmed clear, blockable visualization of the PC-3 tumor. The ¹⁸⁸Re analog was obtained with approximately 80% radiochemical conversion and >95% radiochemical purity post purification. It showed similar stability values to ^99mTc2 under the tested conditions and a logD_7.4 of −1.6 ± 0.2. Conclusions: Complex ^99mTc2 demonstrated efficient preparation, high stability, GRPR-mediated tumor uptake, favorable tumor-to-background ratios, and clear SPECT/CT visualization of PC-3 xenografts. The corresponding ¹⁸⁸Re analog supports the feasibility of a chemically matched ^99mTc/¹⁸⁸Re NOTA-P2-RM26 theranostic platform and warrants further evaluation of ¹⁸⁸Re biodistribution, dosimetry, and therapeutic efficacy.