Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson's Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods.

Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99 m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography-mass spectrometry (LC-MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [99mTc]Tc radiolabeled compounds ([99mTc]Tc-MA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague-Dawley rats and a Parkinson's disease experimental model to evaluate the compounds' bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6 h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.

The Radiolabeling of [161Tb]-PSMA-617 by a Novel Radiolabeling Method and Preclinical Evaluation by In Vitro/In Vivo Methods.

Background: Prostate cancer (PC) is the most common type of cancer in elderly men, with a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently, [161Tb], a radiolanthanide introduced for treating micrometastatic foci, has shown great promise for treating prostate cancer. Results: In this study, Terbium-161 [161Tb]Tb was radiolabeled with prostate-specific membrane antigen (PSMA)-617 ([161Tb]-PSMA-617) and the therapeutic efficacy of the radiolabeled compound investigated in vitro and in vivo. [161Tb]-PSMA-617 was found to have a radiochemical yield of 97.99 ± 2.01% and was hydrophilic. [161Tb]-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 hours. In vitro, [161Tb]-PSMA-617 showed a cytotoxic effect on LNCaP cells but not on PC-3 cells. In vivo, scintigraphy imaging visualized the accumulation of [161Tb]-PSMA-617 in the prostate, kidneys, and bladder. Conclusions: The results suggest that [161Tb]-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer.

EFFECTIVE HALF-LIFE, EXCRETION AND RADIATION EXPOSURE OF 177LU-PSMA.

The study aims to evaluate the radiation safety conditions by detecting the patient's urine excretion rate, calculating the effective half-life, and determining the retention of 177Lu-PSMA in the body. Urine samples of patients were collected for 24 hours (6, 12, 18, and 24 hours) following the infusion, excretion rate and retention of 177Lu-PSMA in the body of patients were calculated. The measurements of dose rate were performed. Effective half-life calculated from dose rate measurements was found as 18.5 ± 11 h within the first 24 h and 48.1 ± 22.8 h between 24 and 72 h. Excreted activity in urine was found as 33.8 ± 20.7, 40.4 ± 20.3, 46.1 ± 22.4, and 53.3 ± 21.5% of total doses at 6, 12, 18, and 24 h after administration, respectively. External dose rates for 4 h and 24 h were 24.51 µSv/h, 16.14 µSv/h, respectively. Our results showed that 177Lu-PSMA treatment was suitable for outpatient treatment in terms of radiation safety.

Inguinoscrotal Bladder Hernia Mimicking Testicle Tumor.

Bladder hernias usually begin asymptomatically and are discovered incidentally at the time of discovery. Preoperative diagnosis of bladder hernias is important to reduce the risk of bladder injury during surgery. Although F-18 FDG PET/CT is applied for oncological purposes, benign conditions should also be taken into account when evaluating the implants. In this article, a case of bladder hernia, which can be confused with pathological cancer involvement, with the diagnosis of F-18 FDG PET/CT performed in a 73-year-old male patient with renal cell carcinoma is presented.

Contribution of Open Mouth Technique in 18F-FDG PET/CT Imaging in Patients with Malignant Lip Neoplasm.

Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating head and neck cancers. However, localization and size evaluation in this region can be rough due to the multitude of the anatomic structures and physiologic uptakes. The aim of this study was to evaluate malignant lip lesions with the contribution of open mouth (OM) imaging technique at PET/CT. Methods: Fifty-six patients with malignant lip neoplasm underwent 18F-FDG PET/CT imaging. Each patient was imaged twice as whole-body PET/CT with routine closed mouth (CM) position; and OM head and neck image, standardized with a special device. Lesion maximum standard uptake value (SUVmax), localization, size, and involvement of lymph nodes were evaluated. Results: Lesion localization was correctly detected in 100% of the OM images. Lesion size in PET/CT was compared with clinical, radiological (magnetic resonance imaging and CT) and/or histopathological results and the size measurement was coherent at 47.1% and 95.6% for CM and OM images, respectively. It was observed that OM acquisition did not contribute additionally in detecting regional lymph node metastasis. Forty-one PET/CT scans with CT artifacts due to dental amalgams were evaluated and 46.3% dimensional and 53.7% localization errors were detected in the CM position. There was no statistically significant difference between OM and CM SUVmax (p>0.05). Conclusion: We concluded that additional OM head and neck imaging is useful and necessary to accurately determine the localization and size of the tumor, thus enhancing the value of PET/CT in staging, treatment response assessment, and restaging of patients with malignant lip cancer with or without dental amalgam.

Unexpected Metastatic Localizations of Prostate Cancer Determined by 68Ga PSMA PET/CT: Series of Four Cases.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein with overexpression in most prostate cancer cells. Gallium-68-(68Ga) PSMA positron emission tomography/computed tomography (PET/CT) imaging is a game-changer in the management of prostate cancer. 68Ga PSMA PET/CT scan is advanced and a promising radioligand has high sensitivity in determining lesions of prostate cancer with a high tumor to background ratio. The most common areas of metastasis are the bone and pelvic lymph nodes. The prognosis of prostate cancer is mainly determined by the status of metastases. The presence and the localization of metastases affects treatment planning. In our cases, we presented some examples of uncommon sites of metastases such as the brain, adrenal glands, penis and orbit. Improvements in imaging techniques, such as 68Ga PSMA PET/CT have led to the possibility to make more determi nation of rare metastase sites in prostate cancer patients.