A Comprehensive Analysis of Volumetric 68Ga-PSMA PET/CT Parameters, Clinical and Histopathologic Features: Evaluation of the Predictive Role.

Objectives: To evaluate the relationships between volumetric 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) parameters, Gleason score (GS), prostate-specific antigen (PSA) levels, histopathological data, and metastatic status in newly diagnosed prostate cancer (PCa) patients and to assess the predictive factors for progression despite treatment. Methods: A total of 78 newly diagnosed patients with PCa who had 68Ga-PSMA PET/CT scans were included. Clinical parameters, histopathological data, and metastatic status were documented, and volumetric parameters of primary prostate lesions were measured. All obtained data were compared statistically. Results: Primary prostate tumor maximum standardized uptake value (SUVmax) and GS were significantly related to serum PSA levels (p<0.05). PSA levels and SUVmax values were significantly higher in patients with lymph node metastases than in those without. GS was found to be significantly increased in metastatic patients. PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA of the primary lesion had a significant relationship with PSA value, GS, and regional lymph node metastases. Receiver operating characteristic analysis, conducted in patients with metastatic and localized disease, identified the cutoff value for SUVmax as 10.85. According to the results of the logistic regression analysis, PSMA-TV was found to be a predictive factor for progression despite treatment. Conclusion: 68Ga-PSMA PET/CT remains an invaluable imaging modality that should be considered first in PCa staging because of its superior compatibility with clinical and histopathologic data. The importance of this method goes beyond diagnostic accuracy; it also extends into the predictive domain, where the PSMA-TV value of primary prostate lesions is a potential predictor of treatment efficacy. This information is valuable for personalizing patient treatment, improving prognostic accuracy, and predicting clinical outcomes.

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.

Development of a Radiolabeled Folate-Mediated Drug Delivery System for Effective Delivery of Docetaxel.

Many preclinical studies are carried out with the aim of developing new formulations for the effective delivery of taxane class drugs, one of the most important anticancer drugs used clinically today. In this study, a radiolabeled folate-mediated solid lipid magnetic nanoparticle (SLMNP) system was developed by loading superparamagnetic iron oxide nanoparticles (MNP) and docetaxel (DTX) into the solid lipid nanoparticles as a drug delivery system that will function both in cancer treatment and diagnosis. For this purpose, first, SLMNP was synthesized by the hot homogenization method, and the surface of the particles was modified with a folate derivative to carry the particles to tissues with folate receptors. The synthesized magnetic solid lipid nanoparticles were loaded with DTX, and then radiolabeling was carried out with technetium-99 m (99mTc-DTX-SLMNP). Structural characteristics of these nanoparticles were determined by characterization methods. According to the TEM images of MNPs, SLN, and SLMNPs, MNPs were observed between 25and 35 nm, SLNs between 400 and 500 nm, and SLMNPs between 350 and 450 nm. The drug entrapment efficiency of SLMNPs loaded with DTX was found to be 19%, and the percentage efficiency of radiolabeling was found to be 98.0 ± 2.0%. The biological behavior of this radiolabeled system was investigated in vitro and in vivo. Folate receptor-positive SKOV-3 and folate receptor-negative A549 cancer cell lines were studied. The IC50 values of DTX-SLMNP in SKOV-3 and A549 cells were 50.21 and 172.27 µM at 48 h, respectively. Gamma camera imaging studies of 99mTc-DTX-SLMNP and magnetically applied 99mTc-DTX-SLMNP compounds were performed on tumor-bearing CD-1 nude mice. The uptake in the folate receptor-positive tumor region was higher than that in the folate receptor negative tumor region. We proposed that the drug delivery system we prepared in this study be evaluated for preclinical studies of new drug carrier formulations of the taxane class of anticancer drugs.

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.

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.

Thymoquinone Glucuronide Conjugated Magnetic Nanoparticle for Bimodal Imaging and Treatment of Cancer as a Novel Theranostic Platform.

BACKGROUND: Theranostic oncology combines therapy and diagnosis and is a new field of medicine that specifically targets the disease by using targeted molecules to destroy the cancerous cells without damaging the surrounding healthy tissues. OBJECTIVE: We aimed to develop a tool that exploits enzymatic TQ release from glucuronide (G) for the imaging and treatment of lung cancer. We added magnetic nanoparticles (MNP) to enable magnetic hyperthermia and MRI, as well as 131I to enable SPECT imaging and radionuclide therapy. METHODS: A glucuronide derivative of thymoquinone (TQG) was enzymatically synthesized and conjugated with the synthesized MNP and then radioiodinated with 131I. New Zealand white rabbits were used in SPECT and MRI studies, while tumor modeling studies were performed on 6-7- week-old nude mice utilized with bioluminescence imaging. RESULTS: Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectra confirmed the expected structures of TQG. The dimensions of nanoparticles were below 10 nm and they had rather polyhedral shapes. Nanoparticles were radioiodinated with 131I with over 95% yield. In imaging studies, in xenograft models, tumor volume was significantly reduced in TQGMNP-treated mice but not in non-treated mice. Among mice treated intravenously with TQGMNP, xenograft tumor models disappeared after 10 and 15 days, respectively. CONCLUSION: Our findings suggest that TQGMNP in solid, semi-solid and liquid formulations can be developed using different radiolabeling nuclides for applications in multimodality imaging (SPECT and MRI). By altering the characteristics of radionuclides, TQGMNP may ultimately be used not only for diagnosis but also for the treatment of various cancers as an in vitro diagnostic kit for the diagnosis of beta glucuronidase-rich cancers.

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo.

BACKGROUND: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). METHODS: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. RESULTS: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. CONCLUSION: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

Synthesis, characterization and radiolabeling of folic acid modified nanostructured lipid carriers as a contrast agent and drug delivery system.

Nanostructured lipid carriers (NLCs) are the new generation of solid lipid drug delivery systems. Their suitability as contrast agents for gamma scintigraphy is an attracting major attention. The aim of current study was to prepare surface modified nanostructured lipid carrier system for paclitaxel (PTX) with active targeting and imaging functions. In accordance with the purpose of study, PTX loaded nanostructured lipid carriers (NLCs) prepared, modified with a folate derivative and radiolabeled with technetium-99m tricarbonyl complex (99mTc(CO)3+). Cellular incorporation ratios of radiolabeled nanoparticles (99mTc(CO)3-PTX-NLC) were investigated in vitro on three cancer cell lines. Additionally in vivo animal studies conducted to evaluate biological behavior of 99mTc(CO)3-PTX-NLC on female Wistar Albino rats. Biodistribution results showed that the folate derivative modified 99mTc(CO)3-PTX-NLC had considerably higher uptake in folate receptor positive organs. The data obtained from present study could be useful in the design of biodegradable drug carriers of PTX and folate receptor based tumor imaging agents.

Samarium-153 therapy for prostate cancer: the evaluation of urine activity, staff exposure and dose rate from patients.

The aim of this study was to determine the excretion of Samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP) in urine and to calculate the dose rate of its retention in the body as a function of time and the dose received by the skin of laboratory staff's finger. Urine samples were collected from 11 patients after intravenous injection of (153)Sm-EDTMP. The measurements of dose rate were performed. Thermoluminescent dosemeters were used for absorbed dose measurements. Effective half-lives that were calculated from urine sample measurements were found as 7.1±3 h within the first 24 h. Whole body dose rates before collecting urine of patients were 60.0 ± 15.7 µSv h(-1) for within 1 h following (153)Sm-EDTMP administration. The highest finger radiation dose is to the right-hand thumb (3.8 ± 2 mGy). The results of the study imply that patients who recieved (153)Sm-EDTMP therapy should be kept a minumum of 8 h in an isolated room at hospital and that one staff should give therapy at most two patients per week.

The evaluation of urine activity and external dose rate from patients receiving radioiodine therapy for thyroid cancer.

The aim of this study was to determine the external dose rate of iodine retention as a function of time in the bodies of thyroid cancer patients during their isolation period in the hospital. Urine samples were collected at 6th, 12th, 18th, 24th h and 2nd, 3rd, 4th, 5th d from 83 patients after oral administration of (131)I and counted. The external dose rates were also simultaneously determined at the same time points. Then, it was expressed as retained radioiodine body activity versus dose rate. Effective half life calculated from urine sample measurements was found as 18.4±1.8 h within the first 24 h and 64±2.7 h between 48 and 120 h. According to this results, the external dose rate (<20 µSv h(-1)), which patients could be discharged, was achieved after 48 h for 3700 and 5550 MBq, and after 72 h for 7400 MBq of (131)I treatments.

Effects of 99mTc-MIBI and 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements.

OBJECTIVE: Nuclear medicine procedures are often performed in close-time proximity to bone densitometry studies. The purpose of this study was to determine the effects of Tc-hexakis-2-methoxyisobutyl isonitrile (MIBI) and Tc-methylene diphosphonate (MDP) on the accuracy of bone mineral density (BMD) measurements performed using dual-energy X-ray density. METHODS: The effect of a diagnostic dose of Tc-MIBI on BMD estimations in the lumbar spine and the left total hip was assessed in 30 patients (19 female, 11 male; mean age: 55.5+/-10.5 years) by using a Lunar DPX-NT scanner. Thirty patients, admitted to the nuclear medicine department for bone scintigraphy (15 female, 15 male; mean age: 56+/-15.92 years), were included into the study. Each patient underwent dual-energy X-ray density assessment for which a Lunar DPX-NT scanner was used before and 2 h after intravenous injection of Tc-MDP (925 MBq) and Tc-MIBI (1110 MBq). BMD measurements were calculated from lumbar spine (including L2-4) and left hip (including femoral neck, trochanter, and total hip). For statistical analysis, the Wilcoxon test was used and a P value of less than 0.05 was accepted as statistically significant. RESULTS: According to Wilcoxon's statistical test, we found extremely significant changes on the measured BMD, T-score, before and 2 h after the injection of Tc-MIBI for lumbar spine and left hip in 30 patients. We found statistically significant decrement on measured BMD from lumbar spine and trochanter before and 2 h after the injection of Tc-MDP. Although MDP BMD values in femoral neck and total hip were decreased after the injection of Tc-99m, they did not reach a statistically significant value. The comparison of pre-T-score and post-T-score values showed a statistically significant decrease after the injection for only L2-4 lumbar spine (P = 0.002), but left hip of pre-T-score and post-T-score values did not reach a statistically significant value. CONCLUSION: In this study, it was determined that measured BMD values are decreased in lumbar spine for all patients. The magnitude of the effect is dependent on the location of the activity. We assume that some radioactivity from Tc is counted by the densitometer's detector, thus resulting in a decrease in the measured BMD. Scintigraphy and bone densitometry should be performed on different days to avoid artifactual reduction in BMD measurements.