Development of 99mTc-SDP-choline SPECT radiopharmaceutical for imaging of cerebrovascular diseases.

Cerebrovascular diseases are known as serious public health problem worldwide, which can be addressed more precisely through molecular imaging of non-functional brain cells. CDP-choline is an active cerebrovascular chemotherapeutic agent that can be used for diagnosis of cerebrovascular diseases post radiolabeling with γ-emitter radioisotopes. In this study we developed 99mTc labeled CDP-choline for imaging of cerebrovascular diseases particularly alzheimer, stroke, and parkinson's diseases. The radiosynthesis reaction resulted 97.47±2.34% radiochemical with promising stability, that is, >95% up to 6 h in blood serum. The biodistribution study in healthy mice revealed non-accumulated uptake of radiochemical in key body organs; in brain it was 8.59±1.11% ID/g at 1h post-injection which washed-out leaving behind 0.87±0.61% ID/g at 24 h post-injection. The over-all data revealed the 99mTc-CDP-choline could be a good candidate for further imaging investigations in diseased animal model.

177Lu-DOTA-coupled minigastrin peptides: promising theranostic agents in neuroendocrine cancers.

Treatment with radionuclide labeled regulatory peptides is a promising tool in the management of patients with inoperable receptor positive neuroendocrine tumors. Peptide receptor lutetium-177 radionuclide therapy currently has gained ample attention due to high specific accumulation of regulatory peptides at tumor cell surface and promising characteristics of ß- and γ-energy photons of lutetium-177 radionuclide. In this study gastrin peptides analogues were labeled with lutetium-177 by subsequent mixing of 177LuCl3 (~ 185 MBq), ammonium acetate buffer of 5 pH, gentistic acid, aqueous solution of gastrin peptide analogues (1 mg/mL) and heating the reaction mixture at 98 °C which resulted in high radiochemical yield (> 96%). Chromatographic analysis was carried out to analyze the radiochemical purity. The shelf life and serum stability results showed the labeled peptides are sufficiently stable up to 4-h. Glomerular filtration rate study results showed moderate filtration through kidneys. The GFR values of 177Lu-MGCL2 and 177Lu-MGCL4 was noted 48 mL/min and 45 mL/min, respectively. Biodistribution and scintigraphy study using rat and rabbit models showed minimal non-target accumulation, moderate uptake by liver and kidneys. The promising radiochemical yield, stability, GFR values and biodistribution results of 177Lu-MGCL2 & 4 indicate, the agents can be tested clinically for PRRT procedures.

Evaluation of 99mTc-sulfadiazine as Bacillus microorganisms infection imaging agent using animal model.

Bacterial infection is one of the vital sources of morbidity and mortality. The development of single photon emission computed tomography (SPECT) radiotracer agents using antibiotics, for targeting in-vivo bacteria, helps in antibiotic dose calibration, targeted infection therapy and reduction in mortality rate. The aim of this study was to appraised 99mTc-labeling sulfadiazine as a radiopharmaceutical for bacillus infections imaging. Radiolabeling of sulfadiazine with technetium-99m was carried out by subsequent addition of 1.5 mL aqueous solution of sulfadiazine (1mg/mL), 120µg stannous tartrate, gentistic acid as stabilizing agent and 185 MBq normal saline solution of 99mTcO4-1 (pertechnetate) at pH = 5. The reaction mixture was incubated for 40 min at room temperature with light stirring. The quality control analysis (ITLC-SG and paper chromatography analysis) revealed ~ 98% labeling yield. Biodistribution and scintigraphic study was carried using bacillus bacterial infection induced New Zealand white rabbits. Due to the ease of 99mTc-sulfadiazine conjugation method, high labeling efficiency, shelf stability (>95% up to 6h), blood serum stability (~90% up to 6h) and high uptake in the infected muscle (T/NT =2.21 at 1H), 99mTc-SDZ could be used as radiopharmaceutical of choice for further pre-clinical and clinical studies.

99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

The radiolabeled drug 99m Tc-tazobactam (99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues.

Radiolabeling of benzylpenicillin with lutetium-177: Quality control and biodistribution study to develop theranostic infection imaging agent.

Benzylpenicillin acts through binding with beta-lactamase enzyme and inhibiting the bacterial cell wall biosynthesis. Therefore, the radiolabeling of benzylpenicillin with lutetium-177 is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiolabeling of benzylpenicillin resulted ~93% radiochemical yield at optimized reaction conditions. Radiochemical purity analysis was tested with the help of Whatman No. 2 paper and instant thin layer chromatography. Biodistribution study with healthy New Zeeland white rabbit revealed moderate accumulation in different organs. Kidneys are the major organs, showed not more than 4.57±0.89% injected dose per gram organ (ID/gm organ) at 1 h time point and 3.48±1.11% ID/gm organ at 6 h time point. The accumulation of tracer agent in liver was found in the range of 7.42±2.42% to 9.09±2.76 ID/gm organ. The glomerular filtration rate studies revealed rapid clearance - omitting the chance of nephrotoxicity. The radiolabeling yield, biodistribution and glomerular filtration rate results revealed 177Lu-benzylpencillin could be a potential candidate to diagnose the deep-seated bacterial infection.

(177) Lu-5-Fluorouracil a potential theranostic radiopharmaceutical: radiosynthesis, quality control, biodistribution, and scintigraphy.

The aim of this study is to develop (177) Lu-5-Flourouracil as a potential cancer therapeutic radiopharmaceutical. 5-Flourouracil (5-FU) is widely accepted as an anticancer drug of broad spectrum fame. The labeling of 5-FU was carried out at different set of experimental conditions using high specific activity of (177) LuCl3 . The optimum conditions for maximum radiochemical yield was set: 5-FU (5 mg), (177) LuCl3 (185 MBq), diethylenetriaminepentaacetic acid (10 µg), reaction volume (2 mL), pH (5.5), temperature (80°C), and reaction time (20 min). The radiochemical labeling was assessed with Whatman No. 2 paper, instant thin layer chromatographic, and radio-HPLC, which revealed >94% labeling results with sufficient stability up to 6 h. Serum stability study also showed (177) Lu-5-FU promising stability. Biodistribution study in normal rats and rabbits showed liver, stomach, kidney, and heart as area of increased tracer accumulation just after injection, which decreased to 1.4%, 0.4%, 0.2%, and 0.39% ID/g, respectively, after 72 h. Glomerular filtration rate and cytotoxicity study results of (177) Lu-5-FU showed it had no adverse effect on renal function and nontoxic to blood cells. The promising characteristics of (177) Lu-5-FU, that is, clever elimination from kidney and nontoxic nature toward blood cells make it the radiopharmaceutical for further testing in patients for therapeutic purposes.

Preparation of (99m)Tc-labelled methotraxate by a direct labeling technique as a potential diagnostic agent for breast cancer and preliminary clinical results.

Methotrexate (MTX) is being used in clinical oncology for the treatment of a wide variety of cancers. The aim of the present study was to label directly MTX with (99m)Tc by using Sn/pyrophosphate as reducing agent and to use this labeled compound as a potential anticancer radiopharmaceutical for breast cancer imaging. We studied the labeling efficiency of the (99m)Tc-MTX compound by paper chromatography and instant thin layer chromatography (ITLC) in acetone and saline and found it to be more than 95%. In vitro stability of labeled MTX in serum was studied up to 5h. Partition coefficient in n-octanol and saline indicated that the labeled radiopharmaceutical was hydrophilic. We then tested (99m)Tc-MTX in 5 breast cancer female patients. Protein bound (99m)Tc-MTX showed rapid clearance from blood. The biodistibution data suggested that (99m)Tc-MTX was cleared by the kidneys and the liver. Patients ' data also showed highly significant uptake of (99m)Tc-MTX in breast cancer. In conclusion, this study indicated that (99m)Tc-MTX may be used as a potential diagnostic agent for breast cancer patients imaging and may show treatment efficiency in case MTX is to be used for treatment.

Preperation of (99m)Tc labeled 5-fluorouracil as a potential diagnostic agent in advanced breast cancer: first clinical trial.

The chemotherapeutic drug 5-fluorouracil (5FU) is used for treatment of various types of cancers. The present study was conducted to evaluate the potential of this drug as a diagnostic radiopharmaceutical in advanced breast cancer. We have labeled 5FU by using the stannous chloride reduction method with 555MBq of technetium-99m ((99m)Tc). The (99m)Tc-5FU was injected intravenously in 4 patients having advanced breast cancer. Dynamic and static images were taken at various time intervals till 2h. Whole body images were used to calculate the percentage of the injected dose, in each organ. Target to non target ratio was calculated to find out the optimum time for imaging. In conclusion, our study showed that (99m)Tc-5FU was a promising agent for diagnosing advanced breast cancer with optimum visualization at 1h.

A Review on Nuclear Imaging as a Promising Modality for Efficient Diagnosis of Tuberculosis.

Tuberculosis (TB) is an infectious disease, which has been declared as a global health issue by the World Health Organization in 1993. Due to the complex pathophysiology of Mycobacterium tuberculosis, it remains a global threat. This article reviews the conventional diagnostic modalities for tuberculosis, their limitations to detect latent TB, multiple drug resistant-TB, human immunodeficiency virus co-infected TB lesions, and TB in children. Moreover, this review illustrates the importance of nuclear medicine imaging for early, non-invasive diagnosis of TB, to detect disease stages and to monitor therapy response. Single-photon emission computed tomography and positron emission tomography with their particular radionuclides are now extensively being used for a thorough assessment of TB.

Occult Bone Metastases From Hepatocellular Carcinoma Detected on 68Ga-PMSA PET/CT.

ABSTRACT: 68Ga-PSMA is an excellent radiotracer for both staging and detection of recurrence in prostate cancer, but it can also be useful in other solid tumors due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of an 82-year-old man with hepatocellular carcinoma who presented with rising tumor marker but stable CT findings 6 months after transarterial chemoembolization. 68Ga-PSMA PET/CT showed high PSMA-expressing hyperneovascular hepatic lesions (primary tumor), additional multifocal hepatic lesions, and with unexpected multiple bone metastases. 68Ga-PSMA expression in hepatocellular carcinoma can influence patient management and potentially guide radionuclide legend therapy.

The clinical effectiveness of reconstructing 18F-sodium fluoride PET/CT bone using Bayesian penalized likelihood algorithm for evaluation of metastatic bone disease in obese patients.

OBJECTIVE: A new Bayesian penalized likelihood reconstruction algorithm for positron emission tomography (PET) (Q.Clear) is now in clinical use for fludeoxyglucose (FDG) PET/CT. However, experience with non-FDG tracers and in special patient populations is limited. This pilot study aims to compare Q.Clear to standard PET reconstructions for 18F sodium fluoride (18F-NaF) PET in obese patients. METHODS: 30 whole body 18F-NaF PET/CT scans (10 patients with BMI 30-40 Kg/m2 and 20 patients with BMI >40 Kg/m2) and a NEMA image quality phantom scans were analyzed using ordered subset expectation maximization (OSEM) and Q.Clear reconstructions methods with B400, 600, 800 and 1000. The images were assessed for overall image quality (IQ), noise level, background soft tissue, and lesion detectability, contrast recovery (CR), background variability (BV) and contrast-to-noise ratio (CNR) for both algorithms. RESULTS: CNR for clinical cases was higher for Q.Clear than OSEM (p < 0.05). Mean CNR for OSEM was (21.62 ± 8.9), and for Q.Clear B400 (31.82 ± 14.6), B600 (35.54 ± 14.9), B800 (39.81 ± 16.1), and B1000 (40.9 ± 17.8). As the ß value increased the CNR increased in all clinical cases. B600 was the preferred ß value for reconstruction in obese patients. The phantom study showed Q.Clear reconstructions gave lower CR and lower BV than OSEM. The CNR for all spheres was significantly higher for Q.Clear (independent of ß) than OSEM (p < 0.05), suggesting superiority of Q.Clear. CONCLUSION: This pilot clinical study shows that Q.Clear reconstruction algorithm improves overall IQ of 18F-NaF PET in obese patients. Our clinical and phantom measurement results demonstrate improved CNR and reduced BV when using Q.Clear. A ß value of 600 is preferred for reconstructing 18F-NaF PET/CT with Q.Clear in obese patients. ADVANCES IN KNOWLEDGE: 18F-NaF PET/CT is less susceptible to artifacts induced by body habitus. Bayesian penalized likelihood reconstruction with18F-NaF PET improves overall IQ in obese patients.

Textitis as Seen on 18F-NaF Imaging Using an Ultra-High-Resolution Positron Emission Mammography Scanner.

Textitis is a new term used to refer to the degenerative-strain osteoarthritis that comes from excessive use of a smart phone. 18F-NaF is increasingly used in diagnosing skeletal pain that is not identified on radiographs. We report a case of a 26-y-old woman with left breast cancer referred for 18F-NaF PET/CT, who was complaining of right thumb and wrist pain. Findings were negative for bone secondaries. Dedicated hands views were acquired on a positron emission mammography scanner and showed focal uptake at the first carpometacarpal and second metacarpophalangeal joints. On the basis of the strong history, the findings were likely due to active arthritic changes caused by repetitive strain injury from excessive text messaging.

Incremental Value of Post Diuretic 68Ga-PSMA-11 PET-CT in Characterization of Indeterminate lLesions in Prostate Cancer.

OBJECTIVE: The aim of current study is to evaluate the role of diuretic assisted 68Ga-PSMA PET-CT, on image quality and clinical interpretation of indeterminate/equivocal lesions in pre-Lasix imaging of Prostate cancer. MATERIALS AND METHODS: Forty-five patients underwent baseline 68Ga-PSMA-11 scan 45-60 minutes post tracer injection followed by post Lasix study after ±15 minutes. The contrast to noise ratios (CNR), noise and SUVmax were determined for the focal uptakes in both pre and post Lasix images. All continuous variables were expressed as mean ± SD. Images were assessed by two experienced physicians in order to  evaluate lesion detectability and delineations that have an impact on clinical interpretation. RESULTS: Of total 45 patients, 12/45 (27%) showed unremarkable scan along with 33/45 (73%) showing metastases. Sixteen out of 45 (36%) of the metastatic scans showed indeterminate/equivocal lesions. In these cases, post Lasix study showed false negative findings in 7/45 (16%), better delineation of lesions 10/45 (22%), better confidence towards reporting lesions as abnormal in 5/45 (11%) with an overall 11/45 (24%) of the cases who showed increase in the number of the lesions after the Lasix study. The overall CNR was evaluated using Wilcoxon Rank test (p-value = 0.02) which suggested significant improved ratios in the post-Lasix imaging by 49.6%±24.5. There was a substantial agreement (k =0.76) between the physicians when comparing the lesion clarity and delineation in post Lasix images. The average score for physician one and two being 2.4 ±0.71 and 2.53±0.52 respectively. CONCLUSION: Post diuretic 68Ga-PSMA imaging at ± 15 minutes clears the unwanted activity in the urinary tract which in turn improves the contrast to noise ratios. Thus leading to decline in false positive findings, improved diagnostic certainty of physician and better detection of indeterminate lesions in 68Ga-PSMA imaging.

Significance of 18F-FDG PET/CT in Characterization of Equivocal Lesions in High-Risk Testicular Carcinoma in Restaging Setting.

OBJECTIVES: The present study aims to evaluate the role of Positron emission tomography (PET) -computed tomography (CT) with 18F-fluorodeoxyglucose (18F-FDG) in the restaging of high-risk testicular cancer. METHODS: Forty-five patients (mean age of 38.1±11.3 years and range 23-81 years) with testicular carcinoma, underwent 18F-FDG PET-CT during their clinical course were prospectively selected. PET positivity was defined as a site of abnormal 18F-FDG uptake in tissue histologically proven or clinically or radiographically suspected to represent tissue involvement. The sites of disease were characterized as either nodal or extranodal. All patients were followed-up for at least 12 months with a diagnostic and/or functional imaging modality. RESULTS: Of the 45 patients 38 (84%) patient presented with seminoma and 7 (16%) were Non-seminomatous germ cell tumors. Analysis of secondary disease spectrum showed nodal involvement in 65%, osseous involvement in 23% and mixed visceral/soft tissue lesions in 12% of patients. Nineteen (42%) were negative for any metastatic disease. All negative patients remain disease free in the follow-up of one year. Out of the positive 26/45 patients, PET-CT showed progressive disease in 3/26, stable disease 1/26 and partial response in 2/26 and complete metabolic resolution in 20/26 patients. 18F-FDG PET-CT was able to characterize all patients leading to significant change of primary decision of wait and watch to go for treatment and vice versa. CONCLUSION: 18F-FDG PET-CT scan is potentially an excellent tool for characterization of equivocal lesions on CT scan in the restaging settings and follow up of high-risk testicular cancer patients.

Synthesis and Biodistribution Study of Biocompatible 198Au Nanoparticles by use of Arabinoxylan as Reducing and Stabilizing Agent.

Radioactive gold-198 is a useful diagnostic and therapeutic agent. Gold in the form of nanoparticles possesses even more exciting properties. This work aimed at arabinoxylan-mediated synthesis and biodistribution study of radioactive gold nanoparticles (198AuNPs). The particles were synthesized by mixing suspension of arabinoxylan with H198AuCl4 without use of any additional reducing and stabilizing agents. An aqueous suspension of arabinoxylan was added to a H198AuCl4 solution, which resulted in reduction of Au3+ to 198AuNPs. Biodistribution was studied in vitro and in rabbit. The particles having exceptional stability were readily formed. Highest radioactivity was recorded in spleen after 3 h followed by liver, heart, kidney, and lungs after i.v. administration. After 24 h, the activity was not detectable in the spleen; it accumulated in the liver. However, after oral administration, the activity mainly accumulated in the colon. In serum proteins, the distribution was α1-globulin 6.5%, α2-globulin ~ 2%, ß-globulin ~ 1%, γ-globulin 0.7%, and albumin 0.7% of the administered dose. This indicates a low protein binding implying high bioavailability of the particles. The cytotoxicity study showed that the particles were inactive against HeLa cell line and Agrobacteriumtumefaciens. Highly stable 198AuNPs reported in this work have the potential for targeting the colon. They show affinity for globulins, the property that can be used in the study of the immune system.

Correction to: Synthesis and Biodistribution Study of Biocompatible 198Au Nanoparticles by use of Arabinoxylan as Reducing and Stabilizing Agent.

The original version of this article unfortunately contained a mistake.

Klippel-Trenaunay syndrome.

Klippel-Trenaunay Syndrome (KTS) is a rare, congenital, vascular disorder affecting one or more limbs. Originally, it was defined as a triad including port wine stain, varicose veins and bony and soft tissue hypertrophy. We present a case of a 20-year-old female who walked with a limp. Because of swelling of right leg she was sent for Doppler study which picked up dilated arteries and increased blood flow velocity. The impression of KTS was further strengthened by unique nuclear medicine and radiological findings.

Immune Checkpoint Inhibitors (Nivolumab)-Induced Enterocolitis Demonstrated on 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Nivolumab, an immune checkpoint inhibitor, is a humanized anti-programmed death-1 monoclonal antibody that is used for the treatment of various cancers after second-line chemotherapy. We report a 23-year-old male with relapsed Hodgkin's lymphoma Stage IV treated with nivolumab. After 3 months of treatment, he developed watery diarrhea and cramping abdominal pain. Follow-up positron emission tomography-computed tomography scan showed complete metabolic resolution of the disease; however, there is bowel wall thickening and colonic distension with corresponding increased fluorodeoxyglucose uptake. These findings are related to immune-related adverse event associated with nivolumab treatment, i.e., secondary enterocolitis. These adverse events can be successfully treated if timely and appropriately diagnosed.

The Established Nuclear Medicine Modalities for Imaging of Bone Metastases.

BACKGROUND: The skeleton is one of the frequent site of metastases in advanced cancer. Prostate, breast and renal cancers mostly metastasize to bone. DISCUSSION: Malignant tumors lead to significant morbidity and mortality. Identification of bone lesions is a crucial step in diagnosis of disease at early stage, monitoring of disease progression and evaluation of therapy. Diagnosis of cancer metastases is based on uptake of bone-targeted radioactive tracer at different bone remodeling sites. CONCLUSION: This manuscript summarizes already established and evolving nuclear medicine modalities (e.g. bone scan, SPECT, SPECT/CT, PET, PET/CT) for imaging of bone metastases.

225Ac Prostate-Specific Membrane Antigen Posttherapy α Imaging: Comparing 2 and 3 Photopeaks.

Ac-based PSMA-targeted therapy has emerged as promising agent for the treatment of metastatic castration-resistant prostate cancer. Posttherapy image is used for tracer localization and dosimetry. Prior 2 photopeaks of 440 and 218 KeV were reported for posttherapy imaging. Our study of gamma ray spectrum, phantom, and clinical images show that imaging with 3 major photopeaks of 78, 218, and 440 KeV gives better quality images, high count statistics, and higher number of lesion delineations. It is therefore suggested that posttherapy imaging may be carried out using 3 major abundant photopeaks.