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.

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.

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.

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.

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.

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.

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.

Tc-99m HDP Single Photon Emission Computed Tomography/Computed Tomography in Stress Fracture of Base of Metatarsal Bone.

Proximal metatarsal stress fractures are common at base of the second metatarsal, typically seen in repetitive impact athletes, dancers, and those with cavus feet. It is caused by increased bone resorption rather than formation in a state of abrupt increased physical activity or intensity, leading to repetitive microfractures and eventually stress fracture. It is characterized by swelling and tenderness of a prolonged duration. We report a case of a 40-year-old female having left foot pain diagnosed with stress fracture on Tc-99m HDP single-photon emission computed tomography (SPECT)-CT. We emphasize the use of SPECT/CT in allocating active source of pain in the feet.

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.

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.

Susceptibility of 99mTc-Ciprofloxacin for Common Infection Causing Bacterial Strains Isolated from Clinical Samples: an In Vitro and In Vivo Study.

99mTc-ciprofloxacin scintigraphy is useful in the detection of gram-positive and gram-negative bacterial infections and also for differentiating the infection from aseptic inflammation. However, due to growing bacterial resistance to antibiotics, the 99mTc-ciprofloxacin no longer can be effective in broad-spectrum infection imaging as it is gradually losing specificity. In this study, we are presenting our findings regarding the in vitro and in vivo susceptibility of 99mTc-ciprofloxacin for multi-drug-resistant Staphylococcus aurous, Escherichia coli, and Pseudomonas aeruginosa bacterial strains which were isolated from clinical samples. The results of radiosynthesis of 99mTc-ciprofloxacin showed more the 95% radiochemical purity and less than 5% radioactive impurities. In vitro 99mTc-ciprofloxacin susceptibility test showed that E. coli offered more resistant to 99mTc-ciprofloxacin as compared to S. aurous and P. aeruginosa. In vivo study using bacterial infection induced rabbit model also revealed lowest uptake by E. coli lesion. The T/NT values were obtained 1.96 ± 0.15 in the case of E. coli; 2.81 ± 0.51 in the case of S. aurous; and 2.32 ± 0.66 in the case of P. aeruginosa at 4 h post-injection. The SPECT infection imaging of S. aurous, E. coli, and P. aeruginosa bacterial infection induced rabbit models also indicated the clear accumulation in S. aurous and P. aeruginosa lesions while negligible uptake by E. coli lesion further verify the in vitro and in vivo susceptibility profile. On the bases of the results obtained, the 99mTc-ciprofloxacin showed selective and poor broad spectrum SPECT infection imaging.

Gynaecological Cancer Diagnostics: 99mTc-Cisplatin Complex as a Future Approach for Early, Prompt and Efficient Diagnosis of Gynaecological Cancer.

BACKGROUND: Gynaecological cancers (GCCa) are common and have a significant mortality rate all over the world. Early diagnosis of cancer can play a key role in the treatment and survival of a patient. Identification, staging, treatment, and monitoring of gynaecological malignancies is being done successfully by nuclear medicines. DISCUSSION: Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) centered imaging techniques are being developed for use in patients with GCCa as a diagnostic tool. The present work elucidates several clinical studies on the use of radiopharmaceuticals, based on their effectiveness, in the early detection and management of GCCa. It also highlights the importance of reconsidering the biology for nuclear imaging as a future modality for early, rapid and efficient diagnosis of gynecological cancers. This comprehensive review is a part of our study designed to detect gynaecological cancers at an early stage using radionuclide complex, 99m Tc-Cisplatin. CONCLUSION: This article summarizes the significance of radioscintigraphy such as single-photon emission computed tomography (SPECT) and PET for identification of GCCa in the experimental humans and animals.

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.

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.