Fibroblast Activation Protein Inhibitor-Based Radionuclide Therapies: Current Status and Future Directions.

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer cells develop beside and depend on the complex tumor microenvironment. Cancer-associated fibroblasts, with their complex interaction with tumor and immune cells, are involved in various steps of tumorigenesis, such as growth, invasion, metastasis, and treatment resistance. Prooncogenic cancer-associated fibroblasts emerged as attractive therapeutic targets. However, clinical trials have achieved suboptimal success. Fibroblast activation protein (FAP) inhibitor-based molecular imaging has shown encouraging results in cancer diagnosis, making them innovative targets for FAP inhibitor-based radionuclide therapies. This review summarizes the results of preclinical and clinical FAP-based radionuclide therapies. We will describe advances and FAP molecule modification in this novel therapy, as well as its dosimetry, safety profile, and efficacy. This summary may guide future research directions and optimize clinical decision-making in this emerging field.

Insight into Tumor Hypoxia: Radionuclide-based Biomarker as Diagnostic Tools.

The radiolabeled tracers have been extensively utilized to access various physiological and pathological conditions non-invasively, such as cancers, inflammation, and organ-specific imaging. These tracers demonstrate and study tumor hypoxia in several malignancies. Hypoxia is commonly seen in solid tumors. Tumor Hypoxia is a non-physiological condition of reduced oxygen concentration in the tumor. Hypoxia is associated with adverse outcomes such as treatment resistance and metastases in solid tumors. Tumor hypoxia may result in resistance to radiation therapy and chemotherapy, leading to a poor prognosis. It is one of the clinically paramount factors in treatment planning. Various chemical scaffolds are labeled with compatible radioisotopes for imaging hypoxia by Single-photon emission computed tomography (SPECT) and Positron emission tomography (PET). Radionuclides, such as [18F]Flourine, [99mTc]Technetium, [131I]Iodine, [124I] Iodine, and [64Cu]Copper are used for incorporation into different chemical scaffolds.Among them, [18F]Flourine and [64Cu]Copper tagged radiopharmaceuticals are most explored, such as [18F]FMISO, [18F]FAZA, [18F]FETNIM, and N4-methyl thiosemicarbazone [64Cu][Cu (ATSM)]. Some of the promising scaffolds for imaging hypoxia are [18F]EF1, [18F]EF5, [18F]EF3, and [18F]HX4. This review is focused on developing radiochemistry routes to synthesize different radiopharmaceuticals for imaging hypoxia in clinical and preclinical studies, as described in the literature. The chemist and radiochemist exerted enormous efforts to overcome these obstacles. They have successfully formulated multiple radiopharmaceuticals for hypoxia imaging. Radionuclide incorporation in high selectivity and efficiency (radiochemical yield, specific activity, purity, and radio-scalability) is a need for application perspective. Versatile chemistry, including nucleophilic and electrophilic substitutions, allows the direct or indirect introduction of radioisotopes into molecules of interest. This review will discuss the chemical routes for synthesizing and utilizing different precursors for radiolabeling with radionuclides.We will briefly summaries these radio-labeled tracers' application and biological significance.

18 F-FDG PET/CT in Extensive Follicular Dendritic Cell Sarcoma With Response Assessment to Chemotherapy.

ABSTRACT: Follicular dendritic cell sarcoma (FDCS) is a low-grade sarcoma of mesenchymal dendritic cell origin, and it constitutes <0.4% of soft tissue sarcomas. We report a rare case of FDCS in a 32-year-old man. 18 F-FDG PET/CT demonstrated the involvement of cervical, axillary, mediastinal, abdominal, and pelvic groups of lymph nodes and spleen. A cervical lymph node biopsy suggested FDCS. 18 F-FDG PET/CT scan done after 3 cycles of chemotherapy (CHOP regime) revealed a complete metabolic response. This case presents the rarity of extensive presentation and complete response to the CHOP regime.

Extensive Extramedullary Involvement at Presentation in B-Cell Acute Lymphoblastic Leukemia.

ABSTRACT: Extensive extramedullary involvement as presentation is uncommon in pediatric B-cell acute lymphoblastic leukemia. A 7-year-old boy was diagnosed with painless parotid gland enlargement. He had pancytopenia and significantly raised serum lactate dehydrogenase. Fine-needle aspiration cytology from the parotid was suggestive of lymphoid malignancy. Flow cytometry and bone marrow biopsy suggested B-cell acute lymphoblastic leukemia. 18 F-FDG PET/CT revealed extensive bone marrow disease and the involvement of the spleen, pancreas, kidneys, and the parotid, submandibular, and lacrimal glands. He had negligible physiological brain uptake.

Extensive Pleural Involvement in Pediatric T-Cell Lymphoblastic Lymphoma.

Lymphoblastic lymphoma (LBL) is the common non-Hodgkin lymphoma in childhood and adolescence. T-cell LBL (T-LBL) usually manifests with an anterior mediastinal mass and disseminated disease. We present a 12-year-old girl with progressive neck swelling and dyspnea for 1 year. Fluorodeoxyglucose positron-emission tomography/computed tomography done for pretreatment staging unveiled hypermetabolic lymph nodes on both sides of the diaphragm with splenic and bone marrow involvement. Apart from these, there was the extensive involvement of the left pleura. Biopsy and immunohistochemistry revealed T-LBL. The extensive secondary pleural involvement in pediatric T-LBL is rarely seen and needs to be reported.

Robotic computed tomography-guided celiac plexus neurolysis: our experience of technique and outcomes.

Aim: We report the use of robot assistance for computed tomography-guided celiac plexus neurolysis for the first time. Materials & methods: Four patients of upper abdominal cancer with intractable pain despite opioids were positioned prone on the PET-computed tomography scanner, which measured the accurate coordinates for the entry, depth and angle of the target point. The robot positioned its arm over the patient in accordance with the set needle path. The physician manually inserted needle through it and injected 20 ml of 0.75% alcohol after dye confirmation. Results: Significant reduction in pain scores and oral morphine consumption were observed in patients during 3 months follow-up. Conclusion: The robot precisely orients and helps in accurate placement of the needle through the robotic arm.

Outcome of 18f-Fluorodeoxyglucose Positron Emission Tomography (PET)-Directed Resections in Differentiated Thyroid Carcinoma (DTC): Experience in a Developing Country.

The aim of this study was to assess the accuracy of 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET scan) in localizing the disease in differentiated thyroid carcinoma patients undergoing re-operations. This is a retrospective analysis of a prospectively maintained data (December 2007 to December 2016). The patients included had elevated serum thyroglobulin (Tg) levels and negative iodine uptake (TENIS) and planned for re-operation with one or more accessible site of metastasis detected on FDG-PET scan. Clinical details, FDG-PET/CT findings, operative findings, histology, pre-, and post-operative Tg levels were recorded. Thirty-two patients were included. The mean age of the patients was 46.8 ± 15.8 years (M:F = 1:1.6) and mean pre-operative Tg value was 247.6 ± 92.3 ng/ml. FDG-PET disclosed a total of 77 hot spots in these 32 patients, 56 of which were surgically explored and resections performed. Patient- and lesion-based positive predictive value (PPV) of FDG-PET in detecting recurrent/metastatic DTC lesions was 87.5 and 71%, respectively. Remaining cases had granulomatous or nonspecific inflammatory lesions. A total of 12.5% of recurrent DTC patients explored could achieve biochemical cure. All these had disease confined to neck. Remaining patients continued to have high serum Tg level, though it fell substantially in majority of patients. False positive scans are frequent in regions with high prevalence of inflammatory diseases. Hence, FDG-PET directed re-operations should be taken up judiciously.

Skeletal Metastases of Unknown Primary: A Rare Presentation of Carcinoma Pancreas on Fludeoxyglucose Positron Emission Tomography-Computed Tomography.

Skeletal metastases of unknown primary represent skeletal metastases where primary tumors remain obscure. They usually arise from lung and prostate cancer. We present a case of a young male who presented with severe bone pains, weight loss, and generalized weakness. Fludeoxyglucose positron emission tomography-computed tomography reveals extensive skeletal metastases, a mass in the pancreas tail, and other metastatic lesions. He had no liver or lung metastases. This case presents a rare presentation of carcinoma pancreas.

Role of Ga-68 DOTANOC Positron Emission Tomography/ Computed Tomography Scan in Clinical Management of Patients with Neuroendocrine Tumors and its Correlation with Conventional Imaging- Experience in a Tertiary Care Center in India.

Purpose of Study: Aim of the study was to evaluate the role of 68Gallium-DOTANOC positron emission tomography/computed tomography (68Ga-DOTANOC PET/CT), a pan somatostatin receptor (SSTR) analog in the clinical management of patients with neuroendocrine tumors (NETs) and its correlation with conventional imaging. Materials and Methods: We retrospectively evaluated 69 patients of known/suspected NETs who underwent 68Ga-DOTANOC PET/CT scan for tumor localization (n = 15), stage modification (primary staging, n = 26 and restaging, n = 25) and therapy monitoring (n = 3). We also compared PET scan with conventional imaging as reference standard and evaluated the impact of PET/CT in the clinical management of patients. Results: The concordant findings on 68Ga-DOTANOC PET/CT and conventional imaging seen in 33 and discordant in 36 patients. Among discordant group, disease was upstaged in 32 patients; down staged in 3 patients; no stage change in one patient. PET/CT localized primary tumor in 4 patients. Among patients with raised tumor markers (39/69), PET was positive in 29 and negative in 10 patients. Patients were followed for mean duration of 27 months to assess management. We found strong agreement between positive PET and raised tumor markers (Kappa value = 0.8). Sensitivity and specificity of PET/CT for primary tumor localization, stage modification, and therapy monitoring was >90% (P < 0.05). Conclusions: Study shows that DOTANOC, a broad spectrum SSTRs binding peptide labeled with Ga-68 in PET/CT scan is an excellent modality in the management of NETs patients.

Metastatic Urinary Bladder Carcinoma on Palliative Chemotherapy Showing Rapid Progression on Interim Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Bladder cancer (BC) is among the top ten most common cancer types globally. Muscle invasive BC has a high incidence of metastasis. Metastatic BC has a poor prognosis and limited treatment options. Here, we present a middle-aged man with oligometastatic BC, which was treated with palliative chemotherapy. He had significant clinical improvement. However, interim 18F-Fluorodeoxyglucose positron emission tomography/computed tomography demonstrates a rapid disease progression extensive metastasis.

Utero-Ovarian Involvement in Non-Hodgkin's Lymphoma on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: A Case Series and Literature Review.

Lymphomas are common solid malignancies. They are associated with substantial morbidity and mortality. Hodgkin's lymphoma (HL) and Non-HL (NHL) are subtypes of lymphoma. Lymph nodes are the most common site of involvement, though practically any organ may be involved. NHL has preponderance for extranodal involvement. Primary uterine and ovarian NHL is scarce. However, in advanced systemic disease, secondary utero-ovarian involvement may be seen. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a pivotal imaging modality in lymphomas. It abets in pretreatment staging, posttherapy restaging, and surveillance. We present three stage-IV NHL cases with secondary utero-ovarian involvement. FDG PET/CT as a baseline imaging modality established the disease burden and organ involvement.

Port-Site Metastases in Incidentally Detected Carcinoma Gall Bladder: Role of 18F-FDG PET/CT and Patient Outcome.

BACKGROUND: Incidentally detected gall bladder carcinoma (IGBC) is occasionally encountered after cholecystectomy for benign gall bladder disease. Rarely these patients may present with port-site metastases (PSM) in follow-up. We retrospectively assessed the role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) in them. We aimed to determine the clinical outcome and correlate the survival based on FDG PET/CT findings. MATERIAL AND METHOD: We did a single-center retrospective study in IGBC patients presented with histopathologically proven PSM. FDG PET/CT was done for restaging. The metastatic burden was evaluated. Survival after PSM and overall survival (OS) were assessed in different disease groups. RESULTS: A total of 22 patients (51.86 ± 12.04 years) were included in the study. The mean interval between LC and PSM was 336.7 ± 501.9 days. On FDG PET/CT, isolated single PSM was noted in 21 (95.5%) patients. Apart from PSM, abdominal lymph nodes, GB fossa lesion, and liver metastases were noted in the 10 (45.5%), 6 ( 27.3%), and 7 (31.8%) patients, respectively. FDG PET/CT revealed intra-abdominal disease and visceral metastasis in 11 (50%) and 10 (45.5%) patients. Nineteen (86.4%) patients died in follow-up with a median survival of 328.50 (225.25-804.0) day after PSM. Median OS after LC was 687.00 (362.50-1047.0) days. Patients with PSM plus disease (432.0 days, 255.9-608.1), extra-abdominal metastases (400.0 days, 316.9-483.1), and visceral metastases (400.0 days, 296.2-503.8) had significantly lower OS compared to isolated PSM (1763 days, p = 0.013), the intra-abdominal disease (996.0 days, 753.2-1238.8, p = 0.0340), and non visceral metastasis (807.0 days, 467.5-1146.4, p = 0.037). IGBC presenting as PSM is a distinct clinical entity. FDG PET/CT as functional imaging evaluates the local and metastatic disease burden. There is significantly lower survival in patients with PSM plus disease, extra-abdominal metastases, or visceral metastases. FDG PET/CT was an important prognostic marker in these patients and could help in management.

Relapsed Carcinoma Cervix Presented with Multiple Rare Visceral Metastases: Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Carcinoma cervix spread to locoregional lymph nodes. Distance metastases are uncommon and occur through hematogenous routes in advanced stages. The common sites include bone and lungs. Another organ involvement is uncommon. Computed tomography (CT) and magnetic resonance imaging have a crucial role in diagnosing local and distant metastasis. 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) is a sensitive molecular imaging modality for various cancers, including gynecological ones. We present a case of recurrent cervical carcinoma presented with cervical mass and several rare visceral metastases. 18F-FDG PET/CT is a whole-body modality that accurately localized all lesions in a single study.

Utility of F-18 Fluorodeoxyglucose Positron Emission Tomography - Computed Tomography in Primary Thyroid Lymphoma.

Primary thyroid lymphoma (PTL) is an uncommon malignancy. The majority of PTLs are non-Hodgkin's lymphoma. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) is the state-of-the-art imaging in lymphoma and plays a pivotal role in staging, follow-up, and treatment decisions. There is good evidence that it performs well in a wide variety of nodal and extranodal lymphomas (ENL). However, the data are scarce on its usefulness in rare ENL. Herein, we describe four cases of PTLs and a brief review of the literature. FDG PET/CT was performed at baseline to assess the disease status and response to treatment. This case series highlights the varied appearance of PTL and response to treatment. It establishes the importance of FDG PET/CT in the personalized management of PTL.

Malignant Tracheoparenchymal Fistula in Primary Mediastinal B-Cell lymphoma detected on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Acquired tracheobronchial fistulas are a relatively uncommon complication. Among them, tracheo-mediastinal-parenchymal fistulas are particularly rare. Most of the reported cases are associated with concurrent chemoradiotherapy in lung cancer. It has not been reported in lymphomas. These fistulas are associated with high mortality due to infection and bleeding, and there is no consensus on a definitive optimal therapy. Here, we present a case of tracheoparenchymal fistula in a follow-up primary mediastinal B-cell lymphoma case. This case highlights the utility of fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial diagnosis and follow-up of lymphoma. The PET/CT could show demonstrate the residual disease and differentiate it from other therapy-related benign changes.

F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Case of Subcutaneous T-cell Lymphoma Presenting as Breast Mass and Panniculitis-Like Features: A Rare Entity.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual subtype of cutaneous lymphoma and clinically appears as erythematous, subcutaneous infiltrates, and recurrent papulonodules. It is defined as a rare cytotoxic a/b T-cell lymphoma characterized by primary involvement of subcutaneous tissue-mimicking panniculitis and a predominant CD3+/CD4/CD8+ phenotype in (2005) the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. On metabolic imaging, these lesions are invariably fluorodeoxyglucose (FDG) avid. SPTCL which presents as a breast mass is a rare entity. Here, we present a case of SPTCL presents as FDG avid breast mass and subcutaneous nodules.

Contiguous Multilevel Vertebral Metastasis in Carcinoma Breast Mimicking Spondylodiscitis.

A 59-year old female presented with a lump in the right breast for 6 months. She developed progressively increasing backache for 3 months. Magnetic resonance imaging spine was suggestive of hypointense heterogeneous signal intensity in multiple dorsal vertebrae (D3-D8) and suggestive of Pott's spine. Sonomammography suggested a lesion with irregular margin in the retro-areolar region. Fine-needle aspiration cytology was infiltrating duct carcinoma. Fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography revealed mass in the right breast with axillary lymph node. FDG-avid lytic destructive contiguous lesion was noted in mid-dorsal vertebrae. Apart from it, FDG-avid lytic lesion was also noted in the right iliac bone. The patient underwent vertebral lesion biopsy consistent with metastatic breast carcinoma. This case report demonstrates rare contiguous involvement of multiple vertebrae masquerading Pott's spine.

Establishing the [18F]-FDG Production via Two Different Automated Synthesizers for Routine Clinical Studies: Our Institutional Experiences of 4 years.

INTRODUCTION: [18F]-Fluorodeoxyglucose ([18F]-FDG) is the most widely used positron-emission tomography tracer used for imaging in clinical studies such as early detection of cancer or its malignancies, quantifications, staging, and restaging of several malignancies. For clinical application, routine production of this tracer is mandatory in compliance to regulatory guidelines. Several dedicated commercial synthesizers are currently used for producing[18F]-FDG for clinical usage. Being at hospital radiopharmacy, it is our responsibility and duty to support the clinical service with uninterrupted production and supply of [18F]-FDG. This document describes the production of [18F]-FDG using two different automated synthesizers in terms of its production yield, time of synthesis, and analyze the quality control (QC) of the produced [18F]-FDG. MATERIALS AND METHODS: The precursor, mannose triflate ultra-pure, authentic nonradioactive standard FDG and [18O]-water were obtained from ABX, Germany. Solvents and reagents were purchased from Sigma Aldrich India Ltd. and Fisher Scientific India Ltd., (Mumbai, Maharashtra, India). RESULTS: The protocol developed for the synthesis with MPS-100 synthesizer yield of [18F]-FDG is approximate about 45% End of Bombardment (EOB) with synthesis time of around 35 min, whereas with F300E synthesizer it is around 60% with synthesis time of 25 min. The quality of the tracer produced by both synthesizers is at par with the QC parameter for clinical applications. CONCLUSIONS: Finally, we have developed the production using two automated synthesis modules which have the capability to produce [18F]-FDG, to do the patient studies in good yield and purity. Our protocol is simple, reproducible, and robust.

Do Current Radiation Safety Guidelines allow the Safe Release of a Thyroid Cancer Patient after High-dose Radioiodine Therapy? An Indian Perspective.

AIM: Radionuclide therapy may produce a significant radiation exposure risk to the patient's caregivers. The study aims to assess the radiation exposure rate to caregivers after the patient's discharge from the isolation ward. MATERIALS AND METHODS: Patients of the well-Differentiated thyroid cancer (DTC)were given high-dose radioiodine therapy as an inpatient. Their radiation exposure was measured daily, and they were discharged once the exposure rate falls as per standard guidelines. Detail counseling of the patient and caregiver about radiation safety was done before admission and at the time of discharge. Caregivers were given thermoluminescence dosimeter (TLD) to wear as a locket for 7 days. Radiation exposure received by the caregiver was measure after that. RESULTS: A total of 22 patients (8 male and 14 female) of DTC were recruited in the study. The mean age was 39.0 ± 14.5 years. Patients were treated with 3.79 ± 1.07 (102.4 ± 28.9 mCi) (1.85-5.55 (50-150 mCi) GBq of radioiodine. They were discharged from the isolation ward at a radiation level of 0.028 ± 0.015 mSv/h (3.193 ± 1.71 mR). The mean effective dose received by the caregiver was 14.60 ± 3.43 mSv (1460 ± 343 mR) (9.73-24.25 (973-2765 mR) mSv. CONCLUSION: Our study denotes that the caregivers of DTC patients receive a significant radiation dose. It was well above the caregiver's annual dose-limit constraints regarding the rationales well as international guidelines of 5 mSv/yr. These could be related to the long travel in public transport and housing conditions. There is a need for patient-specific discharge criteria rather than following standard guidelines to minimize radiation exposure to caregivers.

Incidental Diagnosis of Multiple Paragangliomas by Ga-68 DOTANOC Positron Emission Tomography-Computed Tomography.

A 65-year-old man presented with intermittent abdominal pain for three months. Abdominal ultrasonography revealed a mass in the body of the pancreas. Moreover, abdominal contrast-enhancing computed tomography revealed a homogenously enhancing mass in the body of the pancreas. Scan findings were in favor of the neuroendocrine tumor, and the serum chromogranin level was slightly raised (111.9 ng/ml, normal <98). He had no history of vomiting, jaundice, melena, hematemesis, constipation, diarrhea, weight gain, weight loss, loss of appetite, and fever. He also had no symptoms related to the excessive production of catecholamines, such as hypertension. The patient was referred for Ga-68 DOTANOC positron emission tomography-computed tomography (Ga-68 DOTANOC PET-CT) for further evaluation. The scan was done to rule out metastatic disease or other synchronous lesions to plan surgical excision. The Ga-68 DOTANOC PET-CT revealed a pancreatic lesion with no other abdominal lesions. We noted multiple tracer avid soft tissue lesions on both sides of the neck that were not diagnosed previously. This case report demonstrates a rare case with multiple paragangliomas diagnosed by the Ga-68 DOTANOC PET-CT. This finding could lead to changes in patient management.