Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative review.

As new molecular tracers are identified to target specific receptors, tissue, and tumor types, opportunities arise for the development of both diagnostic tracers and their therapeutic counterparts, termed "theranostics." While diagnostic tracers utilize positron emitters or gamma-emitting radionuclides, their theranostic counterparts are typically bound to beta and alpha emitters, which can deliver specific and localized radiation to targets with minimal collateral damage to uninvolved surrounding structures. This is an exciting time in molecular imaging and therapy and a step towards personalized and precise medicine in which patients who were either without treatment options or not candidates for other therapies now have expanded options, with tangible data showing improved outcomes. This manuscript explores the current state of theranostics, providing background, treatment specifics, and toxicities, and discusses future potential trends.

Comparison of 68Ga-DOTA-NaI3-Octreotide/tyr3-octreotate positron emission tomography/computed tomography and contrast-enhanced computed tomography in localization of tumors in multiple endocrine neoplasia 1 syndrome.

The optimum imaging modality for the screening of multiple endocrine neoplasia type 1 (MEN1)-associated tumors is not well established. Here, we compare the performance of contrast-enhanced CT (CECT) versus 68Ga DOTA-NOC/TATE PET/CT in MEN1 patients. The retrospective case record study is conducted at a tertiary health-care center. Thirty-four patients, who have undergone both CECT and 68Ga DOTA-NOC/ TATE PET, were included in the analysis. CECT had higher per-lesion sensitivity than 68Ga DOTA-NOC/TATE PET/CT for the detection of parathyroid lesions, (82.6% vs. 24.6%, P < 0.001). 68Ga DOTA-NOC/TATE PET/CT had higher per-lesion sensitivity than CECT for the detection of metastases (85% vs. 47.5%, P < 0.001) and gastrinomas (90% vs. 10%, P = 0.003). When combined use of the two imaging modalities is compared to CECT alone (63.7% vs. 93.1%, P = 0.00012) and 68Ga-DOTA-NOC/TATE PET/CT alone (74.1% vs. 93.1%, P = 0.0057), it provided significantly higher per-lesion sensitivity for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 68Ga-DOTA-NOC/ TATE PET was more sensitive for the detection of gastrinomas and metastases than CECT, whereas it was less sensitive for the detection of parathyroid lesions than CECT. The combined use of both the imaging modalities significantly increases the sensitivity for detection of GEP-NETs.

Exendin-4-based imaging in endogenous hyperinsulinemic hypoglycaemia cohort: A tertiary Endocrine centre experience.

CONTEXT: Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results. OBJECTIVE: To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities. DESIGN: Retrospective cross-sectional study. PATIENTS: We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n = 11), Munchausen syndrome (MS) (n = 2) and inconclusive (n = 1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma. MAIN OUTCOME MEASURES: True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization. RESULTS: In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS. CONCLUSION: 68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.

Diffuse Large B-Cell Lymphoma in the Era of Precision Oncology: How Imaging Is Helpful.

Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's lymphoma. As treatments continues to evolve, so do imaging strategies, and positron emission tomography (PET) has emerged as the most important imaging tool to guide oncologists in the diagnosis, staging, response assessment, relapse/recurrence detection,and therapeutic decision making of DLBCL. Other imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and conventional radiography are also used in the evaluation of lymphoma. MRI is useful for nervous system and musculoskeletal system involvement and is emerging as a radiation free alternative to PET/CT. This article provides a comprehensive review of both the functional and morphological imaging modalities, available in the management of DLBCL.

Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients.

OBJECTIVE: PSMA-617 is reported to exhibit very high binding affinity towards PSMA receptors, over-expressed on prostate cancer cells and therefore, (177)Lu-labeled PSMA-617 is expected to play a pivotal role in the clinical management of patients suffering from ca prostate. The objective of the present study is to formulate the patient dose of (177)Lu-labeled PSMA-617, pre-clinical studies in animal model and clinical investigation in limited number of prostate cancer patients as well evaluating its potential for theranostic application. EXPERIMENTAL: Patient dose of 7.4 GBq (200 mCi) of (177)Lu-labeled PSMA-617 was prepared by incubating 100 µg of PSMA-617 with (177)LuCl3 at 95 °C for 15 minutes. Radiochemical purity as well as in-vitro stability of the preparation was determined by PC and HPLC methods. The pharmacokinetic behavior and in-vivo distribution of the agent were studied by carrying out biodistribution studies in normal male Wistar rats. Preliminary clinical investigation was performed in 7 patients suffering from prostate cancer. RESULTS: The complex was prepared with >98% radiochemical purity under the optimized reaction protocols and the preparation exhibited adequate in-vitro stability. Biodistribution studies revealed no significant uptake in any of the major organ/tissue along with major clearance through renal pathway. Clinical studies showed similar distribution in lesions and physiologic areas of uptake as seen in diagnostic (68)Ga-PSMA-11 PET scans performed earlier. CONCLUSION: Preliminary clinical studies indicated the promising potential of the agent for theranostic applications. However, further investigations in large pool of patients are warranted to establish the theranostic potential of the agent.

Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome.

BACKGROUND: Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of (68)Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. MATERIALS AND METHODS: Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and (68)Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and (68)Ga-DOTANOC PET/CT was compared. RESULTS: Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). (68)Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). CONCLUSION: CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. (68)Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions.

Vitamin D as a marker of cognitive decline in elderly Indian population.

OBJECTIVES: Very few studies in India have addressed the role of vitamin D in cognitive function. The present study was conducted to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive impairment and homocysteine levels in the elderly Indian population. MATERIALS AND METHODS: The study population consisted of patients with dementia (Group A, n = 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total homocysteine were done. RESULTS: Significant decreased concentration of 25(OH)D and increased concentration of homocysteine was observed. Association of serum levels of vitamin D with markers of cognitive decline as well as serum homocysteine levels was observed in patients with dementia and MCI when compared to controls. CONCLUSION: Correlation of vitamin D with markers of cognitive decline and homocysteine opens a new door for early diagnosis of cognitive impairment.

Mortui vivos docent--the dead teach the living: 18-flurodeoxyglocose positron emission tomography-computed tomography findings in a case of intravascular B cell lymphoma.

Intravascular large B-cell lymphoma is a rare and aggressive variant of diffuse large B-cell non-Hodgkin's lymphoma. Its atypical presentation often delays the diagnosis and due to its aggressive behavior, the diagnosis is made post-mortem in half of the cases. We present FDG PET/CT findings in a case of IVLCL. In our case, the report of the patient's bone marrow biopsy after death of the patient revealed the presence of IVLCL. After availability of final diagnosis, we reviewed the literature and a better explanation of the FDG PET/CT findings could be obtained. We describe this case, to call for heightened awareness in physicians for the rare but possible diagnosis of IVCLL, particularly in an elderly patient who presents with fever of unknown origin and demonstrates similar FDG PET/CT findings. Considering the characteristic scan findings described in our patient and other cases in literature, FDG PET/CT can be used in suspected cases of IVLCL for early diagnosis of this rapidly fatal malignancy.

Malignant amelanotic melanoma--a diagnostic surprise: Flurodeoxyglocose Positron Emission Tomography-Computed Tomography and immunohistochemistry clinch the 'final diagnosis'.

Amelanotic melanoma is a rare malignancy and the prognosis is usually poorer than that of pigmented melanomas, because of delay in establishing the correct diagnosis, and in treatment initiation. In our case report, we present a the Flurodeoxyglocose Positron Emission Tomography-Computed Tomography (FDG PET/CT) findings of a patient suffering from malignant amelanotic melanoma and its histopathological confirmation and immunohistochemistry (IHC) correlation In the described case, amelanotic melanoma masqueraded as adenocarcinoma of the rectum in the pathology as well the clinical course. Our case highlights the importance of obtaining a tissue diagnosis and IHC confirmation whenever unusual PET/CT findings are encountered.

F-18 flourodeoxyglucose positron emission tomography/computed tomography findings in a case of hepatosplenic T-cell lymphoma.

T-cell lymphoma (TCL) is a biologically diverse and uncommon group of lymphoid malignant diseases. Compared with its B-cell counterparts, TCL is notably more difficult to diagnose and manage owing to its rarity and biologic heterogeneity. Hepatosplenic TCL is an extremely rare subtype of TCL. A 37-year-old Indian male presented to his physician with swelling and pain in left hypochondrium. Clinical examination revealed pallor, icterus and massive splenomegaly. His blood examination revealed pancytopenia. His bone marrow biopsy was suggestive of lymphoma. Whole body F-18 flourodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan revealed diffuse increased metabolic activity in massively enlarged spleen, liver and bone marrow. There was no evidence of metabolically active lymphadenopathy anywhere in the body. Guided by the FDG PET/CT findings, a liver biopsy was advised. Liver histopathology revealed the presence of hepatosplenic TCL. A final diagnosis of hepatosplenic TCL with liver, spleen and bone marrow involvement was made. Even though rare, hepatosplenic TCL should be considered as a possible diagnosis in patients presenting with similar clinical picture and FDG PET/CT scan findings.