Internal dosimetry and biodistribution of indigenously prepared 177Lu-DOTA-rituximab in lymphoma and other hematological malignancies treated with rituximab.

OBJECTIVE: The aim of this study was to evaluate the biodistribution and dosimetry of lutetium-177-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (177Lu-DOTA)-rituximab in CD20+ non-Hodgkin's lymphoma and other hematological malignancies treated with rituximab. METHODS: The standard dosimetry protocol was used, with cold rituximab infusion, then a diagnostic activity of 177Lu-DOTA-rituximab. Planar images were acquired at multiple time points. Normal organs and tumor dosimetry were performed by using organ and tumor-specific regions of interest and whole-body counts were obtained serially after pixel matched, background, scatter, and attenuation correction. The mean radiation absorbed doses were obtained from OLINDA/EXM v2.1.1 and ORIGIN software. RESULTS: A total of 22 patients were included in this study. Prolonged blood pool clearance of 177Lu-DOTA-rituximab with long residence time in the blood pool and normal organs were observed. The whole body effective half-life was 104.5 ±â€…22 h. The mean total body radiation absorbed dose was 0.208 ±â€…0.03 mGy/MBq and the mean total body effective dose was 0.196 ±â€…0.05 mGy/MBq of 177Lu-DOTA-rituximab. The mean radiation absorbed doses of 0.613 ±â€…0.21, 1.68 ±â€…2, 1.01 ±â€…0.42, and 0.136 ±â€…0.02mGy/MBq were seen for the liver, spleen, kidneys, and bone marrow, respectively. Tumor lesion uptake was noticed in two patients with tumor radiation absorbed doses were 0.842 mGy/MBq in one and 9.9 mGy/MBq in the other patient. A strong correlation was obtained between the cumulative activities of radiation-absorbed doses derived from ORIGIN and OLINDA software methods at a significant P value less than 0.001. CONCLUSION: The results of our study demonstrated favorable biodistribution and dosimetry of indigenously produced 177Lu-DOTA-rituximab in patients with CD20+ lymphoma. These results can be used for future studies of radioimmunotherapy employing 177Lu-DOTA-rituximab.

Role of Novel Quantitative Imaging Techniques in Hematological Malignancies.

Hematological malignancies exhibit a widespread distribution, necessitating evaluation of disease activity over the entire body. In clinical practice, visual analysis and semiquantitative parameters are used to assess 18F-FDGPET/CT imaging, which solely represents measurements of disease activity from limited area and may not adequately reflect global disease assessment. An efficient method for assessing the global disease burden of hematological malignancies is to employ PET/computed tomography based novel quantitative parameters. In this article, we explored novel quantitative parameters on PET/CT imaging for assessing global disease burden and the potential role of artificial intelligence (AI) to determine these parameters in evaluation of hematological malignancies.

Multifocal Burkholderia cepacia Infection in Postrenal Transplantation Fever : Role of 18 F-FDG PET/CT in Treatment Optimization.

ABSTRACT: Nosocomial Burkholderia cepacia infection in the clinical setting of postrenal transplantation pyrexia of unknown origin and the role of 18 F-FDG PET/CT in treatment optimization in such situation is presented in this report. The consequence of fastidious infection by nosocomial colonizing organisms like B. cepacia can be catastrophic in immunocompromised postrenal transplant individuals causing severe urinary tract infection. In the presented case, following 2 weeks of IV antibiotics, the patient didn't show clinical response, and FDG PET scan recognized multifocal infective sites early, likely representing immune reconstitution inflammatory syndrome and timely appropriate and optimal treatment salvaged the renal graft.

Evaluation of Ectopic Kidney Located at the Deep Subcutaneous Region of the Abdominal Wall: Role of Diuretic Renography with 99mTc-DTPA.

An ectopic kidney is often found inadvertently during CT, ultrasonography, MRI, or urologic physical examination. Ectopic kidneys usually occur in the pelvis. A pelvic ectopic kidney may be misinterpreted for a pelvic tumor by less experienced physicians and surgeons. We present an extremely rare case of ectopic kidney in the deep subcutaneous region of the abdominal wall and associated with the additional abnormality of spina bifida. MRI found an ectopic kidney but failed to identify ureteropelvic drainage. Diuretic renography with 99mTc-diethylenetriaminepentaacetic acid showed normal functioning and identified nonobstructive ureteropelvic drainage of the ectopic subcutaneous kidney.

Assessing Krenning's score on 68Ga-DOTATATE PET-CT and miPSMA score on 68Ga-PSMA-11 PET-CT in TENIS: a comparison with FDG PET/CT and examining the feasibility of targeted radionuclide therapy.

OBJECTIVES: The objective of this study was to assess receptor expression in metastatic differentiated thyroid carcinoma patients with progressive elevated thyroglobulin and negative iodine scintigraphy, we used 68Ga-DOTATATE [Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)] (Krenning's score) and 68Ga-PSMA-11 (Gallium-68 prostate-specific membrane antigen-11) PET-computed tomography (CT) [molecular imaging prostate-specific membrane antigen (miPSMA) score]. Patients with Krenning's score 3 and above and miPSMA score 2 and above were considered to determine the incidence of patients, who would qualify for treatment with 177Lu-DOTATATE/PSMA [Lutetium-177 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)/prostate-specific membrane antigen]-based therapy. In addition, we compared 68Ga-DOTATATE and 68Ga-PSMA-11 PET-CT with 2-deoxy-2-[F-18]fluoroglucose (18F-FDG) PET-CT (using maximum standardized uptake value). MATERIALS AND METHODS: A total of 74 patients with histopathologically proven metastatic differentiated thyroid carcinoma with thyroglobulin elevation and negative iodine scintigraphy syndrome were studied retrospectively. They all had 18F-FDG, 68Ga-DOTATATE, and 68Ga-PSMA-11 PET-CT scans available for undertaking this analysis. The lesions detected by 68Ga-DOTATATE and 68Ga-PSMA-11 were evaluated using Krenning's and miPSMA scores. In addition, quantitative comparisons of maximum standardized uptake values for 68Ga-DOTATATE and 68Ga-PSMA-11, as well as with 18F-FDG, were conducted. RESULTS: Patient-wise analysis revealed positivity rates of 40.5% for 68Ga-DOTATATE, 41.89% for 68Ga-PSMA-11, and 75.67% for 18F-FDG. Among the 74 patients, 14 (18.91%) were deemed eligible for 177Lu-DOTATATE/PSMA-617 therapy based on Krenning's score of 3 and above both/either miPSMA score of 2 and above on 68Ga-DOTATATE or 68Ga-PSMA-11 PET-CT. Within this subgroup, seven out of 74 patients (9.45%) were eligible for 177Lu-DOTATATE therapy, and nine out of 74 patients (12.16%) were eligible for 177Lu-PSMA-targeted therapy. Four patients were eligible for both therapies. CONCLUSION: Among thyroglobulin elevation and negative iodine scintigraphy patient's subgroup, 9.45% could qualify for 177Lu-DOTATATE and 12.16% for 177Lu-PSMA-617. Four were eligible for both therapies. Given the lack of effective therapies, this subset of patients warrants consideration for radionuclide therapy exploration.

Factors Predicting Prognosis in Metastatic Grade 1 Gastro-entero-pancreatic Neuroendocrine Tumors.

INTRODUCTION: The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) has steadily increased. These tumors are considered relatively indolent even when metastatic. What determines survival outcomes in such situations is understudied. MATERIALS AND METHODS: Retrospective analysis of a prospectively maintained NET clinic database, to include patients of metastatic grade 1 GEP-NET, from January 2018 to December 2021, to assess factors affecting progression-free survival (PFS). RESULTS: Of the 589 patients of GEP-NET treated during the study period, 100 were grade 1, with radiological evidence of distant metastasis. The median age was 50 years, with 67% being men. Of these, 15 patients were observed, while 85 patients received treatment in the form of surgery (n = 32), peptide receptor radionuclide therapy (n = 50), octreotide LAR (n = 22), and/or chemotherapy (n = 4), either as a single modality or multi-modality treatment. The median (PFS) was 54.5 months. The estimated 3-year PFS and 3-year overall survival rates were 72.3% (SE 0.048) and 93.4% (SE 0.026), respectively. On Cox regression, a high liver tumor burden was the only independent predictor of PFS (OR 3.443, p = 0.014). The 5-year OS of patients with concomitant extra-hepatic disease was significantly lower than that of patients with liver-limited disease (70.7% vs. 100%, p = 0.017). CONCLUSION: A higher burden of liver disease is associated with shorter PFS in patients with metastatic grade I GEP-NETs. The OS is significantly lower in patients with associated extrahepatic involvement. These parameters may justify a more aggressive treatment approach in metastatic grade 1 GEP-NETs.

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-ß and SPL Pathways in the Human Cornea.

Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-ß) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-ß and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-ß1 (ß1), 1 µM sphingosine-1-phosphate (S1P), and 5 µM Sphingosine kinase inhibitor 2 (I2). Five groups were tested: (1) control (no treatment); rescue groups; (2) ß1/S1P; (3) ß1/I2; prevention groups; (4) S1P/ß1; and (5) I2/ß1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-ß signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-ß binding proteins (LTBPs), TGF-ß receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I2 prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I2 prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I2 treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-ß receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I2 as a novel therapy for corneal fibrosis.

Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of 131 I-Whole-Body Scintigraphy with Regional SPECT/CT.

Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to 60% of patients. The presence of distant metastasis impacts overall survival and prognosis. The lungs, bones, and the brain are typically involved in distant sites with less common metastatic sites that include the liver, kidney, skeletal muscle, adrenal glands, bladder, and skin. These unusual sites are rare and pose a diagnostic challenge and impact clinical decision-making to a great extent. The radioiodine 131 I whole-body scintigraphy with single-photon emission computed tomography/computed tomography can provide a thorough investigation of unusual sites of uptake leading to diagnosis of these metastases. We present a case series of DTC showing unusual sites of metastasis and/or radioiodine uptake in urinary bladder, in the third metacarpal bone of left hand and lastly in the forearm at postoperative hypertrophic scar area.

Incidental Detection of Second Primary Thyroid Malignancy in Patients of Metastatic Castration-Resistant Prostate Carcinoma: Documentation on 68 Ga-PSMA-11 and 64 CuCl 2 PET/CT.

ABSTRACT: Second primary tumors are being increasingly detected owing to and in proportion to the use of advanced imaging modalities including PET/CT. Patients suffering from prostate cancer have been reported to have increased second primary cancers of gastrointestinal tract, urinary bladder, and thyroid. We herein describe incidental detection of thyroid carcinoma, in 2 patients of mCRPC (metastatic castration-resistant prostate carcinoma) undergoing preradioligand therapy workup, on 68 Ga-prostate-specific membrane antigen PET/CT initially, subsequently also observed on multitracer PET/CT ( 64 CuCl 2 and 18 F-FDG). Thus, the potential of PET/CT for early in vivo second primary detection in mCRPC setting is illustrated in the aforementioned 2 patients.

Triple Tumors (Neuroendocrine Tumor, Schwannoma, and Papillary Thyroid Carcinoma) With Brain Lesions in a Single Patient Demonstrating Avidity on 68 Ga-DOTATATE PET/CT and Their Characterization With FDG-PET/CT and Brain MRI.

ABSTRACT: Neuroendocrine tumor (NET) typically spreads to the liver, lymph nodes, lungs, and skeleton. Brain metastasis in NET is uncommon. Therefore, each case of detected brain metastases in NET is crucial for the development of treatment guidelines for these types of tumors. We present a unique case of triple tumors (NET, papillary thyroid carcinoma, and schwannoma) in a single patient who presented with neurological symptoms and somatostatin receptor-avid T2 hyperintense multiple metastatic brain lesions from NET on 68 Ga-DOTATATE-PET/CT scan and brain MRI. Despite the rarity of brain metastases in NET, we conclude that the presence of neurological sign or symptoms and/or the detection of somatostatin receptor-avid brain lesions in patients with NET should raise suspicion of brain metastases.

Comprehensive Review of the Imaging Recommendations for Diagnosis, Staging, and Management of Thyroid Carcinoma.

Thyroid cancer is the most common head and neck cancer (HNC) in the world. In this article, we comprehensively cover baseline, posttreatment, and follow-up imaging recommendations for thyroid carcinomas along with the eighth edition of the tumor, node, metastasis (TNM) staging system proposed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). We include characterization and risk stratification of thyroid nodules on ultrasound (US) proposed by various international bodies. Management guidelines (depending upon the type of thyroid carcinoma) based on the international consensus recommendations (mainly by the American Thyroid Association) are also extensively covered in this article, including the role of a radioiodine scan. The management of recurrent disease is also briefly elucidated in this article. In addition, we cover the risk factors and etiopathogenesis of thyroid carcinoma along with the non-imaging diagnostic workup essential for thyroid carcinoma management, including the significance of genetic mutations. US is the diagnostic imaging modality of choice, with US-guided fine needle aspiration (FNA) being the procedure of choice for tissue diagnosis. The roles of computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) in thyroid carcinoma staging are also specified. Through this article, we aim to provide a comprehensive reference guide for the radiologists and the clinicians in the pursuit of optimal care for patients with thyroid carcinoma.

18 F-Fluorodeoxyglucose Uptake in Bilateral Diaphragmatic Crura: A Relatively Uncommon Benign Variant Noted in a Treated Case of Extraosseous Paraspinal Ewing's Sarcoma.

A toddler was diagnosed with extraosseous Ewing's sarcoma, primary large epidural paraspinal soft tissue in the lumbar region encasing the cord and neural foramen from D12-L1 to L4-L5. After eight cycles of induction chemotherapy with vincristine, doxorubicin, and cyclophosphamide alternating with etoposide and ifosfamide, 18 F-FDG positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) scan confirmed no active disease. Later external beam radiotherapy (EBRT) at D10-L5 was completed. At 3 months follow-up, 18 F-FDG-PET/CT reconfirmed no residual/active disease; however, a new incidental finding of diffuse benign bilateral diaphragmatic 18 F-FDG uptake was noted in the clinically asymptomatic patient, which remained unexplained.

Concomitant Bilateral Inferior Gluteal Lymph Node Involvement in Metastatic Prostate Adenocarcinoma Detected on 68 Gallium-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

An unusual and unique case of prostate adenocarcinoma with involvement of bilateral inferior gluteal lymph nodes is reported. The patient was a 42-year-old male, with conventional prostatic adenocarcinoma (Gleason score: 5 + 4 = 9), who, during disease progression with rising serum prostate specific antigen levels following medical androgen deprivation therapy, demonstrated new prostate-specific membrane antigen expressing metastatic intermuscular deposits in the bilateral gluteal region, subsequently proven to be bilateral inferior gluteal nodal metastasis. A therapeutic implication to this may be that these nodes usually fall beyond the range covered by the therapeutic radiation field coverage where external radiotherapy is the advocated modality of choice and are not easily reachable through standard surgical procedures. As a result, they could have an impact on the way patients are clinically treated and on their prognosis.

Unusual Metastatic Sites of Testis and Rectum in Prostate Cancer Detected by 68 Ga-PSMA-11 PET/CT Imaging at Initial Staging.

Imaging plays a pivotal role in defining the extent of disease and deciding therapeutic strategies in recently diagnosed high-risk prostate cancer. Standard-of-care conventional imaging may often miss rare metastatic disease sites. We herein present a unique case of prostate cancer where 68 Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) detected two unusual metastatic sites (testis and rectum) in a single patient at initial staging, resulting in an accurate determination of the extent of disease, more tailored multimodal treatment planning, and exploration of the theragnostic potential.

Cutaneous, Subcutaneous, and Bilateral Adrenal Gland Metastases in Progressive Prostate Carcinoma: Theranostic Potential of 68 Ga-PSMA-11 PET/CT Imaging and 177 Lu-PSMA-617 Therapy.

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.

Prospective evaluation of 68 Ga-NODAGA-RGD PET-CT in patients of carcinoma thyroid with thyroglobulin elevated negative radioiodine scintigraphy (TENIS) with a head-to-head comparison with FDG-PET/CT.

BACKGROUND AND AIM: This study aimed to examine the expression of RGD binding integrins in patients of elevated serum thyroglobulin (Tg) level with negative radioiodine scintigraphy (TENIS) employing 68 Ga-NODAGA-RGD PET-CT. MATERIAL AND METHODS: This was a prospective study involving 30 proven cases of TENIS with histopathological diagnosis of differentiated thyroid carcinoma post-surgery. In addition to observing the lesional concentration on 68 Ga-NODAGA-RGD PET-CT, a 4-point visual grading system (grade I-IV), was undertaken to estimate the degree of radiotracer avidity, for potential of theranostics. RESULTS: On 18 F-FDG-PET/CT, the uptake was seen in 182 lesions out of a total of 200 (91%). 68 Ga-NODAGA-RGD PET-CT showed expression in a total of 110/200 (55%) lesions. On patient-specific analysis, 68 Ga-NODAGA-RGD PET-CT was positive for the disease in 21/30 patients (70%) and negative in 9/30 (30%) patients. The overall patient-specific sensitivity and specificity of 68 Ga-NODAGA-RGDPET-CT were 75% and 100%, respectively. 18 F-FDG PET-CT was positive for the disease in 26/30 patients (86.66%) and negative in 4/30 (13.33%) patients. The overall patient-specific sensitivity and specificity of 18 F-FDG-PET/CT were 92.86% and 100%, respectively. The 4-point visual grading system revealed 14/200 (7%) lesions demonstrating Grade I uptake, 49/200 (24.5%) lesions grade II uptake, 17/200 (8.5%) lesions grade III uptake and 40/200 (20%) lesions grade IV uptake. CONCLUSION: The results suggested that RGD-binding integrin is expressed in a sizeable fraction of metastatic lesions of TENIS cases, albeit demonstrating a varying degree of uptake. Out of the soft tissue, lung, and bone lesions, metastatic bone lesions showed more RGD affinity than other sites. The patients with substantial RGD uptake on a 4-point visual grading system may be potential targets for RGD-based therapy.

Sphingolipid biosynthetic inhibitor L-Cycloserine prevents oxidative-stress-mediated death in an in vitro model of photoreceptor-derived 661W cells.

Oxidative stress plays a pivotal role in the pathogenesis of several neurodegenerative diseases. Retinal degeneration causes irreversible death of photoreceptor cells, ultimately leading to vision loss. Under oxidative stress, the synthesis of bioactive sphingolipid ceramide increases, triggering apoptosis in photoreceptor cells and leading to their death. This study investigates the effect of L-Cycloserine, a small molecule inhibitor of ceramide biosynthesis, on sphingolipid metabolism and the protection of photoreceptor-derived 661W cells from oxidative stress. The results demonstrate that treatment with L-Cycloserine, an inhibitor of Serine palmitoyl transferase (SPT), markedly decreases bioactive ceramide and associated sphingolipids in 661W cells. A nontoxic dose of L-Cycloserine can provide substantial protection of 661W cells against H2O2-induced oxidative stress by reversing the increase in ceramide level observed under oxidative stress conditions. Analysis of various antioxidant, apoptotic and sphingolipid pathway genes and proteins also confirms the ability of L-Cycloserine to modulate these pathways. Our findings elucidate the generation of sphingolipid mediators of cell death in retinal cells under oxidative stress and the potential of L-Cycloserine as a therapeutic candidate for targeting ceramide-induced degenerative diseases by inhibiting SPT. The promising therapeutic prospect identified in our findings lays the groundwork for further validation in in-vivo and preclinical models of retinal degeneration.

Clinical Internal Dosimetry and Biodistribution of 177 Lu-DOTA-Trastuzumab in HER2-Positive Metastatic and Locally Advanced Breast Carcinoma.

OBJECTIVE: The aim of this study was to assess the biodistribution and dosimetry of 177 Lu-DOTA-trastuzumab in patients with HER2-positive breast carcinoma using whole-body (WB) planar imaging at multiple time points. PATIENTS AND METHODS: This study was a prospective evaluation of HER2-positive metastatic/locally advanced breast carcinoma patients who underwent gamma camera imaging for dosimetry and biodistribution studies by using 177 Lu-DOTA-trastuzumab. The standard diagnostic dosimetry protocol was followed, which included cold trastuzumab injection followed by in-house produced 177 Lu-DOTA-trastuzumab. Serial WB planar images (anterior and posterior) were obtained on gamma camera after the infusion of 177 Lu-DOTA-trastuzumab at multiple time points. Whole-body and organ regions of interest were drawn, and the numbers of disintegrations were obtained. The mean absorbed doses for the liver, spleen, kidneys, heart, red marrow, and tumor were obtained from OLINDA EXM v2.1.1 and ORIGIN software. RESULTS: The study included a cohort of 21 female breast carcinoma patients. Tracer activity ( 177 Lu-DOTA-trastuzumab) was noted in the physiological organs such as the liver, spleen, kidneys, heart, as well as in the tumors. On visual analysis of 177 Lu-DOTA-trastuzumab biodistribution, the liver activity showed gradual clearance over time, and although spleen was comparatively faintly visualized than liver and similarly, kidneys were faintly visualized suggestive of the alternate route of tracer excretion. The maximum number of patients (n = 12) showed 2 components of clearance, namely, fast and slow. The average effective half-life of all the patients (including single and 2 components of clearance) was 106.25 ± 22.14 hours (84.11-128.39 hours). The mean absorbed dose for the liver, spleen, kidneys, heart, whole body, and red marrow was 1.0702 ± 0.731, 1.4114 ± 0.462, 1.4232 ± 0.364, 1.4719 ± 0.602, 0.2412 ± 0.0295, and 0.1485 ± 0.0213 mGy/MBq, respectively, by OLINDA EXM and 0.5741 ± 0.333, 0.8096 ± 0.224, 0.7943 ± 0.235, 1.8971 ± 0.713, and 0.09619 ± 0.0144 for liver, spleen, kidneys, heart and whole body respectively by ORIGIN. The absorbed radiation dose for tumor was 1.94E+2 by OLINDA EXM software and 1.78E+2 by ORIGIN software. In this study, during and after infusion of 177 Lu-DOTA-trastuzumab, no major adverse effects were noted in any patient except 1 patient who had grade 1 nausea and managed conservatively by antiemetic drug. CONCLUSIONS: The results of our study demonstrated expected and favorable biodistribution and dosimetry with 177 Lu-DOTA-trastuzumab in HER2-positive breast carcinoma patients. We noticed the mean absorbed dose to the normal organs within the limits of maximum tolerable dose, and also tumor dose was higher than the normal liver dose. Therefore, we conclude that 177 Lu-DOTA-trastuzumab radioimmunotherapy is feasible and a safe treatment option for treating HER2-positive breast carcinoma patients.

Evaluation of prostate-specific membrane antigen expression in locally advanced or metastatic breast carcinoma with 68 Ga-PSMA-11 positron-emission tomography/computed tomography imaging for potential theranostics.

BACKGROUND AND AIM: Prostate-specific membrane antigen (PSMA) is ubiquitously expressed in tumor-associated neovasculature and may be a potential theranostic in many solid cancers, including breast carcinoma (BC). Herein, we analyzed the presence of PSMA in BC, through qualitative and quantitative parameters on 68 Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT), across various hormonal subtypes. METHODS: This study examined 41 female patients of BC. All underwent 68 Ga-PSMA-11 PET/CT. For qualitative analysis, a visual estimation of PSMA expression was performed as per miPSMA scoring system (VISION trial) and a score ≥2 was considered eligible for lutetium-177 ( 177 Lu)-PSMA-617 radioligand therapy (Lu-PRLT). For quantitative analysis, maximum standardized uptake values (SUVmax) were determined and ratios >1 for SUVmax lesion to SUVmax liver were considered eligible for Lu-PRLT. PSMA expression was correlated with hormonal status using Chi-square test. The sensitivity, specificity and area under curve (AUC) of PSMA expression were determined using receiver-operating characteristics analysis ( P < 0.05). RESULTS: A total of 19 patients (46.3%) and 15 patients (36.7%) in stage IV were found eligible for Lu-PRLT based on qualitative and quantitative analyses, respectively. Strong PSMA expression was detected in triple-negative and hormonal receptors-negative/human epidermal growth factor receptor 2-positive status on qualitative PSMA expression analysis. A sensitivity of 65.5%, specificity of 93.3% and AUC of 0.857 for SUVmax 6.5 on 68 Ga-PSMA-11 PET/CT were detected for PSMA expression for considering Lu-PRLT. CONCLUSION: We found a modest number of BC patients suited for Lu-PRLT, indicating that PSMA PET/CT imaging may be a valuable modality for selecting theranostics in a carefully selected group of breast carcinoma.

Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling.

Vesicating chemicals like sulfur mustard (SM) or nitrogen mustard (NM) can cause devastating damage to the eyes, skin, and lungs. Eyes, being the most sensitive, have complicated pathologies that can manifest immediately after exposure (acute) and last for years (chronic). No FDA-approved drug is available to be used as medical counter measures (MCMs) against such injuries. Understanding the pathological mechanisms in acute and chronic response of the eye is essential for developing effective MCMs. Here, we report the clinical and histopathological characterization of a mouse model of NM-induced ocular surface injury (entire surface) developed by treating the eye with 2% (w/v) NM solution for 5 min. Unlike the existing models of specific injury, our model showed severe ocular inflammation, including the eyelids, structural deformity of the corneal epithelium and stroma, and diminished visual and retinal functions. We also observed alterations of the inflammatory markers and their expression at different phases of the injury, along with an activation of acidic sphingomyelinase (aSMase), causing an increase in bioactive sphingolipid ceramide and a reduction in sphingomyelin levels. This novel ocular surface mouse model recapitulated the injuries reported in human, rabbit, and murine SM or NM injury models. NM exposure of the entire ocular surface in mice, which is similar to accidental or deliberate exposure in humans, showed severe ocular inflammation and caused irreversible alterations to the corneal structure and significant vision loss. It also showed an intricate interplay between inflammatory markers over the injury period and alteration in sphingolipid homeostasis in the early acute phase.