Cutaneous, Subcutaneous, and Bilateral Adrenal Gland Metastases in Progressive Prostate Carcinoma: Theranostic Potential of 68Ga-PSMA-11 PET/CT Imaging and 177Lu-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 68Ga-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 177Lu-PSMA-617 treatment for these extremely rare metastatic sites.

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.

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.

Normal physiological distribution and tumor localization of 64 CuCl 2 in different human malignancies along with semiquantitative scoring: a comparative evaluation with 18 Fluorodeoxyglucose ( 18 FDG) PET-CT.

OBJECTIVE: This study aimed to explore 64-Copper-Chloride ( 64 CuCl 2 ) PET-CT in various malignancies and demonstrate a head-to-head comparison of uptake on 64 CuCl 2 PET/computed tomography (CT) and 18 fluorodeoxyglucose ( 18 FDG)-PET/CT scans for different malignancies, with an emphasis on 18 FDG nonavid malignancies. METHODS: Fifty-three patients diagnosed with various biopsy-proven malignancies (except prostate cancer) were recruited in this prospective study. All the patients underwent both 64 CuCl 2 PET/CT and 18 FDG-PET/CT. 64 CuCl 2 PET/CT was acquired at 1, 3 and 24 h time points. We studied the physiological biodistribution of 64 CuCl 2 in the various organs, corroborated the uptake of 64 CuCl 2 with various types of malignancies and comparison of their uptake with 18 FDG-PET/CT and their correlation with each other in various lesions. RESULTS: The biodistribution study showed that the liver concentrated 64 CuCl 2 the most out of all the organs, followed by the pancreas and large intestine. Liver and intestinal activity increased subsequently with delayed imaging, and the washout of 64 CuCl 2 was noted in the pancreas in delayed images and followed a hepatobiliary excretion of tracer over a period of time. In lesion-wise analysis, it was noted that the primary neuroendocrine tumor, melanoma and renal/urothelial malignancy group showed more uptake of 64 CuCl 2 , than that in metastasis and vice-versa was noted in lung and soft tissue malignancies. Comparing it with 18 FDG, it was seen that FDG showed more uptake in lesions and showed no significant correlation (Kappa value: 0.089) with the uptake of 64 CuCl 2 in the lesion-wise comparison. CONCLUSION: 64 CuCl 2 PET/CT did not show any added advantage over 18 FDG-PET/CT in the evaluation of the studied malignancies, both primary and their metastasis. Biodistribution studies showed the liver as the organ with maximum uptake, which implies it may hinder the detection of abdominal or hepatic involvement of the disease.

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.

Intricacies in the Preparation of Patient Doses of [177Lu]Lu-Rituximab and [177Lu]Lu-Trastuzumab Using Low Specific Activity [177Lu]LuCl3: Methodological Aspects.

The development of humanized monoclonal antibodies (MAbs) with Lutetium-177 ([177Lu]Lu3+) has brought a paradigm shift in the arena of targeted therapy of various cancers. [177Lu]Lu-DOTA-Rituximab and [177Lu]Lu-DOTA-Trastuzumab have gained prominence due to their improved therapeutic efficacy in the treatment of lymphoma and breast cancer. The clinical dose formulation of these radiolabeled MAbs, using low specific activity [177Lu]LuCl3, requires extensive optimization of the radiolabeling protocol. The present study merits the development of a single protocol which has been optimized for conjugation of Rituximab and Trastuzumab with p-NCS-benzyl-DOTA and further radiolabeling these immunoconjugates (ICs) with low specific activity [177Lu]LuCl3. Herein, we report a consistent and reproducible protocol for clinical dose formulations of [177Lu]Lu-DOTA-Rituximab and [177Lu]Lu-DOTA-Trastuzumab (~9.25 GBq each, equivalent to ~2 patient doses) with radiochemical yield (RCY) between 84 and 86% and radiochemical purities (RCP) >99%. The in vitro stabilities of both these radioimmunoconjugates (RICs) were retained up to 120 h post-radiolabeling, upon storage with L-ascorbic acid as stabilizer (concentration: ~ 220-240 µg/37MBq) at -20 °C. The ready-to-use formulation of clinical doses[177Lu]Lu-DOTA-Rituximab and [177Lu]Lu-DOTA-Trastuzumab has been successfully achieved by employing a single optimized protocol. While [177Lu]Lu-DOTA-Rituximab has exhibited a high degree of localization in retroperitoneal nodal mass of refractory lymphoma patient, high uptake of [177Lu]Lu-DOTA-Trastuzumab has been observed in metastatic breast carcinoma patient with multiple skeletal metastases.

68 Ga-PSMA-11 PET/CT and 64 CuCl 2 PET/CT Help in Identifying Rare Metastatic Site of Penile Shaft in a Patient of Carcinoma Prostate.

ABSTRACT: A 71-year-old man, presenting with complaints of burning sensation and pain during urination, finally diagnosed with prostate carcinoma. Ultrasonography of the abdomen and pelvis revealed prostatomegaly. Serum PSA level was elevated, and TRUS-guided biopsy demonstrated acinar adenocarcinoma (Gleason score: 5 + 4 = 9). 68 Ga-PSMA-11 PET/CT for initial staging showed PSMA-avid enlarged prostate, pelvic lymphadenopathy, and focal PSMA uptake in the left side of the shaft of the penis. The patient also underwent a 64 CuCl 2 PET/CT, which demonstrated similar findings of enlarged prostate and adenopathy with focally increased tracer uptake in the shaft of the penis coinciding with the lesion observed on 68 Ga-PSMA-11 PET/CT, thereby detecting a rare metastatic site from carcinoma prostate.

Middle Ear Cavity and Mastoid Neuroendocrine Tumor Presenting as Otomastoiditis with Cholesteatoma: A Clinicoradiological and Histopathological Correlation.

Neuroendocrine tumors of the middle ear are rare, comprising of less than 2% of primary tumors of the ear. The clinical and imaging findings of these tumors are nonspecific, and histological and immunohistochemical findings are confirmatory. Herein, we present a case of 48-year-old male, presenting with chief complaints of hearing loss of left ear with foul smelling discharge, with the initial clinical impression of otomastoiditis of the middle ear with cholesteatoma and being operated for the same, the final histopathology report inferred it as well-differentiated neuroendocrine tumor grade 1 with Ki-67 index less than 2%. Immunohistochemical examinations demonstrated positive staining of the tumor cells for cytokeratin, synaptophysin and chromogranin A, and negative for smooth muscle actin, desmin, S-100. The biochemical investigations showed raised serum chromogranin A levels. Based upon the findings on anatomical imaging modalities including high-resolution computed tomography temporal bone and magnetic resonance imaging paranasal sinuses (MRI PNS), the lesion was inferred inoperable due to involvement of dura of petrous apex, and therefore he was referred for consideration of peptide receptor radionuclide therapy (PRRT). MRI PNS also showed involvement of the horizontal part of facial nerve, indicating local aggressiveness of the tumor. 68 Ga-DOTATATE-PET/CT showed high-grade somatostatin receptor expressing soft tissue lesion involving middle ear and external auditory canal (Krenning's score 4), with low-grade metabolic activity on 18 F-FDG-PET/CT. The post-therapy scan following 177 Lu-DOTATATE PRRT, showed abnormal tracer concentration at the described site. Due to extreme rarity of this disease entity, it is important to accrue data for accurate diagnosis, proper management, and follow-up.

Association of Cutibacterium acnes with human thyroid cancer.

Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.

Application of Machine Learning in Predicting Hepatic Metastasis or Primary Site in Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) account for 80% of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). GEP-NETs are well-differentiated tumors, highly heterogeneous in biology and origin, and are often diagnosed at the metastatic stage. Diagnosis is commonly through clinical symptoms, histopathology, and PET-CT imaging, while molecular markers for metastasis and the primary site are unknown. Here, we report the identification of multi-gene signatures for hepatic metastasis and primary sites through analyses on RNA-SEQ datasets of pancreatic and small intestinal NETs tissue samples. Relevant gene features, identified from the normalized RNA-SEQ data using the mRMRe algorithm, were used to develop seven Machine Learning models (LDA, RF, CART, k-NN, SVM, XGBOOST, GBM). Two multi-gene random forest (RF) models classified primary and metastatic samples with 100% accuracy in training and test cohorts and >90% accuracy in an independent validation cohort. Similarly, three multi-gene RF models identified the pancreas or small intestine as the primary site with 100% accuracy in training and test cohorts, and >95% accuracy in an independent cohort. Multi-label models for concurrent prediction of hepatic metastasis and primary site returned >98.42% and >87.42% accuracies on training and test cohorts, respectively. A robust molecular signature to predict liver metastasis or the primary site for GEP-NETs is reported for the first time and could complement the clinical management of GEP-NETs.

68 Ga-PSMA-11 PET/CT Imaging in Brain Gliomas and Its Correlation With Clinicopathological Prognostic Parameters.

BACKGROUND: Gliomas are the most common primary central nervous system tumors, of which the malignant gliomas account for 60%-75%. The primary and secondary brain malignancies are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. The grade of gliomas, Ki-67 index, and IDH mutation status are among the major prognostic markers in gliomas. Prostate-specific membrane antigen (PSMA) is a zinc-dependent peptidase that is not only expressed in prostate cancer cells but also in the tumor neovasculature. The initial PSMA PET studies in central nervous system tumors using 68 Ga-HBED-CC-PSMA ( 68 Ga-PSMA-11) PET tracer confirmed selective target expression in gliomas of different grades, with higher expression in high-grade glioma compared with low-grade glioma. AIMS AND OBJECTIVES: The aim of the present study was to correlate and compare the 68 Ga-PSMA-11 and 18 F-FDG uptake in brain tumors with their clinicopathological prognostic parameters, so as to study their prognostic implications. In addition, the study also aimed to identify patients who are likely to benefit from potential PSMA-targeted therapies. PATIENTS AND METHODS: This ongoing prospective study was approved by the institutional scientific and medical ethics committee. The patients with primary or recurrent glioma lesions on MRI underwent regional brain PET/CT scanning with 68 Ga-PSMA-11 and 18 F-FDG. The final histopathology of the brain lesions (glioma grade), Ki-67 index, and IDH mutation status were compared with SUV max values of the 68 Ga-PSMA-11 and 18 F-FDG PET/CT. RESULTS: A total of 15 patients (13 males and 2 females; age range, 21-73 years; median age, 58 years) were included in this study analysis. Among the 15 patients, 10 were treatment naive and 2 were patients with recurrent glioma. Three patients turned out to be WHO grade I-II, 6 belonged to grade III, and 6 grade IV (glioblastoma multiforme) on final histopathology. The 68 Ga-PSMA-11 PET/CT showed tracer uptake in all high-grade gliomas with good tumor-to-background ratio. It was PSMA nonavid in 2/3 low-grade gliomas, and it showed low-grade uptake in 1/3 patients. PSMA expression (as evaluated by SUV max values) was significantly higher in higher-grade tumors, those with IDH mutation wildtype status, and higher Ki-67 indices. FDG PET SUV max also showed significant correlation with these prognostic parameters. CONCLUSIONS: In these preliminary results, PSMA PET appears to be an important tool in the evaluation and prognosis of gliomas. PSMA-directed theranostics can be explored as a personalized approach in gliomas with high PSMA uptake. However, with the limitation of small sample size, larger clinical trials are warranted to draw conclusive evidence regarding the same.

Testicular Metastasis From Neuroendocrine Tumors: Imaging and Theranostics Through 68 Ga-DOTATATE PET/CT and 177 Lu-DOTATATE-Based Peptide Receptor Radionuclide Therapy.

ABSTRACT: Neuroendocrine tumors (NETs) are rare neoplasms arising from enterochromaffin cells, which are predominantly noted in the gastrointestinal tract and lung; metastases of NETs to the testes in NET are further uncommon. Testicular NET usually has no symptoms and/or presents with painless swelling of the scrotum. Detection of testicular lesion can be challenging and frequently missed on conventional radiological imaging. We present testicular NET missed on conventional radiological imaging, where 68 Ga-DOTATATE PET/CT imaging detected the testicular lesion, and further evident on 177 Lu-DOTATATE-based post-peptide receptor radionuclide therapy theranostic imaging.

Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline.

PURPOSE: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Differentiation of Discordant Lesions on Dual-Tracer PET/CT (68Ga-PSMA-11 and 18F-FDG) in Prostate Carcinoma: Diagnosis of Second Primary Malignancies.

We present 2 cases of metastatic castration-resistant prostate carcinoma with discordant lesions on dual-tracer PET/CT (68Ga-PSMA-11 and 18F-FDG PET/CT), which on subsequent histopathologic evaluation revealed second primary malignancies of combined hepatocellular carcinoma and cholangiocarcinoma and poorly differentiated squamous cell carcinoma. These case illustrations emphasize the need to evaluate discordant lesions on dual-tracer PET/CT, which can lead to early diagnosis of second primary malignancies and thereby can provide better management in these patients.