Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study.

PURPOSE: Despite the existence of various treatment options, the prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unfavorable. One potential therapeutic approach is the use of [225Ac]Ac-PSMA-617, a targeted alpha therapy (TAT) that administers alpha-particle radiation specifically to prostate cancer cells expressing PSMA. In this study, we report the long-term survival outcomes of this novel therapy in a series of patients with mCRPC who have exhausted all standard treatment options. METHODS: The study enrolled patients with mCRPC who had shown resistance to standard lines of therapies, including next-generation anti-androgen therapies and taxane-based chemotherapies. These eligible patients received treatment with [225Ac]Ac-PSMA-617 at 100-150 kBq/kg doses administered every 8 weeks. The primary objective of the study was to assess overall survival (OS), while secondary objectives included evaluating radiological progression-free survival (rPFS), monitoring serum prostate-specific antigen (PSA) levels as a measure of biochemical response, and assessing adverse events using the CTCAE v5.0 grading system. RESULTS: Among the 63 initially enrolled patients, a total of 56 patients who had completed at least two cycles of [225Ac]Ac-PSMA-617 were included in this study. The mean age was 67 years (range, 39-87) and patients received a total of 204 cycles of [225Ac]Ac-PSMA-617 TAT. 91% of patients exhibited any PSA decline, with 67.8% experiencing a decline of 50% or more. The median follow-up was of 22 months (range: 6-59 months). Imaging-based disease progression was observed in 68% of patients, and 66% of patients succumbed to the disease. The median OS was 15 months (95% CI: 10-19). In univariate analysis, factors such as lack of >50% PSA decline (P=0.031), Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher (P=0.048), and radiological progression (rPD) (P<0.001) were found to be predictors of poor OS. However, in multivariate analysis, only rPD emerged as an independent prognostic factor with a hazard ratio (HR) of 8.264 (95% CI: 1.429-16.497, P=0.004). The estimated median rPFS was 9 months (95% CI: 7-15). Moreover, patients who demonstrated any PSA decline had a median rPFS of 10 months compared to only 3 months in patients without any PSA decline (multivariate HR: 6.749; 95% CI: 1.949-23.370; P=0.002). Fatigue was one of the most common treatment-emergent adverse events, with grades 1/2 occurring in 70% of patients and grades 3 or higher in 3.5% of patients. This fatigue was transient and resolved before the next treatment cycle. Additionally, approximately one-third of patients experienced xerostomia (grades 1/2: 32.1%). CONCLUSION: [225Ac]Ac-PSMA-617 targeted alpha therapy, was found to be well-tolerated with acceptable adverse events and effective in the treatment of patients with end-stage mCRPC.

Late Local and Distant Recurrence of Apparently Benign Paraganglioma.

Paraganglioma-pheochromocytoma (PPGLs) are relatively rare catecholamine-secreting tumors of chromaffin origin. Due to the sympathetic effects of catecholamine excess, their presentation may range from non-specific symptoms to dangerous hypertensive crises. We present the case of a 36-year-old lady with recurrent paraganglioma (PGL) who presented in emergency with hypertensive crisis. She had a history of surgery for left-sided PGL 18 years earlier. Imaging showed local recurrence with pulmonary metastases and blood biochemistry showed raised urinary metanephrines. In view of her poor general condition, we undertook a staged surgical approach for management. She first underwent en-bloc excision of recurrent PGL with left nephrectomy. Nine weeks later, she underwent a pulmonary metastasectomy. This staged surgical approach resulted in the stabilization of blood pressure and normalization of urinary catecholamine. Although most of these tumors are indolent by nature, this case highlights the metastatic potential of apparently benign PGL. This case explores the possibility of a staged surgical approach in a high-risk patient and emphasizes the need for long-term follow-up in these cases.

18F-FDG PET/CT in cyst infection in autosomal dominant polycystic kidney disease.

Infection of a cyst within an autosomal dominant polycystic kidney disease (ADPKD) is a serious complication. Diagnosis with conventional imaging techniques such as ultrasonography, computed tomography (CT), and magnetic resonance imaging can be sometimes challenging. The definite diagnosis is analysis of the cyst fluid, but cyst punctures can cause bleeding, rupture, and contamination of adjacent cysts. Recently, FDG PET/CT has been reported as a sensitive tool for detection of cyst infection. We describe a case of 63-year-old woman with infected cysts in the left kidney, in whom accurate diagnosis was made on FDG PET/CT. FDG PET/CT is an important investigation in patients with fever of uncertain etiology, where renal cyst infection is a possible cause, but other etiologies also need to be ruled out.

DOES LOSS OF 131I COUNTS NEED CORRECTION IN GAMMA-CAMERA IMAGING IN CHILDREN AND YOUNG ADULTS IN POST-THERAPEUTIC SCANS? COMPARISON OF PHANTOM VERSUS PATIENT STUDY.

This study aimed to verify whether there is whole-body (WB) count loss due to dead time of gamma camera when high amount of 131I is administered to patients. Planar views of a phantom containing 5751 MBq of 131I were acquired at 24-h intervals for 68 d. Eighty-two patients ≤21 y old were given diagnostic activity (74 MBq) followed by therapeutic activity (1110-5772 MBq). WB scans of patients were acquired at 2 h after diagnostic and therapeutic activity administration. Count loss in patients and phantom were compared. In phantom, there was no count loss up to 139 MBq. At maximum activity of 5751 MBq 131I, the loss was 46%. In patients, the average WB count loss was insignificant after the administration of therapeutic activity. Count loss due to dead time in phantom differed significantly from patient results that can probably be explained by the distribution of activity over a large area in vivo.

SMARCB1 (INI1)-deficient thyroid carcinoma: A novel entity expanding the spectrum of tumors with INI1 loss.

BACKGROUND: Biallelic loss of SMARCB1/INI1 is associated with highly aggressive malignancies, namely renal and extra-renal malignant rhabdoid tumors, and atypical teratoid/ rhabdoid tumor. Increasing availability of molecular testing and immunohistochemical stains acting as surrogate tools to genetic analysis has led to an increasing recognition of SMARCB1 loss in a variety of neoplasms. Interestingly, many of these lack the typical rhabdoid features ascribed to this group of tumors, making their identification difficult. CASE PRESENTATION: We describe the cytological, histological, immunohistochemical and molecular features of the first case of primary SMARCB1 (INI1)-deficient carcinoma of the thyroid gland in literature. The tumor was unique in various aspects; apart from never having been documented at this location, it showed extensive glandular differentiation, mimicking metastatic adenocarcinoma. CONCLUSION: Awareness of this novel entity is essential to avoid misdiagnosis, and for appropriate management, especially in an era of increased feasibility of targeted therapy.

Orbital IgG4 Disease: Imaging Findings on 68Ga-DOTANOC PET/CT.

Immunoglobulin G4 (IgG4)-related diseases are a spectrum of systemic inflammatory conditions of unknown etiology, which are characterized by infiltration of tissues by IgG4 plasma cells and sclerosing inflammation (Cheuk and Chan Adv Anat Pathol 17:303-32, 2010). Although this condition was initially described in relation to autoimmune pancreatitis, now it has been reported in almost every organ system of body (Zen and Nakanuma Am J Surg Pathol 34:1812-9, 2010, Masaki et al. Ann Rheuma Dis 68:1310-5, 2009). Orbital involvement by IgG4 disease can involve extraocular muscles (EOM), lacrimal glands, conjunctiva, eyelids, infraorbital nerve, orbital fat, and nasolacrimal system (McNab and McKelvie. Ophthal Plast Reconstr Surg 31:167-78, 2015, Katsura et al. Neuroradiology 54:873-82, 2012). The basis of using 68Ga-DOTANOC PET/CT in IgG4 orbital disease is the known expression of somatostatin receptors in chronic inflammatory cells (Cuccurullo et al. Indian J Radiol Imaging 27:509-16, 2017) and also avidity shown previously in other IgG4-related diseases (Cheng et al. Clin Nucl Med 43:773-6, 2018).

Fluorocholine PET Imaging of Parathyroid Disease.

To give an overview of the potential clinical utility of 18F-fluorocholine PET/CT (FCH PET/CT) in imaging of parathyroid adenoma. Available studies have provided preliminary results of 18F-FCH PET/CT in primary and secondary hyperparathyroidism. Results of various studies have shown that 18F-FCH is a promising upcoming tracer for the detection of parathyroid adenomas, especially when multiple, or having low size. FCH PET/CT has the potential to be a standard investigation in the detection of parathyroid lesions.

Assessment of the role of early dynamic PET/CT with 18F-fluorocholine in detection of parathyroid lesions in patients with primary hyperparathyroidism.

OBJECTIVE: The aim of the present study was to assess the utility of early dynamic PET/computed tomography with fluorine-18-fluorocholine (F-FCH) in detecting parathyroid lesions and in differentiating parathyroid lesions from cervical lymph nodes (LNs). PATIENTS AND METHODS: A prospective study was conducted on 14 patients with clinical and biochemical evidence of primary hyperparathyroidism by having a positive Tc-sestaMIBI scan. Patients underwent early dynamic F-FCH PET/computed tomography scan, after the administration of 5-8 mCi (185-296 MBq) at 1 min per frame for 15 min. Delayed static images of 2-3 min per bed position were taken between 45 and 60 min. 3D-VOI's were plotted on parathyroid adenoma, cervical LN and thyroid. Dynamic and static images were interpreted by two expert nuclear medicine physicians independently and the following parameters were calculated for parathyroid adenoma and cervical LN: maximum standardized uptake value (SUVmax), time activity curve for SUVmax, t-peak. Adenoma to thyroid ratio (A/T) and cervical LN to thyroid ratio were calculated for each dynamic and static image. RESULTS: Fourteen (eight females and six males) patients were included in the study. All patients showed a higher SUVmax in the adenoma and the cervical LN in the early dynamic images as compared with delayed static images. A/T ratio obtained in the dynamic and static images were compared and found to have insignificant difference (P=0.2255). The difference between mean A/T and LN to thyroid ratio was found to be significant (P=0.0117) during the dynamic study. CONCLUSION: A possible explanation of higher SUVmax in the dynamic images in adenomas may be due to the increased vascularity/early F-FCH uptake. Results indicate early dynamic imaging could suffice, without the need for a delayed image after 45 min, and this technique could adequately differentiate a parathyroid adenoma from a cervical LN.

Somatostatin Receptor PET/CT Features of Carcinoid Heart Disease.

We present the case of a 35-year-old woman with metastatic neuroendocrine tumor undergoing treatment with long-acting octreotide and Lu-DOTATATE therapy. We present features of carcinoid heart disease on Ga-DOTANOC PET/CT, which revealed dilated right atrium, pericardial effusion, ascites, and congestive hepatopathy apart from the metastatic lesions in the liver. The scan cardiac findings were confirmed by echocardiography. This highlights the significance of identifying such patients early because additional management is required for carcinoid heart disease per se and a cautious approach is needed in administering amino acid infusion during PRRT that can result in fluid overload.

Cytological features of warthin-like papillary thyroid carcinoma: A case report with review of previous cytology cases.

Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC.

Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study.

PURPOSE: The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors. METHODS: One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-DOTANOC PET/CT scans. Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively. RESULTS: There was no significant difference in the hemoglobin levels after Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/µL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression. CONCLUSIONS: Addition of capecitabine therapy with Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.

Post-therapeutic dosimetry of 177Lu-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients. MATERIALS AND METHODS: After obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60 min before Lu-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.52±1.3 GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168 h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software. RESULTS: A total of 26 mCRPC patients with a mean age of 66.30±9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24±0.26 and 0.99±0.31 mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36±0.10, 0.243±0.09 and 0.048±0.05 mGy/MBq, respectively. The mean whole-body dose was 0.016±0.003 mGy/MBq. CONCLUSION: Lu-DKFZ-PSMA-617 therapy is a safe option in the treatment of mCRPC patients.

Practical experience and challenges in the operation of medical cyclotron.

OBJECTIVE: The aim of this article was to share 10 years of operational experience of medical cyclotron and to provide working knowledge on the same. This experience has helped us gain working knowledge on cyclotron operation with practical points, which may help in improving F yield, minimizing the breakdown time, and help in the prevention of the occurrence of unusual events. MATERIALS AND METHODS: Our facility has a self-shielded radioisotope delivery system eclipse 111 medical cyclotron with an 11 MeV proton beam in use for the past 10 years to produce positron emitters - namely, F, N, and F-2 gas - for PET imaging. During F production, we have followed a set protocol comprising the following: monitoring target pressure, rinsing the target with O water just immediately after bombardment, ion source feedback, radiofrequency (RF) feedback, and recording any unusual events that occurred during the operation. Besides this, enrichment of O water, target volume, target current, energy of the beam, variation in argon pressure on the target, bombardment duration, target status (new or old target or total number of previous bombardments on the same target), status of the delivery lines from target to the radiochemistry module (old or new) were also recorded. RESULTS: Rinsing with O water immediately after bombardment increases the life of the target and delivery line. The frequent problems encountered were with the ion source, RF, and target foil rupture. These problems were solved by rebuilding the ion source, changing the fuse of RF, and rebuilding the target. CONCLUSION: F yield can be increased by rinsing with O water immediately after bombardment. The effect of target leak - that is, rupture of vacuum window - can be avoided by immediate stoppage of bombardment.

Comparison of 18F-Fluorocholine Positron Emission Tomography/Computed Tomography and Four-dimensional Computed Tomography in the Preoperative Localization of Parathyroid Adenomas-initial Results.

OBJECTIVE: We aimed to compare the diagnostic accuracy of 18F-Fluorocholine (FCH)-positron emission tomography/computed tomography (PET/CT) and four-dimensional (4D)- CT in detection and localization of eutopic and ectopic parathyroid adenoma (PA) in patients with hyperparathyroidism. MATERIALS AND METHODS: Five patients with primary hyperparathyroidism underwent FCH-PET/CT after 60 min of 185 MBq of intravenous 18F-FCH administration. Images were acquired from head to mediastinum at 3 min per bed position. No intravenous contrast was used. All patients underwent 4D-CT within 2 weeks of the FCH-PET/CT, with a precontrast, post contrast arterial, and venous phase with 75 ml intravenous Iohexol 350 followed by 25 ml saline chase. Histopathology was considered as the gold standard. RESULTS: Both modalities showed 100% concordance in the detection of parathyroid lesions. Both FCH-PET/CT and 4D-CT detected 7 lesions in 5 patients, with 4 patients having a single lesion, and 1 patient having three lesions. Of the 7 reported lesions, 4 were eutopic and 3 were ectopic. No additional lesions were detected by either modality in comparison to the other. All 7 specimens were resected and histopathology showed PA/hyperplasia. CONCLUSION: FCH-PET/CT and 4D-CT are equally efficacious in detection and localization of eutopic and ectopic PA. This may open up the possibility of using FCH-PET/CT in patients with negative conventional imaging who cannot undergo contrast studies.

Parathyroid carcinoma with contralateral subcutaneous and breast recurrences: A rare presentation.

BACKGROUND: Parathyroid carcinoma is extremely rare. Correct preoperative and even histopathological diagnosis may be difficult owing to the deceptively bland cytoarchitectural features, especially when presenting with localized disease. Recurrence/metastases developing years later then make the malignant nature obvious. METHODS AND RESULTS: We present here an unusual case of a 32-year-old patient with carcinoma of the left upper parathyroid gland, initially diagnosed as parathyroid adenoma, treated with endoscopic left parathyroidectomy, and later developing subcutaneous metastatic nodules over the medial end of the right clavicle and right anterior chest wall, followed by a right breast deposit. The recurrences, especially subcutaneous ones, were probably secondary to tumor seeding along the track of insertion of the endoscope. CONCLUSION: Involvement of subcutaneous tissue and the breast in parathyroid carcinoma is extremely rare. The case is being reported for its uniqueness along with a discussion of possible appropriate course of management, which may have averted the aggressive clinical course of the disease.

99mTc-DMSA planar imaging versus dual-detector SPECT for the detection of renal cortical scars in patients with CKD-3.

OBJECTIVE: The aim of this study was to compare planar technetium-99m-dimercaptosuccinic acid (Tc-DMSA) cortical scintigraphy with Tc-DMSA single-photon emission computed tomography (SPECT) for the detection of renal cortical scars in patients with chronic kidney disease stage-3 (CKD-3). PATIENTS AND METHODS: Data of 40 patients (mean age: 43.7±15.3 years, 29 men, 11 women) who underwent planar Tc-DMSA along with regional Tc-DMSA SPECT for the detection of renal cortical scars were prospectively evaluated. All the patients had CKD-3, with a mean serum creatinine level of 2.23±1.85 g/dl. Planar and SPECT Tc-DMSA images were evaluated by two nuclear medicine readers independently. Each kidney was divided into 12 cortical segments. A cortical segment was recorded as abnormal if it had reduced or absent radiotracer activity. The linear correlation coefficient (r value) for the number of abnormal segments detected between readers was calculated for planar imaging, SPECT, and between the two techniques for both the readers. RESULTS: For both observers, the average correlation coefficient for SPECT (r=0.87) and planar imaging (r=0.90) was high (P<0.0001). A moderately strong linear correlation was also observed between readers for planar imaging and SPECT (r=0.78 and 0.71, P<0.0001). There was no significant difference in the average number of abnormal segments detected by planar versus SPECT imaging: 2.1 for planar imaging and 2.8 for SPECT (P=0.06, two-tailed). In 15% of patients, SPECT detected cortical defects not appreciated on planar imaging. CONCLUSION: Tc-DMSA renal cortical imaging using dual-head SPECT offers no statistically significant diagnostic advantage over planar imaging for the detection of cortical defects in patients with CKD-3.

Hemimegalencephaly: A rare cause of hemihypoperfusion on 99m technetium-ethyl cysteinate dimer brain perfusion single-photon emission computed tomography.

Hemimegalencephaly is a rare congenital neuronal migration disorder that can presents with the equally rare finding of hemihypoperfusion on brain perfusion single-photon emission computed tomography (SPECT). It is an extremely rare cause of intractable epilepsy. Technetium-99m ethyl cysteinate dimer (ECD) brain perfusion SPECT is useful in excluding other foci of hypoperfusion in the contralateral since hemispherectomy has been suggested to be the treatment of choice. Furthermore, hemimegalencephaly may present with hyper as well as hypoperfusion on ECD SPECT. We present the case of an 11-year-old male child with intractable seizures who showed hemihypoperfusion in the hemimegalecephalic hemisphere.