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Abstract: Metastatic or recurrent adrenocortical carcinoma is a potentially lethal malignancy, presenting significant challenges in disease management owing to absence of effective systemic treatments. Significantly diminished survival rates necessitate rapid identification of specific molecules for the development of targeted therapeutics. Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts have been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. The effectiveness of various FAP inhibitors (FAPis) and FAP targeting peptide has been extensively documented in diverse clinical investigations. We have evaluated 3 molecules, that is, DOTA.SA.FAPi (SA.FAPi), FAPi46, and FAP2286, as potential theranostic probes for adrenocortical carcinoma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: We report a case of a 48-year-old man with recurrent hepatocellular carcinoma, who underwent FDG PET for restaging and demonstrated mildly tracer-avid arterial enhancing lesion in segment III (SUV max , 5.7). Owing to low FDG uptake, patient was planned for 68 Ga-SA.FAPi PET, which demonstrated higher tracer avidity in the lesion (SUV max , 24.4). Subsequently, patient underwent 177 Lu-microsphere SIRT (2.2 GBq) in segment III. The 3- and 6-month posttherapy SA.FAPi PET demonstrated an interval decrease in tracer uptake and size of treated lesion. This case highlighted the promising role of SA.FAPi PET in patient selection for 177 Lu-SIRT and subsequent response assessment., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: A monoclonal antibody, trastuzumab, is used for immunotherapy for HER2-expressing breast cancers. Large-sized antibodies demonstrate hepatobiliary clearance and slower pharmacokinetics. A trastuzumab fragment (Fab; 45 kDa) has been generated for theranostic use., Patients and Methods: Fab was generated by papain digestion. Trastuzumab and Fab have been radiolabelled with 177 Lu after being conjugated with a bifunctional chelating. The affinity and target specificity were studied in vitro. The first-in-human study was performed., Results: The bifunctional chelating agent conjugation of 1-2 molecules with trastuzumab and Fab was detected at the molar ratio 1:10 in bicarbonate buffer (0.5 M, pH 8) at 37°-40°C. However, 2-3 molecules of bifunctional chelating agent were conjugated when DMSO in PBS (0.1 M, pH 7) was used as a conjugation buffer at a molar ratio of 1:10. The radiolabelling yield of DOTA-conjugated Fab and trastuzumab at pH 5, 45°C to 50°C, with incubation time 2.5-3 hours was 80% and 41.67%, respectively. However, with DOTAGA-conjugated trastuzumab and Fab, the maximum radiolabelling yield at pH 5.5, 37°C, and at 2.5-3 hours was 80.83% and 83%, respectively. The calculated K d of DOTAGA Fab and trastuzumab with HER2-positive SKBR3 cells was 6.85 ± 0.24 × 10 -8 M and 1.71 ± 0.10 × 10 -8 M, respectively. DOTAGA-Fab and trastuzumab showed better radiolabelling yield at mild reaction conditions.177 Lu-DOTAGA-Fab demonstrated higher lesion uptake and lower liver retention as compared with 177 Lu-DOTAGA-trastuzumab. However, 177 Lu-DOTAGA-Fab as compared with 177 Lu-DOTAGA-trastuzumab showed a relatively early washout (5 days) from the lesion., Conclusions: 177 Lu-DOTAGA-Fab and trastuzumab are suitable for targeting the HER2 receptors., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Meningiomas are one of the major primary CNS tumors. Most meningiomas are benign, but rarely, these metastasize to distant organs, the lungs being the commonest site of metastasis. 18 F-FDG PET/CT has been used to evaluate metastatic pulmonary meningioma. However, 68 Ga-FAPI PET/CT has not yet been evaluated. The present case highlights the 68 Ga-FAPI uptake in metastatic pulmonary meningioma in a postoperated case of left tentorial meningioma presenting with lung masses. Image-guided biopsy from the lung mass was consistent with metastatic meningioma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Surgical resection is limited. Selective intra-arterial radionuclide therapy (SIRT) emerged as a potential cure for intermediate HCC with portal vein thrombosis. We report a pilot study of a 48-year-old man with recurrent HCC who underwent 177 Lu-microsphere SIRT (2.2 GBq) in segment III. Posttherapy SPECT/CT images (24 hours to 3 months) demonstrated excellent localization and prolonged retention within the tumor. Pre- and 3-month post-SIRT CECT showed a notable decrease in arterial enhancement and tumor size. Time-activity curve of the standard and the lesion demonstrated similar decay pattern indicating that 177 Lu-microspheres act as permanent implant., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Metastatic or recurrent adrenocortical carcinoma (ACC) is a potentially fatal malignancy, which poses major challenges in disease management owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for development of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.SA.FAPI (FAPI), as a potential diagnostic probe in 2 cases of histopathologically proven metastatic and recurrent ACC. Both patients underwent 18 F-FDG and 68 Ga-FAPI PET/CT scans for comparative analysis. 68 Ga-DOTA.SA.FAPI emerged as an excellent diagnostic agent for ACC and performed similar to 18 F-FDG., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Adrenocortical carcinoma (ACC) is a rare malignancy with a prevalence of 1 to 2 cases/million/year. The diagnosis depends upon endocrine workup followed by imaging with CT, MRI, and 18F-FDG PET/CT. The treatment includes surgical resection, debulking surgery, chemotherapy, and radiotherapy. However, patients do not respond well to any of the available therapies. We present noninvasive imaging of histopathology-proven ACC patients using 68Ga-DOTAGA-IAC PET/CT, specific for integrin αvβ3. 68Ga-DOTAGA-IAC PET/CT 45 minutes after IV injection showed a decent tumor-to-background ratio and could be used as a promising radiotracer for metastatic and recurrent ACC., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Duramycin, a 19 amino acids peptide, is known for its potential to target phosphatidylethanolamine. During cell death (apoptosis), rearrangement of membrane phospholipids results in the externalization of phosphatidylethanolamine to the outer leaflet of the cell membrane, which can be imaged using 68Ga-NOTA-duramycin. We report 68Ga-NOTA-duramycin imaging in a 50-year-old man with biopsy-proven diffuse large B-cell lymphoma planned for anthracycline-based chemotherapy. 68Ga-NOTA-duramycin PET/CT imaging along with 18F-FDG PET/CT was performed before and after 2 cycles of chemotherapy. The tracer avidity in interim 68Ga-NOTA-duramycin PET/CT showed its diagnostic potential to assess early response to chemotherapy., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This study was funded by the DST INSPIRE Fellowship, New Delhi, India (application reference no. DST/INSPIRE/03/2016/002649)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to compare the performance of angiogenesis-specific 68Ga-RGD2 PET/CT with Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) in assessing disease activity and treatment response in rheumatoid arthritis (RA)., Methods: This was a prospective study comparing the performance of 68Ga-RGD2 PET/CT and DAS28-ESR in 30 RA patients. All of them underwent 68Ga-RGD2 PET/CT scan from head to toe and clinical examination at the baseline. A repeat scan and clinical examination were done in 27 patients after 3 months of treatment with disease-modifying antirheumatic drugs ± steroids. Three PET parameters, that is, PJC (PET-positive joint count), aSUVmax (average SUVmax), and hSUVmax (highest SUVmax), of positive joints were compared with the DAS28-ESR for disease activity assessment and response evaluation., Results: Among the 3 PET parameters, PJC showed a significant correlation with the DAS28-ESR (0.64, P < 0.01). A significant change was observed with treatment in the DAS28-ESR and PET parameters of 27 patients at follow-up. There was significant correlation between percentage changes in DAS28-ESR and scan parameters such as PJC (0.689, P < 0.001), aSUVmax (0.712, P < 0.001), and hSUVmax (0.555, P = 0.003) values. The absolute change in aSUVmax value could accurately discriminate (area under the curve, 0.98; P = 0.001) European League Against Rheumatism responders from nonresponders., Conclusions: 68Ga-RGD2 PET/CT is a promising tool for objective assessment of disease activity and treatment response in patients with RA., Competing Interests: Conflicts of interest and sources of funding: This study was supported by the Indian Council of Medical Research, New Delhi, India (grant number 3/2/June-2017/PG-Thesis-HRD[23]). None declared to all authors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to assess the utility of presynaptic dopaminergic imaging using 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT and compare their performance in Parkinson's disease (PD), Parkinson-plus syndrome (PPS), and essential tremor (ET)., Patients and Methods: A total of 103 patients (PD = 48, PPS = 19, and ET = 36) were enrolled prospectively. Hoehn and Yahr (H&Y) staging and MDS-UPDRS (Movement Disorder Society-Sponsored Revision of Unified Parkinson's Disease Rating Scale) were done for PD and PPS cases. All the patients underwent 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT brain scan. The scans were analyzed visually and semiquantitatively. Average pixel count and SUVmean of the striatum were calculated in SPECT and PET images, respectively, to calculate the specific uptake ratio of striatum (SUR). Comparison of scan findings and SURs among different groups and correlation with clinical characteristics was done., Results: Symmetrical comma-shaped uptake was seen in bilateral striatum in ET cases with mean SURs significantly higher than in cases of early PD (H&Y stage I and II, n = 37), PD and PPS both on SPECT and PET images (P ≤ 0.001). The mean SURs between PD and PPS showed no significant difference (SPECT, P = 0.17; PET, P = 0.61). Substantial agreement (weighted κ = 0.659) was found between 99mTc-TRODAT-1 and 18F-FDOPA for the detection of presynaptic dopaminergic dysfunction. Specific uptake ratio of striatum correlation between SPECT and PET was statistically significant (r = 0.67; P < 0.01). A negative but nonsignificant correlation was found between the SURs and H&Y staging/MDS-UPDRS., Conclusions: Both 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT showed substantial agreement and proved to be potential imaging biomarker for the detection of dopaminergic dysfunction, thus assisting in differentiating early PD/PD and PPS from ET cases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Primary neuroendocrine tumor of the mediastinum is a relatively rare entity. In metastatic/inoperable disease, therapeutic options are limited to cytotoxic chemotherapy in poorly differentiated tumors and peptide receptor radionuclide therapy in case of well-differentiated tumors. We present the case of a 52-year-old man with mediastinal atypical carcinoid (grade II) neuroendocrine tumor showing mild somatostatin receptor expression and intense FDG avidity with progressive disease on chemotherapy. Chemokine receptor targeted PET/CT with CXCR4 (Ga-CXCR4) showed tracer avidity in tumor sites higher than the physiological sites, which may pave the way for CXCR4-targeted radionuclide therapy in this subgroup of patients.

Estrogen receptor-expressing breast cancer exhibits better prognosis due to responsiveness to antiestrogen treatment. Therefore, knowledge of the estrogen receptor status of a tumor is an important prognostic and predictive indicator in breast cancer. We present noninvasive imaging of estrogen receptors with Tc tamoxifen that can identify the active tumor and approachable sites for biopsy. It may help in selection of patients for hormone replacement therapy and in assessment of receptor status in recurrent disease and also in response evaluation.

Breast cancer is the most common cancer in women with rising incidence worldwide. F-FDG PET/CT imaging has already established itself as a pivotal modality for staging, restating and response assessment in patients with carcinoma breast. The complex biology of this cancer is increasingly being decoded and various molecular targets have been identified and exploited for guiding the treatment at various time points during the course of the disease. We here depict a series of various metabolic and receptor targeting PET radiotracers in breast cancer patients which may help us understand the in vivo biology of this tumor.

F-FDG PET/CT imaging is an important diagnostic tool for accurate staging and assessment of response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast carcinoma (LABC). However, F-FDG being non-specific marker, it also accumulates in inflammatory conditions, leading to false positive results. Angiogenesis, an essential characteristic for tumor development, intrusion and metastasis can be imaged using Ga-labeled RGD tripeptide. We here depict a series of clinically staged LABC patients who underwent both Ga-DOTA-RGD2 and F-FDG PET/CT imaging for staging and illustrate the similarities and significant differences between the two tracers.

Multiple-myeloma (MM) is a malignant plasma cell proliferation disorder and the second most common blood malignancy after non-Hodgkin lymphoma. The chemokine (CXCR-4) receptor analogues are the newer agents being postulated for myeloma imaging and have shown good diagnostic performance. We report a case of plasmacytoma with suspicious renal cell carcinoma, in whom Ga CXCR-4 PET/CT revealed tracer-avid lesion in the left perinephric region. PET/CT-guided biopsy from the tracer-avid lesion revealed plasmacytoma. PET/CT-imaging and guided biopsy using Ga CXCR4 receptor ligand, proved its usefulness for accurate localization of the culprit lesion and helped in definitive management of the patient.

Persistent hyperinsulinemic hypoglycemia in adults is most commonly caused by insulinomas, which pose a diagnostic challenge to physicians, surgeons, and radiologists and require multimodality imaging for precise localization and staging. PET tracers such as F-FDOPA and glucagon-like peptide 1 receptor analogs have been used for imaging insulinomas. Glucagon-like peptide 1 receptor analogs have recently shown promising results in preoperative localization of these tumors, as all insulinomas express glucagon-like peptide 1 receptors. Ga-DOTA-Exendin PET and MRI done in the present case helped in precise localization and management of the culprit lesion, whereas contrast-enhanced CT and F-FDOPA PET failed to do so.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. Often, patients present with inoperable and advanced disease. Selective internal radionuclide therapy offers prolonged survival and improved quality of life by delivering high radiation dose to the tumor with minimal complications. We report 2 inoperable cases of HCC treated with therapeutic dose of indigenously developed Re microspheres delivered to the hepatic lesions by transarterial catheterization. Follow-up CT revealed necrosis within the lesion, suggesting response to selective internal radionuclide therapy. Re microspheres may be a potential treatment option for inoperable HCC with or without portal vein thrombosis.

Here we report a 31-year-old man with a peri-ampullary neuroendocrine tumor (NET), who underwent Ga DOTANOC-PET/CT for recurrence evaluation, which revealed isolated metastatic lesion in liver segment V. He underwent trans-arterial radio-embolization (TARE) of the isolated hepatic metastasis with Rhenium-microspheres in a lipiodol matrix. The second Ga DOTANOC-PET/CT was performed one month after the TARE therapy revealed resolution of the tracer uptake with good retention of the lipiodol complex replacing the metastasis suggesting a complete response.

Insulinomas are the most common functioning pancreatic neuroendocrine tumors and the leading cause of persistent hypoglycemia with hyperinsulinemia in adults. Glucagon-like-peptide-1 (GLP) receptor analogs are the latest agents being used in the detection of insulinomas, with initial reports suggesting high sensitivity due to universal GLP1 receptor expression on these tumors. PET/CT imaging in this patient using Ga DOTA-Exendin, a GLP receptor analog, proved useful for accurate localization of the culprit lesion, aiding in the definitive management of the patient.

Metastatic jugular paraganglioma are rare tumors and account for less than 1% of the cases of head and neck tumors. We report a 40-year-old woman of jugular paraganglioma, presenting with right-sided neck swelling, hearing loss, and pulsatile tinnitus. Contrast-enhanced CT temporal bone revealed a mass in the right jugular foramina and extending inferiorly to internal jugular vein. Ga DOTANOC PET/CT was performed, which revealed somatostatin receptor expressing lesion in the right internal jugular vein and extension into sigmoid sinus and additional metastatic focus in the sacrum.

Urinary bladder paraganglioma constitute only a small fraction of urinary bladder tumors. These rare tumors are well known for recurrences even after many years of surgery. Functional imaging with different radiotracers has been found to be useful to evaluate the extent, metastasis, and recurrence of paragangliomas. We report a case where Ga DOTANOC PET/CT successfully detected recurrence of a paraganglioma in the urinary bladder along with pelvic lymph nodal metastasis.

Neurolymphomatosis, a rare extranodal lymphoma, may involve the cranial nerves, peripheral nerves, spinal nerve roots, or nerve plexus. F-FDG PET/CT however shows increased FDG uptake in the nerves but is not specific for malignancy. We report a patient with neurolymphomatosis who underwent F-FDG PET/CT and F-fluorothymidine PET/CT where both the scans showed increased tracer uptake in the right sciatic nerve, proven later as neurolymphomatosis on nerve biopsy. Furthermore, the F-FDG avid mediastinal lymph nodes did not show F-fluorothymidine avidity, suggesting an inflammatory etiology.

Pancreatic neuroendocrine tumors (PNETs) represent a small percentage of all pancreatic malignancies, and most of these present as metastatic disease. Somatostatin receptor scintigraphy had been used successfully for the assessment of patients with NET. Somatostatin receptor scintigraphy is indispensable for localization of ectopic NET and the distribution of NET throughout the body.

Malignant melanoma is an aggressive tumor with poor prognosis that can have widespread metastases at presentation. Melanoma is known to undergo neuroendocrine differentiation. We report a case of a 60-year-old woman with malignant melanoma showing a metastatic lesion in the thyroid expressing somatostatin receptors as evident by Ga-DOTANOC PET/CT and metabolically active widespread subcutaneous metastases on F-FDG PET/CT imaging.

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small benign mesenchymal tumors. The localization of these tumors is challenging, however, essential for the management. We compared the utility of F-FDG PET/CT and Ga DOTATATE PET/CT to detect the site of primary tumor in patients with suspicion of TIO., Patients and Methods: Retrospective analysis of 6 patients with hypophosphatemic osteomalacia and suspicion of TIO was performed. Ga DOTATATE PET/CT study was performed in all 6 patients to localize the tumor. F-FDG PET/CT was performed in 4 of 6 patients. F-FDG and Ga DOTATATE PET/CT studies were performed within 1 week of each other. Both studies were interpreted blindly without the knowledge of other imaging findings., Results: All patients had symptoms of osteomalacia and hypophosphatemia. All except 1 patient had increased level of fibroblast growth factor 23. The lag time (symptoms to PET diagnosis) ranged from 1.5 to 22 years. In 4 patients, where both studies were performed, F-FDG and Ga DOTATATE PET/CT were able to localize the tumor in 2 and 3 patients. Ga DOTATATE PET/CT detected tumor in 5 (83.3%) of 6 patients., Conclusions: Ga DOTATATE PET/CT performed better than F-FDG PET/CT and is useful in the detection of tumors causing oncogenic osteomalacia. Therefore, in clinically suspected cases of hypophosphatemic osteomalacia, Ga DOTATATE PET/CT may be performed as first-line imaging investigation to avoid delay in the treatment of this devastating but curable disease. However, further studies with large patient population are warranted to validate our data.

Solitary fibrous tumors (SFTs) are rare group of mesenchymal tumors that occurs predominantly in the pleura. The role of PET/CT imaging in characterizing the SFT is not well reported. Mesenchymal tumors may express somatostatin receptors. We hereby report a rare case of SFT of the nasopharynx showing Ga DOTATATE avidity.

The coexistence of a pituitary neoplasm and pheochromocytoma is a rare condition, which may be another undefined variant of Multiple endocrine neoplasia (MEN) syndrome. Moreover, the coexistence of pituitary macroadenoma and multiple paragangliomas is more uncommon and only few authors have reported these findings. We are reporting the use of Ga DOTATATE PET/CT in a rare case of coexisting pituitary macroadenoma and multiple paragangliomas.