Publications by authors named "Chandrasekhar Bal"

286 Publications

Long-term outcome of 177Lu-PSMA-617 radioligand therapy in heavily pre-treated metastatic castration-resistant prostate cancer patients.

PLoS One 2021 10;16(5):e0251375. Epub 2021 May 10.

Department of Nuclear Medicine, Thyroid Clinic, AIIMS, Ansari Nagar, New Delhi, India.

Objective: Investigators have extensively explored the short-term safety and efficacy data on 177Lu-PSMA-617 radioligand therapy (RLT) in mCRPC patients. However, scarce literature is reported on the long-term outcome of these patients. The current goal of this study is focused on the long-term outcome of mCRPC patients treated with 177Lu-PSMA-617 RLT.

Methods: Among 135 patients, 121 mCRPC patients fulfilled the eligibility criteria and were included in the final analysis. Patients received a median of 3 cycles of 177Lu-PSMA-617 RLT at 6 to 12-week intervals. Primary endpoint included overall survival (OS) and secondary endpoints involved progression-free survival (PFS), predictive factors of OS and PFS, PSA response rate, molecular response, clinical response, and toxicity assessment.

Results: The median administered cumulative activity was 20 GBq (3.7-37 GBq). The median follow-up duration was 36 months (6-72 months). The estimated median PFS and OS were 12 months (mo) (95% CI: 10.3-13 mo) and 16 mo (95% CI: 13-17 mo), respectively. Any PSA decline and PSA decline >50% was achieved in 73% and 61% of the patients, respectively. Multivariate analysis revealed only failure to achieve >50% PSA decline as a significant factor associated with a poor PFS. Prognostic factors associated with reduced OS included, failure to experience >50% PSA decline, heavily pre-treated patient cohort who received >2 lines of prior treatment options, and patient sub-group treated with ≥2 lines of chemotherapy. Patients re-treated with additional treatment options after attaining 177Lu-PSMA refractory disease showed a remarkably prolonged OS. A significant clinical benefit was achieved post 177Lu-PSMA-617 RLT. The most common toxicities observed were fatigue (34.7%), followed by nausea (33%), and dry mouth (24.7%).

Conclusion: The current study supports the short-term safety and efficacy results of high response rates, prolonged PFS and OS, improved quality of life, and low treatment-related toxicities in patients treated with 177Lu-PSMA-617 radioligand therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251375PLOS
May 2021

Ac-PSMA-617-targeted alpha therapy for the treatment of metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.

Prostate 2021 Jun 27;81(9):580-591. Epub 2021 Apr 27.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Background: The aim of this systematic review and meta-analysis was to present an overview of the role of Ac-PSMA (prostate-specific membrane antigen)-targeted alpha therapy (TAT) as a salvage treatment option in metastatic castration-resistant prostate cancer.

Methods: A systematic literature review was performed in databases such as Medline, Embase, PubMed, Cochrane Central Register of Controlled Clinical Trials, and the website; www.ClinicalTrials.gov until December 2020. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. All original articles, including retrospective, prospective, hand-searched articles, and clinical trials, were searched, and appropriate data were included for the analysis. The study's primary endpoint assessed therapeutic efficacy by biochemical response assessment criteria (any prostate-specific antigen [PSA] decline and >50% PSA decline from the baseline) after Ac-PSMA-TAT. The secondary endpoints included assessing overall survival (OS), progression-free survival (PFS), molecular response, and therapy-related adverse events across all the studies. The values were expressed as pooled proportions and demonstrated graphically by forest plots using the random-effects model.

Results: After the data extraction and filtration process, a total of three publications, including 141 patients, were included for the final analysis. The pooled proportion of patients demonstrating any PSA decline and greater than 50% PSA decline were 83% (95% confidence interval [CI]: 77%-89%) and 59% (95% CI: 42%-76%), respectively. The pooled proportions for OS was 81% (95% CI: 74%-89%). The pooled proportion of patients who have shown complete molecular response are 17% (95% CI: 5%-29%). The median PFS was 12 months (interquartile range: 8.2-14.4 months). Across the studies, the most common side effects from Ac-PSMA-617 TAT were xerostomia/dry mouth, which pertained to Gr I-II in 63.1% (89 of 141), followed by fatigue in 44.5% (45 of 101) of patients. Grade I-II and III anemia was noted in 48.5% (49 of 101) and 6% (6 of 101), respectively. Grade III leukopenia and thrombocytopenia were negligible: 0.9% (1 of 101) and 0.9% (1 of 101), respectively. Similarly, grade III nephrotoxicity was also observed only in 5 of 101 (5%) patients.

Conclusion: Treatment with Ac-PSMA-617 TAT demonstrated biochemical response, improved survival, caused low treatment-related toxicity proving a promising salvage treatment option in mCRPC patients.
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http://dx.doi.org/10.1002/pros.24137DOI Listing
June 2021

F-18 ML-104 tau PET imaging in mild cognitive impairment.

Nucl Med Commun 2021 Apr 9. Epub 2021 Apr 9.

Department of Nuclear Medicine Department of Neurology, CN Centre Department of Geriatrics, AIIMS, New Delhi, India.

Objective: This study was undertaken to evaluate the tau distribution patterns in patients with amnestic mild cognitive impairment (aMCI) using PET radiotracer F-18 ML-104.

Materials And Methods: Thirty patients, clinically diagnosed as aMCI [mini mental state evaluation ≥24] in the neurology or geriatric memory clinics, were included in the study. Each aMCI patient underwent F-18 fluorodeoxyglucose and F-18 ML-104 tau PET. Standardized uptake value ratios for cortical gray matter regions were evaluated for F-18 ML-104 tau PET and compared with normal controls and with early Alzheimer's disease (AD) patients (used from a previous study).

Results: aMCI revealed significantly higher standardized uptake value ratios in both medial temporal cortices, precuneus and posterior cingulate cortices in comparison to normal controls and a significantly lesser binding in bilateral medial and lateral temporal, precuneus and posterior cingulate cortices in comparison to early AD. A negative correlation was noted between F-18 fluorodeoxyglucose uptake and F-18 ML-104 retention in the precuneus and posterior cingulate cortices in aMCI, while F-18 ML-104 retention and mini mental state evaluation scores revealed a moderate negative correlation in the posterior cingulate cortices.

Conclusion: We could demonstrate a significant increase in cortical tau deposition in aMCI patients in comparison to normal controls, thus providing in vivo evidence of the underlying pathological process in this subgroup of patients with high probability of conversion to AD.
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http://dx.doi.org/10.1097/MNM.0000000000001415DOI Listing
April 2021

Thoracic Extradural Paraganglioma Localized on 68Ga-DOTANOC PET/CT.

Clin Nucl Med 2021 Apr 5. Epub 2021 Apr 5.

From the Departments of Nuclear Medicine Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India.

Abstract: We present the case of a 33-year-old woman with complaints of headache and palpitations with raised urinary catecholamines. Ultrasound of the abdomen was noncontributory, and the patient was referred for 68Ga-DOTANOC PET/CT, which revealed tracer accumulation in the thecal sac/spinal canal at D5-D7 level, suggestive of a thoracic paraganglioma. MRI of the spine subsequently confirmed the presence of an extradural mass in the spinal canal extending from D4 to D8.
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http://dx.doi.org/10.1097/RLU.0000000000003643DOI Listing
April 2021

Is There Any Need for Adjusting I Activity for the Treatment of High Turnover Graves' Disease Compared to Normal Turnover Patients? Results from a Retrospective Cohort Study Validated by Propensity Score Analysis.

Nucl Med Mol Imaging 2021 Feb 7;55(1):15-26. Epub 2021 Jan 7.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, 110029 India.

Purpose: To compare I-therapy outcomes in high turnover and normal turnover Graves' disease patients and predict optimal first I activity for high turnover patients.

Methods: Retrospective cohort design (1:2) validated by propensity score analysis. Cohort 1, high turnover (2-h RAIU/24-h RAIU ≥ 1),  = 104, and cohort 2, normal turnover (ratio < 1),  = 208, patients were compared for post I outcome. The cure was defined as a combined euthyroid and stable hypothyroid state following I treatment. Logistic regression analysis was used for identifying prognostic factors. The propensity score was applied; 77 matched pairs (1:1 ratio) of high and normal turnover patients were selected as a validation set.

Results: First I cure rates of 28% in high turnover and 66% in normal turnover groups ( = 0.001) were noted. The therapy cycles (median, 2 vs. 1) and cumulative I activity (median, 15 vs. 7 mCi) were required to cure hyperthyroidism in cohort 1 and cohort 2, respectively. Age (> 44 years), higher grade of goitre, and 2-h RAIU (> 37%) were associated with I therapy failure. The high turnover patients needed a factor of 1.5-2 times more I activity to achieve a similar cure rate compared to the normal turnover patients. The first-dose cure rate was 31% vs. 60% by propensity score analysis ( = 154), no way different (28% vs.66%) from the whole group of 312 patients.

Conclusion: High turnover Graves' disease patients, if administered standard I activity, the outcomes shall be poor. To improve the success rate, I activity should be increased by 1.5 to 2 times in the high turnover patients.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-020-00674-3.
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http://dx.doi.org/10.1007/s13139-020-00674-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881070PMC
February 2021

Head to head comparison of Ga-NGUL and Ga-PSMA-11 in patients with metastatic prostate cancer: a prospective study.

J Nucl Med 2021 Feb 26. Epub 2021 Feb 26.

Seoul National University College of Medicine, Korea, Republic of.

Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA) targeting tracer used for positron emission tomography/computed tomography (PET/CT) imaging. This study aims to compare the performance in the detection of primary and metastatic lesions, and to compare biodistribution between Ga-NGUL and Ga-PSMA-11 in the same patients with metastatic prostate cancer. Eleven patients with histologically proven, metastatic prostate cancer were prospectively recruited. Each patient underwent Ga-NGUL and Ga-PSMA-11 PET/CT within 4 days. The PET/CT scans were performed at 60 minutes after tracer injection. The quantitative tracer uptakes were obtained in normal organs including salivary glands, liver, spleen, and kidney and blood pool activity was measured in the inferior vena cava. The normal organ distribution of both tracers was quantified as SUVmean. In addition, three patients underwent dynamic PET/CT scanning (60 min) of the pelvic region to evaluate the urinary clearance. Any focal accumulation of Ga-NGUL and Ga-PSMA-11 not explained by physiologic uptake were defined as pathologic lesions. Lesion numbers and lesion uptake, as SUV, were compared. Quantitative uptakes in the kidneys, salivary glands, spleen, and liver were significantly lower on Ga-NGUL compared with Ga-PSMA-11. The blood pool activity showed no significant difference between the two tracers. The bladder time activity curve revealed a more rapid urinary clearance of Ga-NGUL. The number and sites of detected PSMA positive primary ( = 11) and metastatic lesions ( = 220) were identical between both tracers. Quantitative uptakes of primary tumors, lymph node, and bone metastases were well correlated (R2 = 0.869, 0.845, and 0.624, respectively) without significant difference ( = 0.675, 0.175, and 0.102, respectively) between Ga-NGUL and Ga-PSMA-11. Ga-NGUL showed a relatively lower tumor-to-background (gluteal muscle) ratio than Ga-PSMA-11, especially for bone metastasis. In head to head comparison with Ga-PSMA-11, Ga-NGUL showed lower uptake in normal organs and a trend of relatively low tumor-to-background ratio compared to Ga-PSMA-11. However, both tracers showed similar performance to detect PSMA avid primary and metastatic lesions without significant difference in the absolute lesion uptake. Ga-NGUL could be a valuable option for PSMA imaging and, furthermore, applied in theranostics.
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http://dx.doi.org/10.2967/jnumed.120.258434DOI Listing
February 2021

Metastatic Medulloblastoma: 18F-FDG and 68Ga-DOTANOC PET/CT in Response Evaluation.

Clin Nucl Med 2021 May;46(5):e262-e263

From the Departments of Nuclear Medicine.

Abstract: We describe the utility of molecular imaging with 18F-FDG and 68Ga-DOTANOC PET for treatment response assessment in a case of metastatic medulloblastoma. 18F-FDG and 68Ga-DOTANOC PET/CT revealed extensive metastases to bone and bone marrow. Patient subsequently had an excellent response to systemic chemotherapy which was evidenced by resolution of tracer-avid skeletal lesions on both FDG and DOTANOC PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000003435DOI Listing
May 2021

Biodistribution, pharmacokinetics, dosimetry of [Ga]Ga-DOTA.SA.FAPi, and the head-to-head comparison with [F]F-FDG PET/CT in patients with various cancers.

Eur J Nucl Med Mol Imaging 2021 Jun 26;48(6):1915-1931. Epub 2020 Nov 26.

Department of Nuclear Medicine, AIIMS, Ansari Nagar, New Delhi, PIN: 110029, India.

Purpose: [Ga]Ga-labeled fibroblast activation protein inhibitors ([Ga]Ga-FAPi) have shown promising preclinical and clinical results in PET imaging. The present study aimed to evaluate the biodistribution, pharmacokinetics, and dosimetry of [Ga]Ga-DOTA.SA.FAPi, another modified FAPi tracer, and performed a head-to-head comparison with [F]F-FDG PET/CT scans in patients with various cancers.

Methods: In this prospective study, patients underwent both [F]F-FDG and [Ga]Ga-DOTA.SA.FAPi PET/CT scans 60 min post-injection (p.i.). Dosimetry studies were conducted in three patients using [Ga]Ga-DOTA.SA.FAPi serial time-point imaging. The absorbed dose was calculated using OLINDA/EXM 2.2 software. Quantification of the uptake of the tracers was assessed using standardized uptake values corrected for lean body mass (SUL).

Results: Fifty-four patients (mean age; 48.4 years) with 14 types of cancers involving 37% breast, 24% lung, 7.4% head and neck (H&N), and remaining 31.6% patients with other histologies were evaluated prospectively. Physiological uptake of [Ga]Ga-DOTA.SA.FAPi was observed in the liver, kidneys, pancreas, heart contents, and to a lesser extent in the lacrimals, oral mucosa, salivary glands, and thyroid glands. Uptake in the target lesions on [Ga]Ga-DOTA.SA.FAPi scan was initiated at 10 min, and no additional lesions were detected in the delayed acquisition time points. The pancreas was the organ with the highest absorbed dose (5.46E-02 mSv/MBq). While the patient-based comparison between the radiotracers revealed complete concordance in the detection of primary, pleural thickening, bone and liver metastases, and second primary malignancy, discordant findings were observed in the detection of lymph node (7.5%), lung nodules (5.6%), and brain metastases (2%). According to the site of primary disease, patients with H&N cancers demonstrated the highest SULpeak and average (avg) values on [Ga]Ga-DOTA.SA-FAPi which was similar to the values of [F]F-FDG [(SULpeak: 15.4 vs. 14.2; P-0.680) (SULavg: 8.3 vs. 7.9; P-0.783)]. The lowest uptake was observed in lung cancers with both the radiotracers [(SULpeak: 5.8 vs. 7.4; P-0.238) (SULavg: 4.9 vs. 5.3; P-0.313)]. A significantly higher SULpeak and SULavg for brain metastases to normal brain parenchyma ratios were observed on [Ga]Ga-DOTA.SA.FAPi in contrast to the [F]F-FDG values {SULpeak: median: 59.3 (IQR: 33.5-130.8) versus 1.5 (1-2.3); P-0.028}. Except for brain metastases, comparable SULpeak and average values were noted between the radiotracers in all other regions of metastases with no significant difference.

Conclusion: [Ga]Ga-DOTA.SA.FAPi is a promising alternative among the FAPI class of molecules and performed well as compared to standard-of-care radiotracer [F]F-FDG in the diagnosis of various cancers.
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http://dx.doi.org/10.1007/s00259-020-05132-yDOI Listing
June 2021

Hyperplastic thyroid nodule masquerading as parathyroid adenoma in a patient with tubercular lymphadenitis induced hypercalcaemia.

BMJ Case Rep 2020 Nov 9;13(11). Epub 2020 Nov 9.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India.

Serum intact parathyroid hormone (iPTH) levels are high or high normal in patients with parathyroid adenoma. Rarely these patients can have normal or low serum iPTH values. With sandwich immunometric assays, an exceptionally high serum iPTH level can lead to falsely low measurement due to the 'hook effect'. Here, we describe the case of a 66-year-old female patient with PTH-independent hypercalcaemia which mimicked parathyroid adenoma. A multidisciplinary team approach helped in the diagnosis and management leading to complete recovery.
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http://dx.doi.org/10.1136/bcr-2020-237261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654110PMC
November 2020

[Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results.

EJNMMI Res 2020 Oct 28;10(1):130. Epub 2020 Oct 28.

Department of Nuclear Medicine, Room No: 59-A, Thyroid Clinic, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, 110029, India.

Background: [Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers.

Methods: In total, 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3-2.7 GBq) [Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR 8-14 months). The primary outcome endpoint was response assessment according to the visual analogue score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky performance status, overall survival, and safety assessment by the National Cancer Institute's Common Toxicity Criteria V5.0.

Results: In total, 40 patients (15 males and 25 females) with a mean age of 46.6 ± 15.08 years (range 24-78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal, and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty-eight patients died and the estimated median overall survival was 13 months (95% CI 10-14 months). A significant improvement was observed in the VAS, AS, and ECOG status when compared to baseline. None of the patients experienced grade III/IV haematological, kidney, or hepatotoxicity due to [Lu]Lu-DOTA-ZOL therapy.

Conclusion: [Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.
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http://dx.doi.org/10.1186/s13550-020-00709-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593375PMC
October 2020

BRAF V600E and TERT promoter mutations in paediatric and young adult papillary thyroid cancer and clinicopathological correlation.

J Pediatr Endocrinol Metab 2020 Nov;33(11):1465-1474

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Objectives The primary objective of this study was to determine the prevalence of BRAF V600E and TERTpromoter mutations in paediatric and young adult patients with papillary thyroid carcinoma (PTC) and the secondary objective, to assess their association with clinicopathological features. Methods Patients ≤20 years who underwent surgery for differentiated thyroid cancer (DTC) from 2005 to 2018 were consecutively enrolled for BRAF V600E and TERTpromoter mutations analysis and records analysed for the association of aggressive features. Univariate analysis and multivariate logistic regression were used to identify the independent predictors of BRAF V600E mutations. Results Among 100 patients with DTC, 68 patients were ≤18 years and the remaining 30 patients were >18 years of age with a median age of 17 years (IQR 14-19 years) 98 patients had PTC and 2 had FTC. BRAF V600E mutation was present in 14/98 (14.3%) PTC and TERTpromoter mutation noted in none. Multivariate analysis identified RAI refractoriness (OR:10.57, 95% CI: 2.6 to 41.6, P-0.0008) as an independent factor associated with BRAF V600E mutation. 17 patients with distant metastases were negative for both BRAF V600E or TERTpromoter mutation. No significant association was observed between age, gender, PTC variants, extra-thyroidal extension, lymphovascular invasion, multifocality, RAI administration and event rate with BRAF V600E mutation. Irrespective of BRAF V600E mutation, radioiodine refractory status (p-0.0001) had a reduced EFS probability. Conclusion In paediatric & young adult PTC, TERTpromoter mutation is absent and BRAFV600E mutation is not associated with distant metastasis. The prevalence rate of the BRAF V600E mutation is much lower compared to adult PTC patients.
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http://dx.doi.org/10.1515/jpem-2020-0174DOI Listing
November 2020

Metabolic scoring in autoimmune epilepsy-Should APE scores be modified?

Acta Neurol Scand 2021 Jan 15;143(1):13-18. Epub 2020 Oct 15.

Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India.

Objective: We evaluate the potential utility of F-18 FDG-PET in addition to MRI in the diagnostic work-up of patients with autoimmune epilepsy (AE) and propose the inclusion of functional imaging in the antibody prevalence in epilepsy (APE) scoring system.

Methods: This was a retrospective analysis in 60 patients, diagnosed and treated for AE, of whom 40 were antibody negative (presumed AE) and 20 were antibody positive (definitive AE). All patients had undergone a dedicated brain and whole body FDG-PET in the department of Nuclear Medicine.

Results: In the antibody negative group, MRI supported a diagnosis of AE in 23 patients. Both MRI and PET were indicative in 12 cases, and standalone PET was positive in 8. While MRI alone was diagnostic in 57% (23/40), the combined yield of both modalities was 77% (31/40). When PET scores were added to assign the APE score in MRI negative cases, average APE score was 5.4. In the antibody positive group, MRI supported the diagnosis of AE in 7 patients. Both MRI and PET were positive in 4 patients and standalone PET was positive in 5 patients. While MRI alone was diagnostic in 35% (7/20), the combined yield of both modalities was 60% (12/20). When PET scores were added to assign the APE score in MRI negative cases, average APE score was 6.1.

Conclusion: The inclusion of metabolic information from PET distinctly improved (the sensitivity of) APE scores to predict autoimmune origin even in antibody negative cases. A larger prospective study of similar type could justify adoption of FDG-PET into the standard diagnostic procedure.
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http://dx.doi.org/10.1111/ane.13346DOI Listing
January 2021

Efficacy and safety of Ac-PSMA-617 targeted alpha therapy in metastatic castration-resistant Prostate Cancer patients.

Theranostics 2020 23;10(20):9364-9377. Epub 2020 Jul 23.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Despite the success of several standards of care treatment options in metastatic castration-resistant prostate cancer (mCRPC), a significant number of patients attain therapeutic resistance and eventually develop disease progression. Managing these patients are currently challenging. Hence, there is an unmet need for further efficient therapeutic options that induce anti-tumor activity and improve survival. The objective of this study was to assess the safety and therapeutic efficacy of Ac-PSMA-617 targeted alpha therapy (TAT) in mCRPC patients in real-world conditions. In this prospective study, we recruited patients with mCRPC who either were refractory to Lu-PSMA-617 radioligand therapy (RLT) or did not receive previous Lu-PSMA-617 RLT. Patients were treated with Ac-PSMA-617 TAT (100 KBq/Kg body weight) at 8-weekly intervals. The primary endpoint included the assessment of biochemical response by measuring the serum prostate-specific antigen (PSA) response rate as per the prostate cancer working group criteria (PCWG3). Secondary endpoints comprised the estimation of overall survival (OS), progression-free survival (PFS), molecular tumor response assessment (PERCIST 1 criteria), disease control rate (DCR), toxicity according to CTCAE v5.0, and clinical response evaluation. A total of 28 patients were recruited for this cohort study among whom 15 (54%) received prior Lu-PSMA-617 RLT and the remaining 13 (46%) patients were Lu-PSMA-617 RLT naïve. The mean age was 69.7 years (range: 46-87 years). All patients, except one, had extensive skeletal metastases on baseline Ga-PSMA-11 PET/CT scan; one patient had lymph node dominant disease and advanced primary prostatic tumor. The mean activity administered was 26.5 ± 12 MBq (range: 9.25 - 62.9 MBq) [715.5 ± 327 µCi, range: 250 - 1700 µCi] with a median of 3 cycles (range: 1 - 7 cycles). At 8 week of post first cycle of Ac-PSMA-617 therapy (initial follow-up) and the end of the follow-up, >50% decline in PSA was observed in 25% and 39%, respectively. The median PFS and OS were 12 months (95% CI: 9 - 13 months) and 17 months (95% CI: 16 months - upper limit not reached), respectively. Molecular tumor response by PERCIST 1 criteria could be conducted in 22/28 (78.6%) patients, which revealed complete response in 2/22 (9%), partial response in 10/22 (45.4%) patients, 2/22 (9%) with stable disease, and 8/22 (36%) with progressive diseases. The disease control rate, according to the biochemical and molecular tumor response criteria, was 82% and 63.6%, respectively. Multivariate analysis revealed PSA progression as adverse prognostic indicator of OS, and any PSA decline as a good prognostic indicator of PFS. There was no Grade III/IV toxicity noted in this series. The most common side-effect was transient fatigue (50%) followed by grade I/II xerostomia (29%). Ac-PSMA-617 TAT showed promising disease control rate, even when all other therapeutic options were exhausted, with low treatment-related toxicities.
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http://dx.doi.org/10.7150/thno.48107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415797PMC
July 2020

RET gene mutation analysis and long-term clinical outcomes of medullary thyroid cancer patients.

Nucl Med Commun 2020 Nov;41(11):1136-1142

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi.

Objective: Medullary thyroid carcinoma is a rare, potentially aggressive tumour, with relatively worse prognosis than well-differentiated thyroid cancer. We evaluated the long-term outcomes and prognosis of medullary thyroid carcinoma patients at a single institution in India and compared outcomes based on results of RET protooncogene mutation analysis.

Methods: Data were retrieved through a prospectively maintained thyroid cancer database from 1998 to June 2019, and medullary thyroid carcinoma patients were recruited. RET gene mutation status (exon 10-16) was assessed. Patient with a minimum follow-up of 12 months was eligible to be part of the long-term outcome analysis.

Results: Out of 149 peripheral blood samples, 42 were positive for RET gene mutation (prevalence of 28.1%). The median follow-up duration was 48 months, ranging from 12 to 240 months. Long-term clinical outcomes of 113 patients were assessed. Two deaths were noted in this series. Both 5- and 10-year survival was cent per cent. Overall survival was 98.2% (97.3% in RET positive and 98.7% in RET negative group). Progression-free survival was 55.4% in total (60% in RET positive and 53.3% in RET negative group). No statistically significant difference was found between RET positive and RET negative groups concerning overall survival (P = 0.6011) and progression-free survival (P = 0.5140). Univariate analysis revealed high calcitonin (>10 pg/mL), stage IV disease, and presence of lymph nodal metastasis to be significant predictors of disease recurrence, however, multivariate analysis demonstrated the presence of lymph node metastases as the only significant predictor of recurrence (P = 0.0005).

Conclusions: Medullary thyroid carcinoma patients had relatively favourable long-term outcomes. Long-term survival was similar irrespective of RET mutation status. Presence of lymph node metastases appeared to be the strongest predictor of overall and progression-free survival, followed by Calcitonin level and stage of the disease.
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http://dx.doi.org/10.1097/MNM.0000000000001264DOI Listing
November 2020

Individualized dosimetry in children and young adults with differentiated thyroid cancer undergoing iodine-131 therapy.

J Pediatr Endocrinol Metab 2020 Jul 13. Epub 2020 Jul 13.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Objectives The amount of Iodine-131 to treat young patients with differentiated thyroid cancer (DTC) has not been established so far. The purpose of this study was to perform and compare blood dosimetry by "Hanscheid's approach"and lesion dosimetry by "Maxon's approach". Methods Seventy-one DTC patients ≤21 years were given diagnostic activity of 74 MBq 131I followed by whole-body scan (WBS) at 2 h (pre-void), 24 h, 48 h, and ≥72 h. Pre-therapy blood and lesion dosimetry were conducted to determine the absorbed doses to blood and lesions and to predict the therapeutic activity. The administered activities were varied from 1.11-5.55 GBq of 131I depending on disease extent. Post therapy dosimetries were again performed by acquiring WBS data at 24 h, 48 h, and ≥72 h. Results In blood dosimetry, the difference between predicted therapy activity (PTA) and actual therapeutic activity (ATA) was statistically significant in remnant and lung lesions but insignificant in nodal metastases (p=0.287). In lesion dosimetry, the difference between PTA and ATA was statistically significant for lung metastasis patients; however, not significant in remnant (p=0.163) and nodal metastases (p=0.054). The difference between predicted and observed absorbed dose was insignificant in blood dosimetry whereas, significant in lesion dosimetry. Conclusions The PTA based on 0.3 Gy recommendations of Hanscheid et al. may be adequate for patients with remnant or nodal metastases but inadequate for lung metastases. Lesion dosimetry demonstrated that there is scope to decrease the 131I empiric ATA for remnant and nodal metastases; at the same time, there is scope to increase in lung metastasis patients.
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http://dx.doi.org/10.1515/jpem-2020-0072DOI Listing
July 2020

Reply to "Fact-Checking on Lu-PSMA Nephrotoxicity".

AJR Am J Roentgenol 2020 07;215(1):W3-W4

All India Institute of Medical Sciences, New Delhi, India

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http://dx.doi.org/10.2214/AJR.20.23142DOI Listing
July 2020

177Lu-/68Ga-PSMA Theranostics in Recurrent Glioblastoma Multiforme: Proof of Concept.

Clin Nucl Med 2020 Dec;45(12):e512-e513

From the Departments of Nuclear Medicine and PET/CT.

A 37-year-old man, treated case of left temporal glioblastoma presented with headache, seizures, and progressive right-sided weakness with MRI evidence of recurrence. Exploratory Ga-PSMA PET/CT demonstrated PSMA expression in the recurrent lesion; it was decided to treat this patient with Lu-PSMA-617. After 3 cycles of Lu-PSMA-617, Ga-PSMA PET/CT showed significant reduction in PSMA uptake and regression in size of lesion on MRI with improvement in patient's symptoms and performance status. Lu-/Ga-PSMA theranostics has potential in patients with recurrent glioblastoma multiforme when other therapeutic options are not feasible.
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http://dx.doi.org/10.1097/RLU.0000000000003142DOI Listing
December 2020

Comparison of Lutetium-177 tin colloid and Rhenium-188 tin colloid radiosynovectomy in chronic knee arthritis.

Nucl Med Commun 2020 Aug;41(8):721-726

Departments of Nuclear Medicine.

Objective: To assess the role of Lutetium-177(Lu-177) tin colloid for radiosynovectomy and compare it with Rhenium-188 (Re-188) tin colloid radiosynovectomy for alleviation of pain in patients with chronic inflammatory arthritis of knee.

Methods: Patients of chronic inflammatory arthritis of the knee underwent pretherapeutic evaluation in a form of knee ultrasonogram, bone scan and clinical evaluation. Fifty-seven recruited patients were allocated at random to receive either intraarticular injections of Lu-177 tin colloid or Re-188 tin colloid. Eventually, 27 patients received Re-188 tin colloid and 30 patients received Lu-177 tin colloid. The joint was then immobilized for 2 days. Response evaluation was done using knee ultrasound, bone scan and clinical findings.

Result: Of 30, 20 patients responded to radiosynovectomy in the Lu-177 tin colloid group compared to 21/27 patients in the Re-188 tin colloid group.

Conclusion: Lu-177 tin colloid is an effective alternative to Re-188 tin colloid for radiosynovectomy in patients with chronic inflammatory knee arthritis.
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http://dx.doi.org/10.1097/MNM.0000000000001210DOI Listing
August 2020

Extrastriatal Peri-infarct Accumulation of 99mTc-TRODAT.

Clin Nucl Med 2020 Oct;45(10):e445-e446

From the Departments of Nuclear Medicine.

We describe the extrastriatal accumulation of dopamine transporter imaging agent Tc-TRODAT in the peri-infarct area in a 75-year-old man referred for dopamine transporter SPECT imaging with a suspicion of idiopathic Parkinson disease.
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http://dx.doi.org/10.1097/RLU.0000000000003017DOI Listing
October 2020

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.

Radiat Prot Dosimetry 2020 Jul;189(3):312-317

Department of Pediatric Surgery, All India Institute of Medical Sciences, 110029 New Delhi, India.

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.
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http://dx.doi.org/10.1093/rpd/ncaa044DOI Listing
July 2020

An Unusual Case of Simultaneous Cricoid and Thyroid Cartilage Metastases from Prostatic Adenocarcinoma on Ga-PSMA PET/CT.

Nucl Med Mol Imaging 2020 Feb 18;54(1):61-62. Epub 2019 Dec 18.

Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029 India.

Although prostate cancer can metastasize to any part of the body, laryngeal cartilage metastasis is extremely rare and few cases have been published so far. Here we present the case of a 65-year-old male patient, recently diagnosed with prostate adenocarcinoma, referred for staging with Ga-PSMA PET/CT. He was found to have extensive skeletal metastasis along with cartilage metastasis involving both thyroid and cricoid cartilages.
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http://dx.doi.org/10.1007/s13139-019-00625-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062982PMC
February 2020

Adrenocortical Carcinoma with Inferior Vena Cava Thrombus on F-FDG-PET-Computed Tomography.

Indian J Nucl Med 2020 Jan-Mar;35(1):87-88. Epub 2019 Dec 31.

Department of Nuclear Medicine and PET-CT, All India Institute of Medical Sciences, New Delhi, India.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm which can produce intravascular extension into the inferior vena cava (IVC) and can rarely extend into the right atrium. We describe the F Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography findings of a 57-year-old man diagnosed with ACC with IVC thrombus extending up to the right atrium.
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http://dx.doi.org/10.4103/ijnm.IJNM_107_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958943PMC
December 2019

Long-term Clinicopathological Features of a Family with Multiple Endocrine Neoplasia Type 2A Caused by C634R Gene Mutation.

Indian J Nucl Med 2020 Jan-Mar;35(1):48-53. Epub 2019 Dec 31.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Type 2 multiple endocrine neoplasia (MEN2A) is a variant of hereditary medullary thyroid carcinoma (MTC). MEN2A is characterized by the presence of the following: MTC, hyperparathyroidism, and pheochromocytoma (PHEO). The pathogenesis includes proto-oncogene mutation; the most frequently observed mutation is in exon 11 codon 634. We report pedigree of a large Indian family involving three generations including 21 members with MEN2A, in whom mutation status was determined. We then analyzed their clinical follow-up details, with a median duration of follow-up of 60 months (range: 9-276 months). Calcitonin (Ctn) levels were routinely checked during the follow-up. The index case was found to carry p.C634R mutation involving exon 11 of the gene. mutation was positive in 12 members in the family (12/21, i.e., 57%), was negative in 7 patients, and was not tested in 2 patients, as they were not available for the genetic test. Thirteen were clinically affected with MTC and 10 members had PHEO. At the last follow-up, the median Ctn level was 14.3 pg/mL (range: 2-12655 pg/mL). Four patients developed lymph nodal recurrence during follow-up, for which they underwent re-operations with median duration to recurrence being 48 months (range: 9-156 months). We highlight in this article that early diagnosis, adequate surgery, and appropriate genetic counseling with genetic screening are essential to improve the outcome of persons with MTC. Every case of MTC should be seen as familial or index case of hereditary MTC unless otherwise mutation excludes it.
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http://dx.doi.org/10.4103/ijnm.IJNM_168_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958961PMC
December 2019

Nephrocalcinosis, Renal Dysfunction, and Calculi in Patients With Primary Hypoparathyroidism on Long-Term Conventional Therapy.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.

Context: There are concerns about the long-term safety of conventional therapy on renal health in patients with hypoparathyroidism. Careful audit of these would help comparisons with upcoming parathyroid hormone therapy.

Objective: We investigated nephrocalcinosis, renal dysfunction, and calculi, their predictors and progression over long-term follow-up in patients with primary hypoparathyroidism (PH).

Design And Setting: An observational study at a tertiary care center was conducted.

Participants And Methods: A total of 165 PH patients receiving conventional therapy were evaluated by radiographs, ultrasonography, and computed tomography. Their glomerular filtration rate (GFR) was measured by Tc-99m-diethylenetriamine penta-acetic acid clearance. Clinical characteristics, serum total calcium, phosphorus, creatinine, hypercalciuria, and fractional excretion of phosphorus (FEPh) at presentation and during follow-up were analyzed as possible predictors of renal complications. Controls were 165 apparently healthy individuals.

Results: Nephrocalcinosis was present in 6.7% of PH patients but not in controls. Patients younger than 15 years at presentation and with higher serum calcium-phosphorus product were at higher risk. Nephrocalcinosis showed no significant association with cataract and intracranial calcification. Prevalence of renal calculi was comparable between hypoparathyroid patients and controls (5% vs 3.6%, P = .58). Fourteen percent of patients had a GFR less than 60 mL/min/1.73 m2. Increased FEPh during follow-up was the significant predictor of low GFR. Nephrocalcinosis developed in 9% of patients over 10 years of conventional therapy.

Conclusion: A total of 6.7% of PH patients had nephrocalcinosis, and 14% showed renal dysfunction. Prevalence of renal calculi was similar in patients and controls. Nine percent of patients developed nephrocalcinosis over 10 years of conventional therapy.
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http://dx.doi.org/10.1210/clinem/dgz319DOI Listing
April 2020

Evaluation of [Ga]Ga-DATA-TOC for imaging of neuroendocrine tumours: comparison with [Ga]Ga-DOTA-NOC PET/CT.

Eur J Nucl Med Mol Imaging 2020 04 22;47(4):860-869. Epub 2019 Nov 22.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.

Purpose: Recently, the new hybrid chelator DATA (6-amino-1,4-diazepine-triacetate) has been introduced, which has the advantage of high yield and radiolabelling of DATA-based octreotide derivative (TOC) at room temperature in contrast to tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) that needs 95 °C for effective labelling. However, the diagnostic potential of DATA-TOC has not been studied with other chelators in humans. The aim of this study was to compare the diagnostic efficacy of [Ga]Ga-DATA-TOC with [Ga]Ga-DOTA-NOC (which is the current standard for imaging neuroendocrine tumours (NET)) in patients of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Methods: Fifty patients (thirty-one males and nineteen females) with biopsy-proven GEP-NETs were included in the study. Patients age ranged from 14 to 75 years (mean 46.11 years). All patients underwent two PET studies with [Ga]Ga-DATA-TOC and [Ga]Ga-DOTA-NOC. Images were evaluated visually and semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour, mediastinum and liver. Tumour-to-liver (T/L) and tumour-to-mediastinum (T/M) SUVmax ratios were computed. For the purpose of comparison, patient-wise as well as lesion-wise analysis was carried out. The nonparametric-related samples Wilcoxon signed-rank test was used for comparison of the SUVmax values and ratios.

Results: On visual evaluation, the biodistribution and image quality of [Ga]Ga-DATA-TOC was similar to [Ga]Ga-DOTA-NOC. Physiological liver uptake was lower in [Ga]Ga-DATA-TOC as compared with [Ga]Ga-DOTA-NOC, 7.65 ± 5.37 vs 8.94 ± 5.95 (p = 0.009), respectively. On a patient-wise analysis, both [Ga]Ga-DATA-TOC and [Ga]Ga-DOTA-NOC were lesion-positive in the 44 patients (88%) and were negative in the 6 patients (12%). On a lesion-based analysis, [Ga]Ga-DATA-TOC had 98.6% concordance with [Ga]Ga-DOTA-NOC (232 out of 235 lesions detected). The target tumour SUVmax on [Ga]Ga-DATA-TOC and [Ga]Ga-DOTA-NOC were 36.63 ± 32.24 and 40.82 ± 36.89, respectively (p = 0.097). The T/L SUVmax ratios were not significantly different (5.99 ± 5.52 vs 5.67 ± 4.96, p = 0.77).

Conclusion: [Ga]Ga-DATA-TOC PET/CT imaging produced results that were comparable with [Ga]Ga-DOTA-NOC. It, thus, has potential utility as an effective and safe alternative to Ga-DOTA-NOC with the added benefit of ease, cost-effective and improved yield of instant kit-type synthesis.
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http://dx.doi.org/10.1007/s00259-019-04611-1DOI Listing
April 2020

Biomarker-Based Prediction of Progression to Dementia: F-18 FDG-PET in Amnestic MCI.

Neurol India 2019 Sep-Oct;67(5):1310-1317

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Background: Metabolic patterns on brain F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can predict the decline in amnestic mild cognitive impairment (aMCI) to Alzheimer's disease dementia (AD) or other dementias.

Objective: This study was undertaken to evaluate the diagnostic accuracy of baseline F-18 FDG-PET in aMCI for predicting conversion to AD or other dementias on follow-up.

Patients And Methods: A total of 87 patients with aMCI were enrolled in the study. Each patient underwent a detailed clinical and neuropsychological examination and FDG-PET at baseline. Each PET scan was visually classified based on predefined dementia patterns. Automated analysis of FDG PET was performed using Cortex ID (GE Healthcare). The mean follow-up duration was 30.4 ± 9.3 months (range: 18-48 months). Diagnosis of dementia at follow-up (obtained using clinical diagnostic criteria) constituted the reference standard, and all the included aMCI patients were divided into two groups: the aMCI converters (MCI-C) and MCI nonconverters (MCI-NC). Diagnostic accuracy of FDG PET was calculated using this reference standard.

Results: There were 23 MCI-C and 64 MCI-NC. Of the 23 MCI-C, 19 were diagnosed as probable AD, 1 as frontotemporal demetia (FTD), and 3 as vascular dementia (VD). Of the 64 MCI-NC, 9 had subjective improvement in cognition, and 55 remained stable. The conversion rate for all types of dementia in our series was 26.4% (23/87) and for Alzheimer's type dementia was 21.8% (19/87). The of PET-based visual interpretation was 91.9%. Sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET-based prediction of dementia conversion were 86.9% [confidence interval (CI) 66.4%-97.2%)], 93.7% (CI 84.7%-98.2%), 83.3% (CI 65.6%-92.9%), and 95.2% (CI 87.4%-98.9%), respectively. Kappa for agreement between visual and Cortex ID was 0.94 indicating excellent agreement. In the three aMCI patients progressing to VD, no specific abnormality in metabolic pattern was noted; however, there was marked cortical atrophy on computed tomography.

Conclusion: FDG-PET-based visual and cortex ID classification has a good accuracy in predicting progression to dementia including AD in the prodromal aMCI phase. Absence of typical metabolic patterns on FDG-PET can play an important exclusionary role for progression to dementia. Vascular cognitive impairment with cerebral atrophy needs further studies to confirm and uncover potential mechanisms.
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http://dx.doi.org/10.4103/0028-3886.271245DOI Listing
April 2020

Broadening horizons with Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety.

Eur J Nucl Med Mol Imaging 2020 04 10;47(4):934-946. Epub 2019 Nov 10.

Department of Nuclear Medicine, All India Institute of Medical Sciences, AIIMS, Room No. 59-A, Ansari Nagar, New Delhi, 110029, India.

Purpose: The objective of this study was to investigate and present the early results on the efficacy, safety, and quality of life of Ac-DOTATATE targeted alpha therapy (TAT) in patients with advanced, progressive, Lu-DOTATATE refractory, and somatostatin receptor (SSTR) expressing metastatic GEP-NETs.

Methods: In this prospective study, we recruited patients with metastatic GEP-NETs who were stable or progressive disease on Lu-DOTATATE therapy. Systemic TAT using Ac-DOTATATE was performed in all the patients with Ac-DOTATATE (100 kBq/kg body weight) at an interval of 8 weeks. The primary end point was to assess the objective response (measured by RECIST 1.1 and functional M.D. Anderson criteria). The secondary end points included biochemical response assessment as per the Italian Trials in Medical Oncology (ITMO), adverse event profile as per CTCAE v5.0, and clinical response assessment by the quality of life (assessed with EORTC QLQ-GI.NET21 patient-based questionnaire).

Results: Between April 2018 and March 2019, 32 patients (17 females, 15 males, mean age 52 ± 9.2 years, 35-72 years) with either stable disease after completing Lu-DOTATATE therapy (14, 44%) or progressive disease on Lu-DOTATATE therapy (18, 56%) were included in the study. The morphological response was assessed in 24/32 patients that revealed partial remission in 15 and stable disease in 9. There was no documented disease progression or deaths in the median follow-up of 8 months (range 2-13 months). There was a significant decrease in the plasma chromogranin level post-Ac-DOTATATE therapy (P < 0.0001).

Conclusion: Our short-term clinical results indicate Ac-DOTATATE TAT as a promising treatment option which adds a new dimension in patients who are refractory to Lu-DOTATATE therapy or have reached the maximum prescribed cycles of Lu-DOTATATE therapy.
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http://dx.doi.org/10.1007/s00259-019-04567-2DOI Listing
April 2020

Prospective evaluation of 68Ga-DOTANOC positron emission tomography/computed tomography and 131I-meta-iodobenzylguanidine single-photon emission computed tomography/computed tomography in extra-adrenal paragangliomas, including uncommon primary sites and to define their diagnostic roles in current scenario.

Nucl Med Commun 2019 Dec;40(12):1230-1242

Department of Nuclear Medicine.

Aim: To evaluate Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) and I-meta-iodobenzylguanidine single-photon emission computed tomography/computed tomography (131I-MIBG SPECT/CT) in patients with paragangliomas, including uncommon primaries.

Methods: Ninety patients were prospectively enrolled, and both scans were done within 2 weeks of each other. Lesions were grouped as Head/neck, abdominal, uncommon primary paraganglioma, and metastatic lesions. In most histopathology was used as reference standard.

Results: PET/CT had sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 97%, 94%, 99%,88%,97% respectively on patient wise analysis (90) and 98%, 94%, 99%, 85% and 97% respectively on lesion wise analysis (149). Comparison with MIBG SPECT/CT: Significant difference in sensitivities noted (PET/CT-98%, I-131 MIBG -39%) (P < 0.001), however, no significant difference in specificities (94% and 100%, respectively). Group-wise analysis: Head/Neck: Significant difference noted between PET/CT (sensitivity 100%) and I-131 MIBG SPECT/CT (sensitivity 22%) (P = 0.001). Abdominal: No significant difference noted in sensitivities and specificities of PET/CT and I-131 MIBG SPECT/CT. Uncommon paraganglioma: PET/CT detected 10 of 11, while I-131 MIBG detected only 2 of 11 uncommon paraganglioma. Metastatic sites: Significant difference noted between PET/CT (sensitivity 97%) and I-131 MIBG SPECT/CT (sensitivity 33%) (P < 0.0001).

Conclusion: The study demonstrates high diagnostic accuracy of Ga-DOTANOC PET/CT and superiority over I MIBG SPECT/CT for evaluation of extra-adrenal paraganglioma. The current diagnostic role of I-131 MIBG seems limited to abdominal paragangliomas and for theranostic purpose.
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http://dx.doi.org/10.1097/MNM.0000000000001096DOI Listing
December 2019

In Vivo Assessment of Tau Deposition in Alzheimer Disease and Assessing Its Relationship to Regional Brain Glucose Metabolism and Cognition.

Clin Nucl Med 2019 Nov;44(11):e597-e601

From the Departments of Nuclear Medicine.

Aim: In this study, we investigated the relationship of cerebral tau deposition (F-tau-AD-ML 104 PET/CT) with glucose metabolism (F-FDG PET/CT) and cognitive function in patients with Alzheimer disease (AD).

Patients And Methods: Seventy subjects (Mini Mental State Examination [MMSE] score <18 = 37 [AD]; MMSE score, 18-24 = 16 [early AD]) and 17 controls were included in this study. All participants underwent detailed neurological and neuropsychological evaluation, followed by F-tau-AD-ML 104 and F-FDG PET/CT imaging. Region-wise SUVmax ratios at 50 to 60 minutes postinjection were calculated for F-tau-AD-ML 104 and F-FDG, using the cerebellar cortex as the reference region. Linear models were used to investigate the association of regional F-tau-AD-ML 104 retention with F-FDG uptake and cognition (MMSE scores).

Results: F-Tau-AD-ML 104 retention was observed in the parietal lobe, temporal lobe, hippocampus, parahippocampus, frontal lobe, anterior and posterior cingulate, and precuneus in advanced and early AD patient as compared with normal controls with regional hypometabolism in overlapping regions on F-FDG PET. Significant negative association was found between F-tau-AD-ML 104 regional retention and glucose metabolism in the parietal lobe, temporal lobe, hippocampus, parahippocampus, frontal lobe, anterior and posterior cingulate, and precuneus among patients with advanced and early AD. In advanced and early AD patients, a negative association was found between F-tau-AD-ML 104 regional retention (precuneus) and cognition (MMSE score), whereas a positive association was observed between F-FDG regional uptake (precuneus) and cognition (MMSE score).

Conclusions: Tau pathology overlapped with areas of hypometabolism on FDG PET in the brains of AD patients. Tau deposition was found to have negative association with cognitive scores in these patients.
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http://dx.doi.org/10.1097/RLU.0000000000002791DOI Listing
November 2019