Publications by authors named "Parul Thakral"

15 Publications

  • Page 1 of 1

Upfront Use of 177Lu-Labeled PSMA Radioligand Therapy and Treatment Response Assessment in Treatment-Naive Prostate Cancer.

Clin Nucl Med 2021 Sep 13. Epub 2021 Sep 13.

From the Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Abstract: Prostatic malignancy is the most common type of nonskin cancer and associated with significant morbidity and mortality. Early androgen deprivation therapy (ADT) is the treatment of choice in metastatic prostate cancer, whereas ADT delays progression of disease, but it is associated with significant adverse effects and frequently impairs the quality of life. Therefore, there is growing interest in treatments to postpone ADT while achieving a good progression-free survival. We present a case of oligometastatic prostate cancer, who was treated upfront with 177Lu-labeled PSMA radioligand therapy and demonstrated excellent response to a single dose of 177Lu-PSMA-617.
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http://dx.doi.org/10.1097/RLU.0000000000003890DOI Listing
September 2021

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma.

Indian J Nucl Med 2021 Apr-Jun;36(2):114-119. Epub 2021 Jun 21.

Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Purpose: Ac-225 labeled with prostate-specific membrane antigen (PSMA-617), a transmembrane glycoprotein which is highly expressed in prostate carcinoma cells, is presently being considered a promising agent of targeted alpha therapy for the treatment of patients suffering from metastatic castration-resistant prostate cancer. In the present study, we report an optimized protocol for the preparation of therapeutic dose of Ac-225 PSMA-617 with high yield and radiochemical purity (RCP).

Methods: Ac-225 PSMA-617 was prepared by adding the peptidic precursor-PSMA-617 (molar ratios, Ac-225: PSMA-617 = 30:1) in 1 ml ascorbate buffer to Ac-225 and heating the reaction mixture at 90°C for 25 min to obtain the radiopeptide with high RCP and yield. The radiolabeled peptide was administered in patients who met the eligibility criteria and posttherapy assessment was done.

Results: Ten batches of Ac-225 PSMA-617 were prepared following this protocol. The radiopeptide was obtained with an adequate yield of 85%-87% and RCP of 97%-99%.

Conclusion: The current protocol allows single-step, successful, routine inhouse radiolabeling of Ac-225 with PSMA-617 with high yield and RCP.
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http://dx.doi.org/10.4103/ijnm.ijnm_200_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320836PMC
June 2021

Dosimetric analyses of intra-arterial versus standard intravenous administration of 177Lu-DOTATATE in patients of well differentiated neuroendocrine tumor with liver-dominant metastatic disease.

Br J Radiol 2021 Aug 6:20210403. Epub 2021 Aug 6.

Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, India.

Objective: The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of Lu-DOTATATE.

Methods: 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software.

Results: The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly ( < 0.05) but differed insignificantly in spleen and kidneys ( > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2-251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12-55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group.

Conclusion: IA administration of Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT.

Advances In Knowledge: Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.
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http://dx.doi.org/10.1259/bjr.20210403DOI Listing
August 2021

Invasive Fungal Infection in COVID-19-Recovered Patient Detected on 18F-FDG-Labeled Leukocytes PET/CT Scan.

Clin Nucl Med 2021 Jul 26. Epub 2021 Jul 26.

From the Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Abstract: Occurrence of invasive fungal infections has gained significant attention during recent times in patients with COVID-19. Patients with severe form of COVID-19, such as those treated in the intensive care unit with prolonged steroid use, are particularly vulnerable to secondary bacterial and fungal infections. Disseminated systemic mycosis is a life-threatening condition, especially in immunocompromised patients. Here, we report a case of a recovered severe COVID-19 patient, who presented with persistent fever. 18F-FDG-labeled leukocyte scan revealed focal accumulation of radiotracer in the small intestine and right lung lower lobe. Subsequently, performed biopsy revealed mucormycosis.
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http://dx.doi.org/10.1097/RLU.0000000000003852DOI Listing
July 2021

Therapeutic efficacy of Ac-PSMA-617 targeted alpha therapy in patients of metastatic castrate resistant prostate cancer after taxane-based chemotherapy.

Ann Nucl Med 2021 Jul 31;35(7):794-810. Epub 2021 May 31.

Department of Medical Oncology, Fortis Memorial Research Institute, Gurugram, Haryana, India.

Objectives: Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience of targeted alpha therapy with Ac-PSMA-617 in mCRPC patients who have failed therapy with taxanes.

Materials And Methods: Thirty-eight patients with CRPC with progressive disease following at least one taxane-based chemotherapy received Ac-PSMA-617 between July 2017 and Nov 2019. Primary end point was a composite 50% PSA and radiological response. Secondary endpoints were PFS, OS, and changes in QOL. The differences in outcomes between patients with skeletal and lymph-node metastases versus those with visceral metastases were also studied.

Results: A composite response by predetermined criteria was observed in 25 (66%) of 38 patients. The median PFS was 8 months (95% CI 5.3-10.6 months). Median overall survival was 12 months (95% CI 9.1-14.9) with 16 patients alive at the time of censorship. There was no difference in response rates or survival statistics between patients with visceral metastases versus those with only bone and lymph-node metastases (Chi-square 1.51, df 1, Sig 0.218). The most common adverse effect was xerostomia. On the QOL Symptom score, Pain, Fatigue Insomnia, and constipation showed a significant improvement as compared to baseline.

Conclusions: Ac-PSMA-617 is a safe and tolerable treatment option for mCRPC that demonstrates marked anti-tumour activity with improvement in quality of life even in patients of metastatic CRPC who have been previously treated with taxane-based chemotherapy.
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http://dx.doi.org/10.1007/s12149-021-01617-4DOI Listing
July 2021

Incremental Value of Ga-68 Prostate-Specific Membrane Antigen-11 Positron-Emission Tomography/Computed Tomography Scan for Preoperative Risk Stratification of Prostate Cancer.

Indian J Nucl Med 2020 Apr-Jun;35(2):93-99. Epub 2020 Mar 12.

Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Background: Prostate cancer (PC) is the second-most common cause of cancer.Ga-prostate-specific membrane antigen (PSMA)-11 positron-emission tomography/computed tomography (PET/CT) scan help in accurate staging of PC owing to its high PSMA avidity and specificity. The aim of this prospective observational study was to determine the incremental value of Ga-68 PSMA-11 PET/CT over multiparametric magnetic resonance imaging (mpMRI) in the locoregional staging of intermediate- and high-risk PC using histopathology from radical prostatectomy specimens as a gold standard.

Materials And Methods: This was a prospective study, including 35 patients with biopsy-proven prostate carcinoma. All the patients underwent whole-body Ga-68 PSMA-11 PET/CT scans along with mpMRI including a dedicated pelvic imaging protocol within a time window of ± 10 days. The reference standard was based on histopathological results, postprostatectomy.

Results: All 35 patients showed Ga-68 PSMA-11-avid disease, of which 29 underwent radical prostatectomy, one underwent radiation therapy, and five did not undergo surgery owing to metastases. A total of 52 PC lesions were detected in 29 patients on histopathology. Of 52 lesions, 29 lesions were identified in prostate parenchyma and 23 were extraprostatic lesions on histopathology. Ga-68 PSMA-11 PET/CT detected a total of 45 lesions, of which 29 lesions were located within the prostate parenchyma and 16 were representative of extraprostatic lesions. mpMRI detected a total of 36 lesions, of which 29 lesions were located within the prostate parenchyma and seven were representative of extraprostatic lesions. The overall sensitivity of Ga-PSMA PET/CT and mpMRI in the detection of lesions was 86.2% and 68.6%, respectively. However, the overall specificity was 94.7% and 89.1% for Ga-PSMA and mpMRI, respectively.

Conclusion: Ga-68 PSMA-11 PET/CT provided superior locoregional preoperative staging of PC as compared to mpMRI in intermediate- and high-risk PC patients.
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http://dx.doi.org/10.4103/ijnm.IJNM_189_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182336PMC
March 2020

Radiation Exposure to the Nuclear Medicine Personnel During Preparation and Handling of Bi-Radiopharmaceuticals.

J Nucl Med Technol 2020 Mar 11;48(1):68-72. Epub 2019 Oct 11.

Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, India.

Because of the excellent ability of α-particles to transfer a high amount of energy over a short tissue range, targeted α-therapy has been attracting rising numbers of nuclear medicine centers. In this study, we estimated the radiation exposure to the occupational workers with pocket dosimeters during handling of the α-emitter Bi, used for targeted α-therapy of neuroendocrine tumor and castration-resistant prostate cancer patients. The dose rates from patients at different distances and time points after injection of the therapy were also evaluated. This prospective study was done in the Department of Nuclear Medicine at Fortis Memorial Research Institute, Gurgaon, India. Twelve patients with neuroendocrine tumors or castration-resistant prostate cancer were enrolled to receive Bi-DOTATOC or Bi-prostate-specific membrane antigen therapy, respectively. Each patient received 2-3 intravenous injections of Bi-peptide, 266-362 MBq (7.2-9.8 mCi) in a single cycle over 2-3 d. The radiation exposure to nuclear medicine personnel at the chest and extremity levels was assessed for tasks such as elution, dispensing, injecting, and collecting blood samples. Radiation levels were measured at distances of 1 cm and 1 m from patients immediately after, and at 1, 2, and 4 h after, the administration of Bi-peptide. The external dose incurred at the chest level by radiopharmacists during synthesis, by physicians during injection, by technologists during imaging, and by nurses during sample collection was 2-7 μSv/procedure. The extremity dose was 1-14 μSv/procedure. The dose rate at 1 m from patients immediately after Bi-radiopharmaceutical injection was 0.02-0.03 μSv/MBq⋅h. The external radiation doses received by occupational workers involved in various procedures were far below the limit prescribed by the regulatory authority (20 mSv/y).
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http://dx.doi.org/10.2967/jnmt.119.230516DOI Listing
March 2020

Molecular Imaging to the Surgeons Rescue: Gallium-68 DOTA-Exendin-4 Positron Emission Tomography-Computed Tomography in Pre-operative Localization of Insulinomas.

Indian J Nucl Med 2019 Jan-Mar;34(1):14-18

Department of Paediatric Oncology, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Background: Insulinoma is an islet-cell neoplasm that secretes insulin. It is usually localized to the pancreas and is often the most common cause of endogenous hyperinsulinemic hypoglycaemia in non-diabetic adult patients. Surgical excision with a curative intent is the standard modality of treatment, and it requires precise localization of tumor tissue. Ga-68 DOTA-exendin-4 PET/CT scan is a clinically reasonable and sensitive scan for the identification of insulinoma. The aim of this prospective cohort study was to determine the overall accuracy of Ga-68 DOTA-exendin-4 PET/CT scan in the detection of insulinoma.

Materials And Methods: Eight patients with fasting hyperinsulinemic hypoglycaemia with neuroglycopenic symptoms were enrolled in this study which was conducted during October 2016 to October 2017. Whole body PET/CT scan was performed on a Philips time of flight PET/CT scanner, 60 minutes after injection of Ga-68 DOTA-exendin-4 (and also Ga-68 DOTANOC). The imaging findings were compared to the histopathological diagnosis in six out of eight patients and to subsequent follow up in the remaining two patients who did not undergo surgery.

Results: The sensitivity of Ga-68 DOTA-Exendin-4 PET/CT scan in insulinoma detection was found to be 75%.

Conclusion: Ga-68 DOTA-Exendin-4 PET/CT scan is highly sensitive for identification and exact localization of insulinoma which can guide better surgical exploration. However, randomised controlled trials are needed to assess the accuracy of Ga-68 DOTA-Exendin PET/CT scan in localization of insulinoma.
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http://dx.doi.org/10.4103/ijnm.IJNM_119_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352648PMC
February 2019

Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/temozolomide (CAP/TEM).

Br J Radiol 2018 Nov 27;91(1091):20170172. Epub 2018 Jul 27.

1 Department of Nuclear Medicine, Fortis Memorial Research Institute , Gurgaon , India.

Objective:: Two radiosensitizing chemotherapeutic drugs, capecitabine (CAP) and temozolomide (TEM), are administered concurrently to enhance the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT). This study aims to assess the biodistribution and normal-organ and tumor radiation dosimetry for Lu-177 DOTATATE administered concurrently with CAP/TEM.

Methods:: 20 patients with non-resectable histologically confirmed gastroenteropancreatic neuroendocrine tumors with normal kidney function, a normal haematological profile and somatostatin receptor expression of the tumor lesions, as scintigraphically assessed by a Ga-68 DOTANOC scan, were included in two groups-case group (n = 10) and control group (n = 10). Patients included in case group were those who were advised concomitant CAPTEM therapy by the treating medical oncologist. Patients were administered CAP orally at a dose of 600mg m bovine serum albumin twice a day for 14 days starting 9 days prior to PRRT and oral TEM as a single dose at a dose of 75 mg m was given concurrently for the last 5 days commencing on the day of PRRT (days 9-14). In the control group, patients were treated with Lu-177 DOTATATE only. For PRRT, 6.4 GBq-7.6 GBq (173-207 mCi) of Lu-177 DOTATATE was administered as infusion into each patient over 10-15 min in a solution with positively charged amino acids for renal protection. Dosimetric calculations were done using the HERMES software.

Results:: Physiological uptake of Lu-177 DOTATATE was seen in all patients in liver, spleen kidneys, and bone marrow. Radiation absorbed doses (mean ± standard deviation) were obtained as 0.29 ± 0.12 mGy/MBq for kidneys, 0.30 ± 0.18 mGy/MBq for liver, 0.63 ± 0.37 mGy/MBq for spleen, 0.019 ± 0.001 mGy/MBq for bone marrow and 3.85 ± 1.74 mGy/MBq for tumours in the case group and they were 0.31± 0.26, 0.24 ± 0.14, 0.64 ± 0.42, 0.017 ± 0.016, 5.6 ± 11.27 mGy/MBq in kidneys, liver, spleen, bone marrow and neuroendocrine tumour, respectively, in the control group. Mann-Whitney U test between the variables of two groups showed an insignificant difference (p > 0.05).

Conclusions:: The authors demonstrated no significant difference between the tumor and organ doses with Lu-177 DOTATATE in the patients treated with and without concomitant chemotherapy.

Advances In Knowledge:: To our knowledge, this is the first dedicated study exhibiting dosimetric analysis in patients undergoing PRRT in combination with chemotherapy.
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http://dx.doi.org/10.1259/bjr.20170172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475937PMC
November 2018

Radiation Dose to the Occupational Worker during the Synthesis of Re-labeled Radiopharmaceuticals in the Nuclear Medicine Department.

Indian J Nucl Med 2018 Jan-Mar;33(1):1-5

Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

Aim: The aim of this study is to estimate whole-body radiation dose to the radiopharmacist involved in labeling of three different Re-labeled compounds, namely, Re-Lipiodol, Re-tin colloid, and Re-hydroxyl-ethylidene-diphosphonate (HEDP) and to compare the occupational burden with the dose limits recommended by Atomic Energy Regulatory Board, India.

Materials And Methods: The Department of Nuclear Medicine at Fortis Memorial Research Institute currently synthesizes three different Rhenium-188 labeled compounds, namely, Re-Lipiodol, Re-HEDP, and Re-tin colloid. To estimate the radiation exposure to the radiopharmacist involved in the synthesis, a survey meter was used to measure radiation level before the start of labeling procedure in the radiopharmacy by keeping it at the location where the radiopharmacist normally stands during preparation. Data were collected for 6 syntheses of each Re-Lipiodol, 4 for Re-HEDP, and 3 for Re-tin colloid followed by the quality control. The pocket dosimeter was used by the radiopharmacistat chest level, performing the labeling of Re-labeled compounds. All radiopharmaceuticals were synthesized by a single radiopharmacist.

Results: 1850 MBq (50 mCi) W-Re generator was eluted before the preparation of each radiopharmaceutical. The amount of ReO4 used for labeling with lipiodol/4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol, HEDP, and Tin colloid was in the range of 3182-4440 MBq (86-120 mCi), 2812-3774 MBq (76-102 mCi), and 962-1295 MBq (26-35 mCi), respectively. Meantime required to complete the synthesis was 95, 40, and 131.5 min, respectively. Mean whole-body effective dose received was 0.052, 0.009, and 0.004 mSv, respectively, as measured by using the pocket dosimeter.

Conclusion: From this small study, we observed that the whole-body radiation dose to the radiopharmacist in radiolabeling and quality control of Re-labeled radiopharmaceuticals is within prescribed limits at the current synthesis frequency.
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http://dx.doi.org/10.4103/ijnm.IJNM_133_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798090PMC
February 2018

Rare Sites of Metastases in Prostate Cancer Detected on Ga-68 PSMA PET/CT Scan-A Case Series.

Indian J Nucl Med 2017 Jan-Mar;32(1):13-15

Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, India.

Ga-68 labeled prostate-specific membrane antigen (PSMA) whole body PET/CT scan is a novel upcoming modality for the evaluation of prostate cancer. We present three cases of prostate cancer showing rare sites of metastases like brain, penis, and liver detected on Ga-68 PSMA PET/CT scan thus emphasizing its role in lesion detection and staging.
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http://dx.doi.org/10.4103/0972-3919.198450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317062PMC
March 2017

Preliminary Experience with Yttrium-90-labelled Rituximab (Chimeric Anti CD-20 Antibody) in Patients with Relapsed and Refractory B Cell Non-Hodgkins Lymphoma.

Curr Radiopharm 2016 ;9(2):160-8

Room No-57A, Department of Nuclear Medicine, AIIMS, Ansari Nagar, New Delhi, India.

Background And Objectives: The aim of the study is to evaluate the therapeutic efficacy and safety of Yttrium- 90 radiolabelled chimeric anti CD20 antibody-Rituximab in the treatment of patients with relapsed/ refractory B cell Non-Hodgkins Lymphoma (NHL).

Methods: Twenty patients with relapsed/refractory CD20+ NHL in progressive state were included in the study. These patients had undergone a median of 2 (range 2-5) prior standard chemotherapy ± immunotherapy regimens. All the patients received rituximab 250 mg/m2 on days 1 and 8, and either 14 MBq/kg (0.4 mCi/kg) or 11 MBq/kg (0.3 mCi/kg) of Y-90 Rituximab on day 8 (maximum dose, 32 mCi) depending upon their platelet count. The patients were observed for systemic toxicity and response for at least 12 weeks after therapy.

Results: No acute adverse effects were observed after the administration of 90Y-Rituximab. Overall response rate (ORR) was 45% of which complete response (CR) was observed in 2 patients, stable disease in 1 patient and partial response in 6 patients. The therapy was well tolerated with grade IV thrombocytopenia, neutropenia and anemia observed in 3, 4 and 2 patients respectively.

Conclusion: 90Y-Rituximab therapy is safe and well tolerated in high risk extensively pretreated NHL patients. Toxicity is primarily hematologic, transient and reversible.
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http://dx.doi.org/10.2174/1874471009999160625110400DOI Listing
February 2017

Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

Nucl Med Commun 2016 Jul;37(7):735-42

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

Objective: Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab.

Materials And Methods: Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software.

Results: The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively.

Conclusion: There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.
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http://dx.doi.org/10.1097/MNM.0000000000000501DOI Listing
July 2016

An approach for conjugation of (177) Lu- DOTA-SCN- Rituximab (BioSim) & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients.

Indian J Med Res 2014 Apr;139(4):544-54

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

Background & Objectives: The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures.

Methods: Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177 Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed.

Results: An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim).The radiochemical purity of the labelled antibody was > 95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC.

Interpretation & Conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma can be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078492PMC
April 2014

Dosimetric analyses of kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors of patients treated with 177Lu-DOTATATE.

Clin Nucl Med 2013 Mar;38(3):188-94

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

Objectives: The aim of this work was to calculate the radiation absorbed dose to kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors (NETs) of patients treated with (177)Lu-DOTATATE.

Methods: We enrolled 61 patients (male/female patients, 40/21) with mean age of 48.1 ± 15.3 years affected by different types of NETs diagnosed with (68)Ga-DOTANOC PET-CT and biochemical markers. For radiation protection of kidneys, amino acid mixture (lysine and arginine) was coinfused; 3.7 to 7.4 GBq (100-200 mCi) of (177)Lu-DOTATATE was infused to each patient over 30 minutes. Each patient underwent a series of 9 whole-body scans at 30 minutes (prevoid) and 4, 8, 12, 24, 48, 96, 144, and 168 h. The organs included in dosimetric calculation were kidney, liver, spleen, pituitary gland, and NETs. All dosimetric calculations were done using the OLINDA/EXM 1.0 software.

Results: Physiological uptake of (177)Lu-DOTATATE was seen in all patients in kidneys, liver, spleen, and pituitary gland. Radiation absorbed doses were calculated: 0.57 ± 0.09 mGy/MBq for kidneys, 0.27 ± 0.05 mGy/MBq for liver, 1.17 ± 0.14 mGy/MBq for spleen, 0.058 ± 0.011 mGy/MBq for pituitary gland, and 3.41 ± 0.68 mGy/MBq for NETs.

Conclusions: The maximum cumulative activity of (177)Lu-DOTATATE that can be safely administered to a patient within permissible renal threshold in our study was found to be 40 GBq (1100 mCi). However, there are considerable interpatient differences in absorbed doses of all organs requiring individualized dosimetry for optimizing tumor dose.
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http://dx.doi.org/10.1097/RLU.0b013e3182814ac1DOI Listing
March 2013
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