On the Optimization of the Protocol for Automated Radiosyntheses of [Ga]Ga-Pentixafor, [Ga]Ga-FAPI-4 and [Ga]Ga-DOTATATE in a Modular-Lab Standard.

Objectives: The present work describes the automated radiochemical synthesis of different PET tracers like [Ga]Ga-Pentixafor, [Ga]Ga-FAPI-4 and [Ga]Ga-DOTATATE using optimized single protocol in the non-cassette based Eckert & Ziegler (EZ) Modular Lab (fixed tubing system) without any modification in the inbuilt human machine interface (HMI) software. Recently, PET agents viz. [Ga]Ga-Pentixafor and [Ga]Ga-FAPI-4 are gaining prominence for the diagnosis of overexpressed Chemokine Receptor-4 (CXCR4) and Fibroblast Activation Protein (FAP) receptor, respectively, in the microenvironment of numerous cancer types.

Clinical Internal Dosimetry and Biodistribution of 177 Lu-DOTA-Trastuzumab in HER2-Positive Metastatic and Locally Advanced Breast Carcinoma.

Objective: The aim of this study was to assess the biodistribution and dosimetry of 177 Lu-DOTA-trastuzumab in patients with HER2-positive breast carcinoma using whole-body (WB) planar imaging at multiple time points.

Patients And Methods: This study was a prospective evaluation of HER2-positive metastatic/locally advanced breast carcinoma patients who underwent gamma camera imaging for dosimetry and biodistribution studies by using 177 Lu-DOTA-trastuzumab. The standard diagnostic dosimetry protocol was followed, which included cold trastuzumab injection followed by in-house produced 177 Lu-DOTA-trastuzumab.

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

The development of humanized monoclonal antibodies (MAbs) with Lutetium-177 ([Lu]Lu) has brought a paradigm shift in the arena of targeted therapy of various cancers. [Lu]Lu-DOTA-Rituximab and [Lu]Lu-DOTA-Trastuzumab have gained prominence due to their improved therapeutic efficacy in the treatment of lymphoma and breast cancer. The clinical dose formulation of these radiolabeled MAbs, using low specific activity [Lu]LuCl, requires extensive optimization of the radiolabeling protocol.

Evaluation of Different Methods for the Detection of Anti- Thyroglobulin Autoantibody: Prevalence of Anti-Thyroglobulin Autoantibody and Anti-Microsomal Autoantibody in Thyroid Cancer Patients.

Four anti-thyroglobulin autoantibodies (TgAb) assays were evaluated for their reference interval, method agreement, concordance etc. Prevalence of TgAb and anti-thyroid peroxidase was studied in differentiated thyroid cancer (DTC) and control. Reference intervals for TgAb assays varied from method to method due to varied assay designs.

Clinical Dose Preparation of [Lu]Lu-DOTA-Pertuzumab Using Medium Specific Activity [Lu]LuCl for Radioimmunotherapy of Breast and Epithelial Ovarian Cancers, with HER2 Receptor Overexpression.

The overexpression of human epidermal growth factor receptor 2 (HER2) is commonly associated with metastatic breast cancer and epithelial ovarian cancer. The U.S.

Automated radiochemical synthesis of pharmaceutical grade [ F]FLT using 3-N-Boc-5'-O-dimethoxytrityl-3'-O-nosyl-thymidine precursor and its Sep-Pak® purification employing selective elution from reversed phase.

Pharmaceutical grade 3'-deoxy-3'-[ F]fluorothymidine [ F]FLT was synthesized using 3-N-Boc-5'-O-dimethoxytrityl-3'-O-nosyl-thymidine (BOC-Nosyl) precursor, in the general purpose TRACERlab FX modules. Purification of [ F]FLT, via solid phase extraction (SPE) after radiosynthesis, using a combination of different SPE cartridges, yielded satisfactory results, with radiochemical and chemical purity >99%. While the non-decay corrected radiochemical yield (RCY) with 20 mg (24 μmole) of BOC-Nosyl precursor was found to be 6.

Estimation of Absorbed Doses of Indigenously Produced "Direct-route" Lutetium-177-[Lu]Lu-DOTA-TATE PRRT in Normal Organs and Tumor Lesions in Patients of Metastatic Neuroendocrine Tumors: Comparison with No-Carrier-Added [Lu]Lu-DOTA-TATE and the Trend with Multiple Cycles.

Lutetium-177-labeled somatostatin analogue, [Lu]Lu-DOTA-TATE is most commonly used across the world for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs). The primary objective of this study was to estimate the absorbed doses in organs and tumor lesions in NET patients treated with indigenously produced "direct-route" [Lu]Lu-labeled DOTA-TATE and impact of multiple treatment cycles on absorbed doses, and compare with those treated with no-carrier-added [Lu]Lu-labeled DOTA-TATE. Sixty patients of NET were enrolled in this prospective study.

Prospective evaluation of organ-specific dose and lesional doses following therapeutic [177Lu]Lu-EDTMP administration in patients with multiple skeletal metastases and its correlation with clinical hematological toxicity.

Aim: In patients with multiple skeletal metastases, accurate estimation of absorbed doses to radiosensitive bone marrow in bone-directed systemic radionuclide therapies (RNT) is critically important from clinical dose determination standpoint. The primary aim of the present study was to estimate the radiation absorbed doses of therapeutic [177Lu]Lu-EDTMP to bone marrow by two methods viz. Medical Internal Radiation Dose (MIRD) schema and using OLINDA software and correlate with hematological toxicity.

Therapeutic Multidose Preparation of a Ready-to-Use Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy.

[Lu]Lu-prostate-specific membrane antigen (PSMA)-617 has emerged as a promising radiopharmaceutical for targeting PSMA in metastatic castrate-resistant prostate carcinoma (mCRPC). We have optimized the radiolabeling protocol for a multidose formulation (27-28.8 GBq equivalent to 6-7 patient-doses) of [Lu]Lu-PSMA-617 using [Lu]Lu produced via Lu(n,γ)Lu route with moderate specific activity (0.

Initial clinical evaluation of indigenous Y-DOTATATE in sequential duo-PRRT approach (Lu-DOTATATE and Y-DOTATATE) in neuroendocrine tumors with large bulky disease: Observation on tolerability, Y-DOTATATE post- PRRT imaging characteristics (bremsstrahlung and PETCT) and early adverse effects.

Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) alone has lesser potential in the clinical setting of neuroendocrine tumor (NET) with large bulky disease and nonhomogeneous somatostatin receptors (SSTR) distribution, owing to lower energy (Eβmax 0.497 MeV) and a shorter particle penetration range (maximum 2-4 mm) of Lu. In large bulky NETs, Yttrium (Y) has the theoretical advantages because of a longer beta particle penetration range (a maximum soft tissue penetration of 11 mm).

On the Separation of Yttrium-90 from High-Level Liquid Waste: Purification to Clinical-Grade Radiochemical Precursor, Clinical Translation in Formulation of Y-DOTATATE Patient Dose.

The quality control parameters of in-house-produced Y-Acetate from high-level liquid waste (HLLW) using supported liquid membrane (SLM) technology were validated and compared with the pharmacopeia standard. The radiolabeling of DOTATATE yielding Y-DOTATATE in acceptable radiochemical purity (RCP), with expected pharmacological behavior in models, establish the quality of Y-Acetate. Clinical translation of Y-Acetate in formulation of Y-DOTATATE adds support toward its use as clinical-grade radiochemical.

Production, characterization and in-vitro applications of single-domain antibody against thyroglobulin selected from novel T7 phage display library.

Single- domain antibodies (SdAbs) have been deployed in various biomedical applications in the recent past. However, there are no reports of their use in the immunoradiometric assays (IRMA) for thyroglobulin (Tg). Tg is the precursor molecule for the biosynthesis of thyroid hormones: thyroxine and triiodothyronine, which are essential for the regulation of normal metabolism in all vertebrates.

One decade of 'Bench-to-Bedside' peptide receptor radionuclide therapy with indigenous [Lu]Lu-DOTATATE obtained through 'Direct' neutron activation route: lessons learnt including practice evolution in an Indian setting.

The present treatise chronicles one decade of experience pertaining to clinical PRRT services in a large-volume tertiary cancer care centre in India delivering over 4,000 therapies, an exemplar of successful PRRT programme employing indigenous Lutetium production and resources. For the purpose of systematic discussion, we have sub-divided the communication into 3 specific parts: (a) Radiopharmaceutical aspects that describes Lutetium production through 'Direct' Neutron Activation Route and the subsequent radiolabeling procedures, (b) The specific clinical nuances and finer learning points (apart from the routine standard procedure) based upon clinical experience and how it has undergone practice evolution in our setting and (c) Dosimetry results with this indigenous product and radiation safety/health physics aspects involved in PRRT services. Initiated in 2010 at our centre, the PRRT programme is a perfect example of affordable quality health care delivery, with indigenous production of the radionuclide (Lu) in the reactor and subsequent radiolabeling of the radiopharmaceutical ([Lu]Lu-DOTATATE) at the hospital radiopharmacy unit of the centre, which enabled catering to the needs of a large number of patients of progressive, metastatic and advanced Neuroendocrine Neoplasms (NENs) and related malignancies.

Clinical Efficacy of Sodium [99mTc] Pertechnetate from Low Specific Activity 99Mo/99mTc Autosolex Generator in Hospital Radiopharmacy Centre.

Background: Few nuclear reactors in the world producing high specific activity (HSA) 99Mo using enriched 235U (HEU), are aging and are planned for shut down in the near future. Further, HEU will not be freely available, due to safeguards, and the technology for 99Mo from low-enriched 235U (LEU) is not yet widely accepted since 239Pu contamination in the product is an issue. Production of 99mTc from low specific activity (LSA) 99Mo obtained from 98Mo(n,)99Mo reaction in research reactor and 100Mo(,n)99Mo reaction in accelerator or directly from 100Mo(p,2n)99mTc nuclear reaction in cyclotron, has been explored [1].

Surface modified silk fibroin nanoparticles for improved delivery of doxorubicin: Development, characterization, in-vitro studies.

Silk fibroin nanoparticles possess the hydrophobic nature which assists them to become a good substrate for reticulo-endothelial system (RES) and macrophageal uptake. Surface coating of these nanoparticles with hydrophilic stabilizers, like Tween-80 make them long circulating and facilitate their uptake by low density lipoprotein (LDL) receptors to cross blood brain barrier (BBB). Surface modified silk fibroin nanoparticles bearing anti-cancer agent doxorubicin (DOX) were fabricated by desolvation method and coated with Tween-80 as surface modifier.

Sequential Duo-Peptide Receptor Radionuclide Therapy With Indigenous 90Y-DOTATATE and 177Lu-DOTATATE in Large-Volume Neuroendocrine Tumors: Posttherapy Bremsstrahlung and PET/CT Imaging Following 90Y-DOTATATE Treatment.

The efficacy of Lu-DOTATATE in large neuroendocrine tumors (NETs) is reduced because of the lower energy (Eβmax 0.497 MeV) and shorter range of Lu. The pure β-emitter Y with its longer β range is more effective in larger tumors.

Examining Absorbed Doses of Indigenously Developed Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy.

The objective of this study was to estimate the absorbed doses to the normal organs and tumor lesions in metastatic castration-resistant prostate cancer (mCRPC) patients treated with indigenously developed Lu-PSMA-617 that could establish optimal treatment protocol with minimum risk to the dose-limiting organs. Furthermore, attempt was also made to compare radiation absorbed doses for normal organs and tumor lesions in subsequent cycles of Lu-PSMA-617 peptide receptor radioligand therapy (PRLT) in the same group of patients during the course of treatment. A total of 30 patients of proven mCRPC were enrolled for this prospective study.

Clinical utility of Lu-DOTATATE PRRT in somatostatin receptor-positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity.

Background: The primary aim of this study was to evaluate the therapeutic efficacy and outcome of Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor-positive metastatic medullary thyroid carcinoma (MTC), including progression-free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients.

Methods: A total of 43 somatostatin receptor-positive metastatic MTC patients, treated with Lu-DOTATATE PRRT in a large tertiary care center, were included in this analysis.

Comparison of Serum Thyroglobulin Levels in Differentiated Thyroid Cancer Patients Using In-House Developed Radioimmunoassay and Immunoradiometric Procedures.

Thyroglobulin (Tg) is a proven tumor marker in the follow-up and post-operative management of patients with differentiated thyroid cancer (DTC). All assays for serum thyroglobulin (s-Tg) are based on immunoassays, however, the assay technique has a bearing on the variations seen in the estimations. We studied this using four in-house developed radioimmunoassays (RIA) and immunoradiometric assays (IRMA).

Therapeutic efficacy, prognostic variables and clinical outcome of Lu-PSMA-617 PRLT in progressive mCRPC following multiple lines of treatment: prognostic implications of high FDG uptake on dual tracer PET-CT vis-à-vis Gleason score in such cohort.

Objective: To evaluate the therapeutic response, progression free survival (PFS), overall survival (OS) and clinical toxicity of Lu-PSMA-617 PSMA targeted radioligand therapy (PRLT) in the setting of heavily pre-treated metastatic castrate-resistant prostate cancer (mCPRC) patients and also examine the association of prognostic variables with therapeutic outcome in such patient cohort.

Methods: We examined the medical records of mCRPC patients who had undergone Lu-PSMA-617 PRLT from March 2017 to February 2019 in our institute. Patients receiving equal to or more than two cycles were included and analyzed in this retroprospective study.

Differential Uptake of 68Ga-PSMA-HBED-CC (PSMA-11) in Low-Grade Versus High-Grade Gliomas in Treatment-Naive Patients.

Purpose Of The Report: Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein, which is not only overexpressed in prostate cancers but also in variety of solid tumors including glioblastoma multiforme. The aim of the present study was to demonstrate PSMA expression in gliomas using Ga-PSMA-HBED-CC(PSMA 11) PET/CT.

Patients And Methods: Ten patients with initially MRI suspected and eventually histopathologically proven gliomas [8 males (age range 30-73 yr; mean age 51.

Clinical utility of Rhenium-hydroxyethylidene-1,1-diphosphonate as a bone pain palliative in multiple malignancies.

Rhenium-hydroxyethylidene-1,1-diphosphonate (Re-HEDP) is a clinically established radiopharmaceutical for bone pain palliation of patients with metastatic bone cancer. Herein, the effectiveness of Re-HEDP for the palliation of painful bone metastases was investigated in an uncontrolled initial trial in 48 patients with different types of advanced cancers. A group of 48 patients with painful bone metastases of lung, prostate, breast, renal, and bladder cancer was treated with 2.

Potential immunomodulatory effect of allelochemical juglone in mice vaccinated with BCG.

Juglone, a naphthoquinone is a known phytotoxic and cytotoxic allelochemical. Various anticancer studies suggest that pharmacological ROS insult and enzymes inhibited by juglone could be of therapeutic utility. In this study, we show that juglone induces immunomodulation in BCG-vaccinated mice.