On the automated radiosynthesis of pharmaceutical grade [Ga]Ga-Pentixafor, its pre-clinical evaluation, clinical application and radiation dosimetry aspects.

The current study outlines a consistent and reproducible protocol for the routine clinical dose preparation of [Ga]Ga-Pentixafor using the Eckert and Ziegler 'Modular-Lab Standard' non-cassette based automated module, that can be effectively used in the hospital radiopharmacy unit of a high volume nuclear medicine centre. The pre-clinical studies (including in-vitro cell line studies, in-vivo PET/CT imaging and pre-clinical dosimetry) were conducted to show the promising potential of the product for clinical use in targeting CXCR4 tumor overexpression. PET/CT image of SCID mouse bearing lymphoma xenograft tumor, at 2 h post-injection, clearly delineated the tumor.

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.

Production of pharmaceutical grade [Tl]Thallous chloride using 30 MeV cyclotron.

Multiple patient doses of [Tl]TlCl has been produced using electrodeposited enriched Tl in 30 MeV cyclotron (Cyclone-30) with 28 MeV proton energy at 50 μA beam current for 8 h. Ion Exchange Column Chromatography (IECC) and liquid-liquid extraction has been employed for semi-automated radiochemical separation and purification of produced [Tl]TlCl. The produced [Tl]TlCl was used in coronary artery disease (CAD) patients.

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.

Preparation of [Ga]Ga-Chloride from Zn solid target for the synthesis of pharmaceutical grade [Ga]Ga-PSMA-11 and [Ga]Ga-DOTA-TATE.

Ga is produced from enriched zinc-68 target electrodeposited on copper base material which was irradiated with 15 MeV proton energy in 30 MeV cyclotron. A modified semi-automated separation and purification module was used to obtain pharmaceutical grade [Ga]GaCl in 35 ± 5 min. The quality of [Ga]GaCl produced was in accordance with Pharmeuropa 30.

A method to prevail false positive responses due to excess cations and viscous nature of Radiopharmaceuticals in Limulus Amebocyte Lysate Gel Clot test.

Objectives: Bacterial endotoxin test (BET) for detection and quantification of endotoxin in radiopharmaceuticals (RPs), used for therapy or diagnosis, is prerequisite to administration in patients. Out of the two established methods used for this purpose (Kinetic Chromogenic Assay: KCM and Gel Clot Bacterial Endotoxin Test: GC-BET), GC-BET is recommended by pharmacopeias to evaluate the interferences exhibited during the assay due to presence of various ingredients in samples. In the present study, the influence of excess of cations in [Lu]Lu-DOTATATE, used for Peptide Receptor Radionuclide Therapy (PRRT), were studied and a protocol to negate the enhancement observed was developed.

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.

Clinical doses production of pharmaceutical grade Sodium[F]Fluoride using modified integrated fluidic processor in a SYNTHERA® module.

A fully automated large-scale production of sodium [F]fluoride ([F]NaF) using SYNTHERA module with a modification in integrated fluidic processor (IFP) is reported. This modified IFP module is used to prepare [F]NaF with more than 98% non-decay corrected radiochemical yield (RCY) within 5 min with specifications in accordance with United State Pharmacopeia (USP) monograph. The graphical user interface (GUI) is designed to perform the synthesis steps either manually or automatically and give information to the operator during the course of production.

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.

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].

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.

Radiochemical studies, pre-clinical investigation and preliminary clinical evaluation of Tm-EDTMP prepared using in-house freeze-dried EDTMP kit.

The objective of the present work is to formulate Tm-EDTMP using an in-house freeze-dried EDTMP kit and evaluate its potential as a bone pain palliation agent. Patient dose of Tm-EDTMP was prepared with high radiochemical purity using the lyophilized kit at room temperature within 15min. Pre-clinical evaluation in normal Wistar rats revealed selective skeletal accumulation with extended retention.

Limulus amebocyte lysate testing: adapting it for determination of bacterial endotoxin in 99mTc-labeled radiopharmaceuticals at a hospital radiopharmacy.

Unlabelled: A bacterial endotoxin test (BET) is required to detect or quantify bacterial endotoxin that may be present in radiopharmaceutical preparations. The test uses Limulus amebocyte lysate, which, in the presence of bacterial endotoxin and divalent calcium ions, causes the formation of a coagulin gel. (99m)Tc-labeled radiopharmaceuticals have chelating ligands such as diethylene triamine pentaacetic acid (DTPA), ethylene dicysteine (EC), L,L-ethyl cysteinate dimer (ECD), N-[2,4,6-trimethyl-3 bromoacetanilid] iminodiacetic acid (mebrofenin), dimercapto succinic acid-III (DMSA-III), dimercapto succinic acid-V (DMSA-V), and several others, which form a coordination complex with Na-(99m)Tc-O4 in the presence of reducing agents.