Evaluation of Lu-Labeled Pertuzumab F(ab') Fragments for HER2-Positive Cancer Targeting: A Comparative and Study.

Radiolabeled antibody fragments present a promising opportunity as theranostic agents, offering distinct advantages over whole antibodies. In this study, the authors investigate the potential of [Lu]Lu-DTPA-F(ab')-pertuzumab as a theranostic agent for precise targeting of human epidermal growth factor receptor 2 (HER2)-positive cancers. Additionally, the authors aim to quantitatively assess the binding synergism in the presence of cold trastuzumab.

Imaging of bacterial infection: Harnessing positron emission tomography and Cherenkov luminescence imaging with UBI-derived octapeptide.

Noninvasive imaging techniques for the early detection of infections are in high demand. In this study, we present the development of an infection imaging agent consisting of the antimicrobial peptide fragment UBI (31-38) conjugated to the chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), which allows for labeling with the positron emitter Ga-68. The preclinical evaluation of [ Ga]Ga-NODAGA-UBI (31-38) was conducted to investigate its potential for imaging bacterial infections caused by Staphylococcus aureus.

Synthesis and Lu Labeling of the First Retro Analog of the HER2-Targeting A9 Peptide: A Superior Variant.

The retro analog of the HER2-targeting A9 peptide was synthesized by coupling amino acids in a reverse fashion and switching the N-terminal in the original sequence of the L-A9 peptide (QDVNTAVAW) to the C-terminal in rL-A9 (WAVATNVDQ). Modification in the backbone resulted in higher conformational stability of the retro peptide as evident from CD spectra. Molecular docking analysis revealed a higher HER2 binding affinity of [Lu]Lu-DOTA-rL-A9 than the original radiopeptide [Lu]Lu-DOTA-L-A9.

Biochemical separation of Cetuximab-Fab from papain-digested antibody fragments and radiolabeling with Cu for potential use in radioimmunotheranostics.

Engineered Fab fragments of monoclonal antibodies (mAbs) after radiolabeling with suitable radiometals have the potential to play a key role in personalized radioimmunotheranostics of cancer patients. In this study, we have generated Fab fragment of Cetuximab, a mAb targeting epidermal growth factor receptor (EGFR) expression and purified from the Fc and other fragments by ultrafiltration and affinity chromatography. The Cetuximab-Fab was conjugated with a suitable bifunctional chelator and radiolabeled with no-carrier-added (NCA) Cu produced via Zn (n, p) Cu reaction in a nuclear reactor.

[Tc]Tc-HYNIC-RM2: A potential SPECT probe targeting GRPR expression in prostate cancers.

Introduction: Elevated density of gastrin releasing peptide receptors (GRPR) in prostate cancer has led to exploration of several radiolabeled peptides for imaging and staging of the disease. The GRPR antagonist peptide RM2 has been successfully conjugated with several chelators and radiolabeled with gallium-68. The goal of this study was to synthesize a Tc-labeled probe and investigate its potential for SPECT imaging of prostate cancer.

Evaluation of the effect of a cell penetrating peptide (TAT) towards tailoring the targeting efficacy and tumor uptake of porphyrin.

Cell penetrating peptides (CPPs) are known to possess a unique capacity to penetrate biological membranes and translocate various molecules into the cells. Therefore, porphyrin-CPP conjugates could be envisaged to boost the intracellular delivery of porphyrins thereby providing an improved tool for the development of agents for multi-modal applications for cancer management. Working in this direction, an unsymmetrically substituted porphyrin derivative was conjugated with a transactivating transcriptional activator peptide (TAT) and various and  studies were carried out in order to study the effect of adding a CPP to the porphyrin derivative.

Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers.

Trastuzumab, the first humanized antibody approved for therapeutic use has shown promising results for the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive cancers. The aim of this study was to formulate immunoPET agents based on trastuzumab fragments and demonstrate their potential for early diagnosis of HER2-positive tumors. F(ab') and F(ab') fragments of trastuzumab were prepared by enzymatic digestion and conjugated with chelator NOTA for labeling with Ga.

Synthesis and comparative evaluation of Lu-labeled PEG and non-PEG variant peptides as HER2-targeting probes.

Highest global cancer incidence of female breast cancer is a matter of great concern. HER2-positive breast cancers have high mortality rate hence detection at an early stage is vital for successful treatment, improved cancer care and survival rate. Radiolabeled peptides have emerged as new alternatives to radiolabeled antibodies to overcome the limitations of slow clearance and uptake in non-target tissues.

Synthesis and evaluation of [ Lu]Lu-labeled porphyrin loaded PAMAM dendrimer: Impact on tumor uptake and pharmacokinetics.

The objective of the present work is to evaluate the ability of the radiolabeled PAMAM dendrimers (polyamidoamine) towards facilitating the delivery of an in-house synthesized porphyrin derivative in the tumorous lesions to evaluate their candidature for possible application in endo-radionuclide therapy. For this, PAMAM particles were conjugated with a porphyrin derivative namely, 5,10,15,20-tetrakis-(4-carboxymethyleneoxyphenyl)porphyrin (STAP), synthesized in-house following a two-step reaction. The average number of porphyrin molecules loaded per PAMAM particle was evaluated using ultraviolet-visible spectrophotometry and was found to be approximately 2.

A solvent extraction-based procedure for removal of Sc impurity from reactor produced [Ca]CaCl for its potential use in bone pain palliation.

Calcium-45 [T = 163 d, E (max) = 0.3 MeV] is a pure β emitting radioisotope which can be envisaged for potential use in palliative care of pain due to skeletal metastases of primary cancer. During production of Ca in nuclear reactor via Ca (n,γ) Ca route, Sc is co-produced as a radionuclidic impurity.

Multimodal Applications of Zinc Gallate-Based Persistent Luminescent Nanoparticles in Cancer Treatment: Tumor Margining, Diagnosis, and Boron Neutron Capture Therapy.

On the basis of the boron neutron capture therapy (BNCT) modality, we have designed and synthesized a zinc gallate (ZnGaO)-based nanoformulation for developing an innovative theranostic approach for cancer treatment. Initially, the (ZnGaCrO or ZnGaO:(0.5%)Cr persistent luminescence nanoparticles (PLNPs) embedded on silica matrix were synthesized.

Effect of ovarian follicular wave pattern and endocrine characteristics on pregnancy outcome in cows.

The effect of two (2W) versus three (3W) wave patterns of follicular dynamics and concurrent endocrine milieu of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol 17-β (E2) and progesterone (P4) were investigated during one interoestrous interval (IEI) before insemination, on ensuing pregnancy, in 70 lactating Jersey crossbred cows. The findings were evaluated for between [included all (overall) 2W-O and 3W-O cows] and within [after separating pregnant (P) and non-pregnant (NP) cows in 2W and 3W] wave patterns. The propensity of two (58.

Preparation of Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.

Objective: In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of Lu-PSMA-617 patient doses can be made simpler and convenient, if the ingredients essential for radiolabeling are made available in a ready-to-use lyophilized form.

Methods: PSMA-617 freeze-dried kit was formulated and used for the preparation of Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity Lu.

Assessment of Lu-labeled carboxyl-terminated polyamidoamine (PAMAM) dendrimer-RGD peptide conjugate.

Structurally unique polyamidoamine (PAMAM) dendrimers implanted with targeting biological moiety along with complexed radiometal constitute a favorable nano-system for diagnosis and therapy of targeted tumor sites. In the present study, carboxyl functionalities of PAMAM- generation 4 dendrimer (PAMAM-G4-COOH) were conjugated with ε-amino group of lysine of cRGDfK peptide to impart integrin α β targeting capability. Reaction of p-NH -Bn-DOTA with PAMAM was accomplished via acid-amine coupling using EDC/NHS for Lu-complexation.

Formulation and clinical translation of [Lu]Lu-trastuzumab for radioimmunotheranostics of metastatic breast cancer.

Trastuzumab (Herceptin®) is an approved immunotherapeutic agent used for the treatment of metastatic breast cancer over-expressing HER2 antigen receptors. The aim of the present work is to standardize the formulation protocol of [Lu]Lu-trastuzumab addressing various reaction parameters, evaluating the efficacy of the radiolabeled product by investigations, scaling-up the preparation for administration in patients and performing preliminary clinical studies in patients suffering from metastatic breast cancer. Trastuzumab was conjugated with a suitable bi-functional chelating agent namely, -NCS-benzyl-DOTA.

Ga-labeled PET tracers for targeting tumor hypoxia: Role of bifunctional chelators on pharmacokinetics.

Introduction: By virtue of their oxygen dependant accumulation in hypoxic cells, radiolabeled nitroimidazole analogues have been widely used for detecting tumor hypoxia. Present study evaluates two 2-nitroimidazole (2-NIM) based Ga-labeled radiotracers, [Ga]Ga-DOTAGA-2-NIM and [Ga]Ga-NODAGA-2-NIM, for hypoxia targeting applications.

Methods: Bifunctional chelating agents suitable for radiolabeling with Ga, viz.

Effect of structural variation on tumor targeting efficacy of cationically charged porphyrin derivatives: Comparative in-vitro and in-vivo evaluation for possible potential in PET and PDT.

tetracationic (TMPyP) and tricationic porphyrin (TriMPyCOOHP) derivatives were synthesized, characterized and investigated for binding with DNA by Isothermal Titration Calorimetry as well as by UV-Vis spectroscopy in order to study the effect of structural variation on tumor targeting efficacy of cationically charged porphyrin derivatives. Fluorescence cell imaging studies performed in cancer cell lines corroborated the findings of aforementioned studies. Photocytotoxicity experiments in A549 cell lines revealed relatively higher light dependent cytotoxic effects exerted by TMPyP compared to TriMPyCOOHP.

Pharmacological characterization of a structurally new class of antibacterial compound, triphenyl-phosphonium conjugated diarylheptanoid: Antibacterial activity and molecular mechanism.

Many pathogenic species of bacteria are showing increasing drug resistance against clinically used antibiotics. Molecules structurally distant from known antibiotics and possessing membrane targeting bactericidal activities are more likely to display activity against drug-resistant pathogens. Mitocurcumin (MitoC) is one of such compounds, synthesized by triphenyl-phosphonium conjugation with curcumin, and has been shown recently from our laboratory to have broad-spectrum bactericidal activity (Kumari 2019 143, 140-145).

Reactor produced [Cu]CuCl as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic.

Objective: Copper-64 is a useful theranostic radioisotope that is attracting renewed interest from the nuclear medicine community in the recent times. This study aims to demonstrate the utility of research reactors to produce clinical-grade Cu via Cu(n,γ)Cu reaction and use it in the form of [Cu]CuCl as a radiopharmaceutical for PET imaging of cancer in human patients.

Methods: Copper-64 was produced by irradiation of natural CuO target in a medium flux research reactor.

Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with Lu-Acridine.

Objective: A DNA intercalating agent reversibly stacks between the adjacent base pairs of DNA and thus is expected to exhibit preferential localization in the tumorous lesions as tumors are associated with enhanced DNA replication. Therefore, radiolabeled DNA intercalators are supposed to have potential to be used in targeted tumor therapy. Working in this direction, an attempt was made to radiolabel 9-aminoacridine, a DNA intercalator, with Lu, one of the most useful therapeutic radionuclides, and study the potential of Lu-acridine in targeted tumor therapy.

A simple and robust method for radiochemical separation of no-carrier-added Cu produced in a research reactor for radiopharmaceutical preparation.

Copper-64 is an excellent theranostic radiometal that is gaining renewed attention of the clinical community in the recent times. In order to meet the increasing demand of this radiometal, we have demonstrated the viability of its production via Zn (n,p) Cu reaction in a nuclear reactor. A semi-automated radiochemical separation module based on selective extraction of Cu as dithizonate complex was developed.

Preparation and Preliminary Evaluation of 68Ga-Acridine: An Attempt to Study the Potential of Radiolabeled DNA Intercalator as a PET Radiotracer for Tumor Imaging.

Introduction: Acridine is a well-known DNA intercalator and thereby gets easily inserted within DNA. As uncontrolled rapid cell division is one of the primary characteristics of the tumors, it is expected that acridine or its suitable derivatives will have preferential accumulation in the tumorous lesions. Therefore, an attempt was made to radiolabel an acridine derivative with 68Ga and study the potential of the 68Ga-acridine complex as a PET agent for tumor imaging.

A kit based methodology for convenient formulation of Ho-Chitosan complex for treatment of liver cancer.

The effectiveness of Ho-chitosan complex as a radiopharmaceutical for trans-arterial radiation therapy of liver cancer has been established in clinical trials. We have developed a simple kit-bade strategy for convenient formulation of therapeutically relevant doses of Ho-chitosan complex in a hospital radiopharmacy in order to facilitate its widespread utilization. Quality control studies established the suitability of the radiopharmaceutical formulated using the developed strategy for in vivo administration.