Anil Kumar Mishra

Defence Research and Development Organisation | DRDO · Division of Cyclotron and Radiopharmaceutical Sciences

A new era in tumor classification, diagnosis, and prognostic evaluation has begun as a consequence of recent developments in the molecular and genetic characterization of central nervous system tumors. In this newly emerging era, molecular imaging modalities are essential for preoperative diagnosis, surgical planning, targeted treatment, and post-t...

The pharmacologically characterized receptor subtype of the serotonin family, the 5HT1A receptor is implicated in the pathophysiology and treatment of depression and anxiety-related disorders. Being the most extensively targeted receptor for developing novel antidepressants and anxiolytics, a near-ideal theoretical model can aid in high-throughput...

Early prognosis of infection has been a major concern for clinicians worldwide. The diagnostic investigation in clinical practice focuses on resolving the complex mysteries of the deep-seated systemic infections, which are often difficult to decipher. Amongst the infectious diseases, the bacterial infections are the most ubiquitously found infectio...

The proposed study involves delivering drug/bioactive using a single nanoplatform based on PLGA for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were...

Serotonin receptor subtypes are predominantly accountable for various neurophysiologic and cognitive processes and are expressed in the hippocampus region. SPECT based radioligands offer a cost effective understanding to the molecular changes which are used in the diagnoses of various neurological disorders. A Homobivalent approach was used to synt...

High altitude pulmonary edema (HAPE) is generally characterized by the loss of alveolar epithelial barrier integrity. The current study was undertaken to assess the noninvasive approaches of HAPE diagnosis and to evaluate the prophylactic potential of quercetin in preventing alveolar junction impairments. Male SD rats fed with quercetin 1 h prior t...

PurposeAlzheimer’s disease (AD) is a progressive neurodegenerative pathological condition that resulted from the deterioration of cholinergic neurons over time. The pathological hallmark features of AD include extracellular β-amyloids plaques, hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFT) and neur...

An analog of γ1 laminin (RDIAEIIKDI) decapeptide has been used to augment neuronal survival and regeneration after injuries, during aging and other CNS disorder. As a prime synthetic peptide, KDI, is responsible for the neurite outgrowth of human embryonic neurons. In this study, we have designed, modified a KDI derivative and synthesized by replac...

Contrast enhancement in MRI using magnetization or saturation transfer techniques promises better sensitivity, and faster acquisition compared to T1 or T2 contrast. This work reports the synthesis and evaluation of 5-HT1A targeted PARACEST MRI contrast agent using 1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide (DO3AM) as the bifunctional chelat...

Development of a biodegradable nanoplatform poly(lactic-co-glycolic acid) (PLGA) for co-delivery of two drugs is hugely imperative and beneficial in anticancer therapeutics. In this study, co-delivery of a natural phytoconstituent, crocin (carotenoid), and a commonly prescribed drug, doxorubicin, was attempted using a nanoparticulate platform in th...

Peptides-coupled imaging agents are emerging as a new tool for early diagnosis with low adverse effects. Peptide-receptor based radiolabeled complex with good affinity to target specific receptors in cancers are required for imaging and quantification. Receptor mediated targeting of tumors for diagnosis, therapy or both is an encouraging approach a...

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. 68Ga-based generator and radiotracers render independence from the on-site cyclotron....

Bifunctional chelate EDTA-bis amide (N,N’-bis (tyramide)ethylenediamine-N,N’-diacetic acid) that has ability to mimic natural amino acids was synthesized and analyzed by various spectroscopic techniques. The physicochemical studies were performed to calculate the various thermodynamic and kinetic parameters for the synthesized poly-amino carboxylat...

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. ⁶⁸Ga-based generator and radiotracers render independence from the on-site cyclotron....

Background: The present study evaluated the prognostic value of [99mTc]MDM (bis-methionine-DTPA) follow-up single-photon emission computed tomography (SPECT) imaging for response assessment to chemoradiotherapy in glioma postoperatively. Materials and Methods: One hundred fourteen glioma patients (80 M:34 F) were followed postoperatively by sequen...

Objective: To characterize glioma preoperatively using quantitative 99mTc-methionine SPECT and comparison with MR-perfusion/spectroscopy and histopatholgical/Ki-67 scoring. Methods: Twenty-nine patients (21M: 8F; mean age 42.3 ± 10.5 years) with clinical and radiological suspicion of glioma assessed by 99mTc-MDM/SPECT and ceMRI. Additionally, 12...

National Conference on Nano/Bio-Technology, Special Center for Nanoscience Organized By Jawaharlal Nehru University & National Institute of Immunology, Delhi at Convention Center, JNU, New Delhi, 11-13 december 2019

Vascular endothelial growth factor co‐receptor neuropilin‐1, NRP‐1, is one of the prime tumor targets owing to its overexpression in numerous carcinomas. A peptidic conjugate, DO3A−Et‐RPAR was synthesized in 97% purity. It was labeled with 99mTc in 98% efficiency and specific activity of 3.62 MBq/nmol. The agent displayed minimal toxicity of 15% in...

The adverse effects of ionizing radiation (IR) on biological tissues are mediated via increased production of reactive oxygen species (ROS) often resulting in life-threatening injuries. The effects of ionizing radiation on cells include the formation of ROS, DNA single-strand breaks, double-strand breaks, and extensive base modifications inducing t...

Mapping different structural forms of serotonin subtypes 5-HT1A–5-HT7 using a selective-specific ligand with good pharmacokinetics and brain permeability can open avenues for personalized medication in depressed population. Herein, the selective 5-HT1A/7 antagonist, modified for enhanced brain permeation, is developed as a homobivalent ligand, (6-A...

Acetylcholinesterase (AChE) has been an important biomarker for diagnosing Alzheimer’s disease (AD), due to reduction in AChE activity in postmortem brains of AD patients. A potent, selective and reversible homodimeric inhibitor of acetylcholinesterase (AChE), 5-amino-N1,N3-bis(2-(1,2,3,4-tetrahydroacridin-9-ylamino)ethyl)isophthalamide [Compound (...

The antimicrobial peptide fragment GF-17 was synthesized in-house and conjugated with DOTA and measured molecular mass of DOTA-GF-17 conjugate was 2489 Da. The peptide conjugate was purified and labeled with [ ⁶⁸ Ga]. The best radiolabeling efficiency (95.0%) of [ ⁶⁸ Ga]DOTA-GF-17 was achieved at pH 4 with peptide conjugate amount of 20.0 nmol with...

Despite being in routine for onco-diagnostics for years, the applicability of nucleosidic molecular imaging probes is severely restricted in neurological applications due to their low permeability across blood-brain-barrier (BBB). For extending nucleoside tracers utility for neuro-onco early diagnostics, suitable modification which enhances their B...

The present study was to develop etoposide loaded solid lipid nanoparticles (SLN) and optimize it for effective ocular delivery to the posterior eye. SLN were prepared by melt-emulsification and ultrasonication technique. Etoposide loaded SLN were optimized by using three-factor three levels Box-Behnken design to establish the functional relationsh...

Development of homodimeric SPECT imaging ligand for targeting neuritic plaques formed in cases of Traumatic Brain Injury.

Some quaternary gemini amphiphiles (GAs) were synthesized as nonviral gene delivery carriers. The critical miceller concentration values of these amphiphiles are indicative of their superior surface-active properties. All of the synthesized GAs, alone or along with lipids like cholesterol and/or dioleoylphosphatidyl ethanolamine (DOPE), were formul...

A mixed affinity dimeric radioligand 99mTc-(BTZ)2DTPA was designed using a “bivalent ligand approach” and evaluated as an SPECT imaging agent for targeting 5-HT1A/5-HT7 dimeric receptors in the central nervous system. In silico studies reflected high affinity for dimeric 5-HT1A/5-HT7 receptors. Following multi-step synthesis, the ligand was obtaine...

Objective: Brain tumor research and medical practice have advanced over the past decades, but progress, while significant, has been incremental and slow. Nucleosides are structural modules of nucleic acids and play fundamental role in all biosystems.Their enhanced uptake in the rapidly proliferating cells like tumor leads to a differential concentr...

A new S-alkylated cysteine-derivatized tumor targeting agent, 2,2′-(12-(2-((2-acetamido-2-carboxyethyl)thio)acetamido)-11,13-dioxo-1,4,7,10-tetraazacyclotridecane-4,7-diyl)diacetic acid was developed for positron emission tomography (PET) imaging. N-Acetyl cysteine (NAC) was conjugated to ATRIDAT as a specific targeting agent toward L-type and ASC...

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis. Methods: CS-NPs were prepared by ionic gelation using tripolyphosphate. To specify pH sensitive delivery, CS-CN-NPs were coated w...

Objectives: Posttherapy changes in treated glioma patients cannot be reliably differentiated from tumor recurrence. We evaluated the role of Tc-methionine SPECT/CT for the detection of recurrent glioma and compared the same with F-FDG PET/CT and contrast-enhanced MRI (CeMRI). Methods: Forty-four patients with histologically proven, previously tr...

Shubhra Chaturvedi,1 Sangeeta Lal,2 Prasenjit Sen,3 Anil K Mishra1 1Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, Delhi, 2Department of Physics, B.S. College, Magadh University, Patna, Bihar, 3School of Physical Sciences, Jawaharlal Nehru University, New Delhi, Delhi, India Abs...

Purpose: In this study, Tc MDM (bis-methionine-DTPA) SPECT was used for the detection and differentiation of recurrent/residual glioma from radiation necrosis and the results were compared with dynamic susceptibility contrast-enhanced (DSCE)-MRI and clinical findings. Materials and methods: Twenty-eight patients (18 men and 10 women; mean ± SD a...

Abstract Successful delivery of chemotherapeutic agent like bendamustine still remains a challenge in the clinical conditions like Chronic lymphatic leukemia (CLL), Non-Hodgkin lymphoma (NHL) and multiple myeloma. We have conjugated bendamustine to Polyamidoamine (PAMAM) dendrimers after conjugating with N-hydroxyethylmaleimide (spacer) via an este...

The critical role of serotonin (5-hydroxytryptamine; 5-HT) and its receptors (5-HTRs) in the pathophysiology of various neuropsychiatric and neurodegenerative disorders render them attractive diagnostic/therapeutic targets for brain disorders. Therefore, in vivo assessment of binding of 5-HT receptor ligands under a multitude of physiologic and pat...

The subtype, 5-HT7R has been implicated in neurological disorders and presents itself as a promising target for antidepressant drugs. Design of targeted selective ligands, require a sound knowledge of 3D-receptor structure. In absence of receptor structure, structure-based design of targeted ligands relies on generation of 5-HT7R homology model. In...

Advanced malignant stage of pancreatic cancer has poor prognosis and very few treatment strategies are available. Pancreatic cancer is known to possess unique growth-related receptors that when activated stimulate tumour proliferation. Gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of this cancer t...

Polymer based nanoparticles have proven to be viable carriers of therapeutic agents. In this study we have developed nanoparticles (NPs) from polypeptide-polyethylene glycol based triblock and diblock copolymers. The synthesized block copolymers Poly (ethylene glycol)-b-Poly (glutamic acid)-b- Poly (ethylene glycol) (GEG) and Poly (ethylene glycol)...

Objective Metastasis of the osseous tissue is one of the frequent and severe aggravations as a result of several neoplastic conditions, such as metabolic disorders, infections, and cancer. The objective of this study was to evaluate the pertinence of [⁶⁸Ga]-trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid (CDTMP) as a potential bone ima...

The growing epidemiological and economic burden of neurological diseases on society is tremendous. A correct and timely diagnosis can help in lowering the burden and improving the life quality of both the diseased person and the caretaker. Imaging of the brain (neuroimaging) using CT, MRI, and nuclear imaging methods can provide anatomical and func...

Correct staging is the most crucial for the treatment outcome in cancer management. Molecular imaging with 18F-fluoroestradiol (FES) positron emission tomography-computed tomography (PET-CT) targets estrogen receptor (ER) and may have a higher incremental value in diagnosis by aiding specificity. We enrolled 12 female breast cancer patients prospec...

With the rising incidences of cancer cases, the quest for new metal based anticancer drugs has led to extensive research in cancer biology. Zinc complexes of amino acid residue side chains are well recognized for hydrolysis of phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II) complex of cyclen substituted with two L-tryptop...

Purpose: The study purposes to evaluate nanocrystalline biopolymeric nanoparticles encapsulating methotrexate and dexamethasone with high biocompatibility, enhanced therapeutic efficacy and reduced toxicity. Methods: Chitosan nanoparticles were prepared by ionic gelation, and Methotrexate (MTX) and Dexamethasone (DEX) were loaded during the prep...

We have synthesized six new congeners of acetamido-benzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8 ± 1.2 nM) for TSPO was found for N-methyl-2-(5-(naphthalen-1-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-phenylacetamide, (NBMP). NBMP was synthesised by suzuki coupling reaction between 2-(5-bromo-2-oxo...

Rational design of a new class of MR (magnetic resonance) contrast agent for enhance relaxivity has been described. The click chemistry was employed to incorporate two moieties of 1-(2-methoxyphenyl)piperazine and serinol as a linker to enhance the affinity at the recognition sites. The designed ligand was attached to DO3A to synthesize DO3A-serino...

The neuromedin B receptor (NMB-R) is a promising target in several human processes, for instance thymic carcinoma, intestinal carcinoids, pruritus, etc. NMB-R Positron Emission Tomography (PET) molecular imaging may be of great value. We here report on the development of the first 68Ga-ranatensin analog. The ranatensin derivative (Aib-Gln-Trp-Ala-V...

A new macrocyclic system 2,2’-(12-amino-11,13-dioxo-1,4,7,10-tetraazacyclotridecane-4,7-diyl)diacetic acid (ATRIDAT) was designed for coordinating metals in +2 and +3 oxidation states particularly 68Ga(III), for PET imaging. ATRIDAT was conjugated to biotin for pretargeting via biotin-avidin interaction. This model provides high tumor targeting eff...

Magnetic resonance imaging (MRI) is a diagnostic and research technique widely used in clinical research. We describe here a novel and facile synthesis of a bisconjugated triazaspirodecanone moiety using 'click chemistry' as a key step in the synthesis of a triazole based macrocyclic MRI contrast agent. A bivalent approach has been applied to conju...

A silent epidemic of modern world and largely neglected field in drug development is traumatic brain injury. There is no treatment available for the patients suffering from brain trauma. Peptide is a naturally occurring biological alternative that could represent a new generation of future medications. In this study, we have designed and modified t...

Neuromedin B receptor (NMB-R) is a promising target in several human processes, for instance thymic carcinoma, intestinal carcinoids but also pruritus, etc. NMB-R Positron Emission Tomography (PET) molecular imaging may be of great value. We here report on the development of the first 68Ga-ranatensin analog. The ranatensin derivative (Aib-Gln-Trp-A...

31 Objectives Simultaneous PET/MRI offers opportunity to evaluate glioma recurrence both with O-(2-18F-fluoroethyl)-L tyrosine (FET) PET and MRI together in a single examination in a short period of time. Kinetic evaluation using 40-50 minutes dynamic besides routine static FET-PET has shown to help differentiate tumor recurrence from reactive lesi...

The synthesis of estradiol based bivalent ligand [(EST) 2 DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethyl-amine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to fo...

The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form...

Theranostic liposomes are effective drug delivery systems for the management of infections. With added features of targeting and stealth, theranostic liposomes can be made more effective. We report the synthesis and validation of targeted stealth theranostic liposomes for the management of mycobacterial infections. The targeted drug delivery system...

Aim: Paclitaxel (PTX) is an effective anticancer agent used in the therapy of a wide variety of cancers. However, the drug is difficult to formulate due to its low solubility, and therefore, it is administered under slow infusion with castor oil/ethanol solution as surfactant that causes serious side effects. This investigation investigates leutin...

Primary hyperparathyroidism is caused by parathyroid adenomas in 85% of the cases. Since parathyroid adenomas are known for their ectopic location, presurgical localization of the suspected site of adenoma is desirable. However, current imaging modalities are not always successful in localizing ectopic parathyroid adenomas. The aim of this case rep...

Radiopharmaceuticals are an integral component of nuclear medicine and are widely applied in diagnostics and therapy. Though widely applied, the development of an “ideal” radiopharmaceutical can be challenging. Issues such as specificity, selectivity, sensitivity, and feasible chemistry challenge the design and synthesis of radiopharmaceuticals. Ov...

Purpose: This study aimed to investigate the potential of hybrid gadolinium (Gd)-enhanced 18F-fluoroethyl-L-tyrosine (18F-FET) PET/MRI in distinguishing recurrence from radiation necrosis using simultaneously acquired multiple structural and functional parameters. Methods: Twenty-six patients (5 female and 21 male patients; mean +/- SD age, 51.58 +...