Pretargeting : A concept refraining traditional flaws in tumor targeting

Bhise, Abhinav,Yoo, Jeongsoo Korean Society of Radiopharmaceuticals and Molecul 2020 Journal of radiopharmaceuticals and molecular prob Vol.6 No.1

Pretargeting is a two-component strategy often used for tumor targeting to enhance the tumor-to-background ratio in cancer diagnosis as well as therapy. In the multistep strategy, the highly specific unlabeled monoclonal antibodies (mAbs) with the reactive site is allowed to get localized at tumor site first, and then small and fastclearing radiolabeled chelator with counter reactive site is administered which covalently attaches to mAbs via inverse electron demand Diels-Alder reaction (IEDDA). The catalyst-free IEDDA cycloaddition reaction between 1,2,4,5-tetrazines and strained alkene dienophiles aid with properties like selective bioconjugation, swift and high yielding bioorthogonal reactions are emergent in the development of radiopharmaceutical. Due to its fast pharmacokinetics, the in vivo formed radioimmunoconjugates can be imaged at earlier time points by short-lived radionuclides like ¹⁸F and ⁶⁸Ga; it can also reduce radiation damage to the normal cells. Ultimately, this review elucidates the updated status of pretargeting based on antibodies and IEDDA for tumor diagnosis (PET and SPECT) and therapy.

Pretargeting : A concept refraining traditional flaws in tumor targeting

Abhinav Bhise,유정수 대한방사성의약품학회 2020 Journal of radiopharmaceuticals and molecular prob Vol.6 No.1

Pretargeting is a two-component strategy often used for tumor targeting to enhance the tumor-to-background ratio in cancer diagnosis as well as therapy. In the multistep strategy, the highly specific unlabeled monoclonal antibodies (mAbs) with the reactive site is allowed to get localized at tumor site first, and then small and fastclearing radiolabeled chelator with counter reactive site is administered which covalently attaches to mAbs via inverse electron demand Diels-Alder reaction (IEDDA). The catalyst-free IEDDA cycloaddition reaction between 1,2,4,5-tetrazines and strained alkene dienophiles aid with properties like selective bioconjugation, swift and high yielding bioorthogonal reactions are emergent in the development of radiopharmaceutical. Due to its fast pharmacokinetics, the in vivo formed radioimmunoconjugates can be imaged at earlier time points by short-lived radionuclides like 18F and 68Ga; it can also reduce radiation damage to the normal cells. Ultimately, this review elucidates the updated status of pretargeting based on antibodies and IEDDA for tumor diagnosis (PET and SPECT) and therapy.

Antibody radiolabeling with diagnostic Cu-64 and therapeutic Lu-177 radiometal

Abhinav Bhise,유정수 대한방사성의약품학회 2022 Journal of radiopharmaceuticals and molecular prob Vol.8 No.1

With the development of monoclonal antibodies, therapeutic or diagnostic radioisotope has been successfully delivered at tumor sites with high selectivity for antigens. Different approaches have been applied to improve the tumor-to-normal ratio by considering the in vivo stability of radioimmunoconjugates as a prerequisite. Various stable and inert antibody radiolabeling techniques for radioimmunoconjugate preparation have been extensively evaluated to enhance in vivo stability. Antibody radiolabeling techniques should be rapid and easy; they should not disrupt the immunoreactivity and in vivo behavior of antibodies, which are coupled with a bifunctional chelator (BFC) to stably coordinate with a radiometal. For the design of BFCs, radiometal coordination properties must be considered. However, various diagnostic radionuclides, such as 89Zr, 64Cu, 68Ga, 111In, and 99mTc, or therapeutic radionuclides, such as 177Lu, 67Cu, 90Y, and 225Ac, have been increasingly used for antibody radiolabeling. In addition to useful radionuclides, 64Cu and 177Lu with the most accessible or the highest production rates in many countries should be considered. In this review, we mainly discussed antibody radiolabeling techniques and conditions that involve 64Cu and 177Lu radiometals.

Synthesis of a PEGylated tracer for radioiodination and evaluation of potential in tumor targeting

Abhinav Bhise,Sushil K. Dwivedi,이기웅,임정은,수브라므니 라즈쿠말,이웅희,조성환,유정수 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radio-tracer at the desired target excluding non-targeted tissues is difficult. The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG36) with the introduction of a low molecular weight polyethylene glycol unit (PEG36, ~2100 Da). The tumor-targeting efficiency and biodistribution of [131I]-Bz-PEG36 or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

National Trends in Smoking Cessation Medication Prescriptions for Smokers With Chronic Obstructive Pulmonary Disease in the United States, 2007-2012

곽민지,김종오,Viraj Bhise,Tong Han Chung,Gabriela Sanchez Petitto 대한예방의학회 2018 Journal of Preventive Medicine and Public Health Vol.51 No.5

Objectives: Smoking cessation decreases morbidity and mortality due to chronic obstructive pulmonary disease (COPD). Pharmacotherapy for smoking cessation is highly effective. However, the optimal prescription rate of smoking cessation medications among smokers with COPD has not been systemically studied. The purpose of this study was to estimate the national prescription rates of smoking cessation medications among smokers with COPD and to examine any disparities therein. Methods: We conducted a retrospective study using National Ambulatory Medical Care Survey data from 2007 to 2012. We estimated the national prescription rate for any smoking cessation medication (varenicline, bupropion, and nicotine replacement therapy) each year. Multiple survey logistic regression was performed to characterize the effects of demographic variables and comorbidities on prescriptions. Results: The average prescription rate of any smoking cessation medication over 5 years was 3.64%. The prescription rate declined each year, except for a slight increase in 2012: 9.91% in 2007, 4.47% in 2008, 2.42% in 2009, 1.88% in 2010, 1.46% in 2011, and 3.67% in 2012. Hispanic race and depression were associated with higher prescription rates (odds ratio [OR], 5.15; 95% confidence interval [CI], 1.59 to 16.67 and OR, 2.64; 95% CI, 1.26 to 5.51, respectively). There were no significant differences according to insurance, location of the physician, or other comorbidities. The high OR among Hispanic population and those with depression was driven by the high prescription rate of bupropion. Conclusions: The prescription rate of smoking cessation medications among smokers with COPD remained low throughout the study period. Further studies are necessary to identify barriers and to develop strategies to overcome them.

Radioiodination strategies for carborane compounds

Rajkumar Subramani,Abhinav Bhise,유정수 대한방사성의약품학회 2022 Journal of radiopharmaceuticals and molecular prob Vol.8 No.1

The development of methods for the inert and stable radiohalogenation of targeted radiopharmaceuticals is a prerequisite for real-time diagnosis and therapy using radiohalogenated radiopharmaceuticals. Radiohalogenated carboranes demonstrate superior stability in vivo and versatile applications compared with directly labeled tyrosine analogues or synthetically modified organic compounds. Herein, we focus on the most common approaches for the radioiodination (123I, 124I, 125I, and 131I) of carborane derivatives.

Role of polyethylene glycol (PEG) linkers: trends in antibody conjugation and their pharmacokinetics

BOBBA KONDAPA NAIDU,Abhinav Bhise,수브라므니 라즈쿠말,이웅희,유정수 대한방사성의약품학회 2020 Journal of radiopharmaceuticals and molecular prob Vol.6 No.2

Polyethylene glycol (PEG) has been the most commonly used polymer for the past few decades in the field of biomedical applications due to its gold standard stealth effect. PEGylation of antibody–drug conjugates, liposomes, peptides, nanoparticles, and proteins is done to improve their pharmaceutical efficacy and pharmacokinetic properties. PEGylation of antibodies with various PEG linkers improves targeting ability by increasing the blood circulation time and thus enhances the biodistribution profiles. It also assists in minimizing the immediate capture by the reticuloendothelial system. In this review, we summarize the effect of PEG linkers in an antibody conjugation and their pharmacokinetics in the field of biomedical imaging.

Recent progress in selective bioconjugation

수브라므니 라즈쿠말,Abhinav Bhise,BOBBA KONDAPA NAIDU,유정수 대한방사성의약품학회 2020 Journal of radiopharmaceuticals and molecular prob Vol.6 No.2

Selective installation of proteins using chemical reagents is important for the development of potential biomaterials for the treatment of human diseases. However, modification in a chemo- and regioselective manner under physiological conditions is a great challenge due to the presence of multiple reactive centers in the protein. Currently, the majority of conjugations are limited to lysine (Lys)- and cysteine (Cys)-selective reagents. Thus, they have been extensively studied. Apart from Lys and Cys, widespread site selectivity has been recently achieved through most of the 20 naturally occurring amino acid-bearing reactive functional groups. Consequently, this review focused on several recent achievements in site-selective modification of the rarest amino acid backbones (e.g., methionine, serine, glutamic acid, and tyrosine).

Selective tyrosine conjugation with a newly synthesized PCB -TE2A-luminol bifunctional chelator

수브라므니 라즈쿠말,박현,Abhinav Bhise,조성환,김정영,이교철,유정수 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

Selective amino acid conjugation of bulky antibodies is a valuable asset for real-time diagnosis and therapy. However, selective conjugation incorporating a chelate-bearing radioactive atom into an antibody without affecting its immunoreactivity is a challenging task. A bifunctional chelator (BFC), a selective amino acid-targeting probe, and a linker have been developed to overcome this problem. Here, we report the synthesis of a novel propylene cross-bridged chelator (PCB)‒1,8-N,N′-bis-(carboxymethyl)-1,4,8,11-tetraazacyclotetradecane (TE2A)‒luminol BFC via a click reaction and radiolabel it with a 64Cu ion for tyrosine-selective conjugation of trastuzumab. In the initial optimization study, we tried different oxidative addition conditions such as electro-oxidation, hemin, horseradish peroxidase, iodogen tube, chloramine-T, and iodo beads. In this study, up to 82% of 64Cu-PCB-TE2A-luminol was conjugated with the antibody in an iodo bead-catalyzed oxidative addition reaction with an isolated yield of 24.4%.

Reversible Data Hiding Scheme Using Turbo Code

Vidya Sawant,Archana Bhise 대한전자공학회 2019 IEIE Transactions on Smart Processing & Computing Vol.8 No.6

A reversible data hiding scheme provides security for a secret message by embedding it in a cover image. After extracting the secret message at the receiver, the scheme restores the original message and the cover image without any distortion. However, data transmitted by the reversible data hiding scheme is vulnerable to the noise existing on the communications channel. A reversible data hiding scheme using turbo code is proposed in this paper to address that problem. The proposed reversible data hiding integrates modified matrix embedding, turbo code, and syndrome embedding to provide improved embedding capacity, security, and error correction. Modified matrix embedding hides the secret message in the cover image. The resulting stego-image is then encrypted and encoded by the turbo code. Turbo code deploys a secret key interleaver that shuffles the incoming bits using elliptic curve arithmetic and a secret key. The exact recovery of the cover image and the secret message by the receiver depends on the user-specific secret key. Modified matrix embedding hides a large number of secret message bits, which distorts the stegoimage. However, encrypting the stego-image with the secret key interleaver makes the embedding invisible. The proposed syndrome embedding transmits the locations of the modified bits in the cover image, and enables the receiver to reverse the effects of embedding. Simulation results with the proposed scheme demonstrate a high embedding capacity and improved error correction performance of 10-4 for an additive white Gaussian noise (AWGN) channel at an SNR of 2dB. It also successfully recovers the exact cover image and the secret message, compared to existing schemes such as matrix embedding and reversible data hiding in the encrypted domain. Moreover, the results depict high resistance to brute force attacks, statistical attacks, noise attacks, and cropping attacks.