PURPOSE: The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of ⁶⁸Ga-labeled RGD peptide derivatives.METHODS: The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]₂, DOTA-Bn-E-[c(RGDfk)]₂, and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled with ⁶⁸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the ⁶⁸Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration.RESULTS: NOTA-Bn-E-[c(RGDfk)]₂ could be radiolabeled with ⁶⁸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]₂ and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled at high temperature. ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was the best amongst the three radiotracers. ⁶⁸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]₂ and DOTABn-E-[c(RGDfk)]₂ showed excellent in vivo stability while ⁶⁸Ga-DTPA-Bn-E-[c(RGDfk)]₂ showed significant metabolic degradation.CONCLUSION: These studies show that ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ would be the most appropriate ⁶⁸Ga-labeled radiotracer and the most amenable for kit formulation.
Animals ; Chelating Agents ; In Vitro Techniques ; Melanoma ; Mice ; Pentetic Acid ; Peptides

BACKGROUND AND OBJECTIVES: Stress echocardiography is the current standard for cardiac risk stratification of patients undergoing orthotopic liver transplantation (OLT). We aim to evaluate the role of dobutamine stress echocardiography (DSE) in predicting perioperative major adverse cardiac event (MACE) in patients undergoing OLT. METHODS: This was a single-center retrospective study including 144 OLT patients. Of 144 patients, 118 had DSE. MACE included myocardial infarction (MI), heart failure (HF), cardiovascular and all-cause death 1 year after OLT. RESULTS: Our study cohort included 118 patients. The mean age was 57.3±8.2 years (range, 25–72 years). There were 85 men and 33 women, male to female ratio being 2.6:1. Of 118, 15 (13%) had positive DSE and 103 (87%) had negative DSE. Perioperative MACE incidence was 5.9% (95% confidence interval [CI], 2.6–12.3%). In predicting MACE, DSE had sensitivity of 5.6% (95% CI, 0.2–29.4%), specificity 86% (95% CI, 77.3–91.9%), positive predictive value 6.7% (95% CI, 0.3–33.4%), and negative predictive value (NPV) 83.5% (95% CI, 74.6–89.8%). Eighteen patients had MACE in first year post OLT (15%, 95% CI, 9.5–23.3%). Adverse events included cardiogenic shock (2/18), systolic HF (2/18), non-ST-elevated MI (7/18), cardiac mortality (3/18), and all-cause mortality (7/18). The overall complication rate of DSE was 17% (20/118). CONCLUSIONS: In our cohort, DSE had a low sensitivity but high NPV in predicting perioperative MACE post OLT. A similar trend was noted for DSE in predicting 1-year MACE post OLT. We reiterate the need of a better screening and risk stratification tool for OLT.
Cohort Studies ; Coronary Artery Disease ; Dobutamine ; Echocardiography, Stress ; Female ; Heart Failure ; Humans ; Incidence ; Liver Transplantation ; Liver ; Male ; Mass Screening ; Mortality ; Myocardial Infarction ; Retrospective Studies ; Sensitivity and Specificity ; Shock, Cardiogenic

BACKGROUND AND OBJECTIVES: Stress echocardiography is the current standard for cardiac risk stratification of patients undergoing orthotopic liver transplantation (OLT). We aim to evaluate the role of dobutamine stress echocardiography (DSE) in predicting perioperative major adverse cardiac event (MACE) in patients undergoing OLT. METHODS: This was a single-center retrospective study including 144 OLT patients. Of 144 patients, 118 had DSE. MACE included myocardial infarction (MI), heart failure (HF), cardiovascular and all-cause death 1 year after OLT. RESULTS: Our study cohort included 118 patients. The mean age was 57.3±8.2 years (range, 25–72 years). There were 85 men and 33 women, male to female ratio being 2.6:1. Of 118, 15 (13%) had positive DSE and 103 (87%) had negative DSE. Perioperative MACE incidence was 5.9% (95% confidence interval [CI], 2.6–12.3%). In predicting MACE, DSE had sensitivity of 5.6% (95% CI, 0.2–29.4%), specificity 86% (95% CI, 77.3–91.9%), positive predictive value 6.7% (95% CI, 0.3–33.4%), and negative predictive value (NPV) 83.5% (95% CI, 74.6–89.8%). Eighteen patients had MACE in first year post OLT (15%, 95% CI, 9.5–23.3%). Adverse events included cardiogenic shock (2/18), systolic HF (2/18), non-ST-elevated MI (7/18), cardiac mortality (3/18), and all-cause mortality (7/18). The overall complication rate of DSE was 17% (20/118). CONCLUSIONS In our cohort, DSE had a low sensitivity but high NPV in predicting perioperative MACE post OLT. A similar trend was noted for DSE in predicting 1-year MACE post OLT. We reiterate the need of a better screening and risk stratification tool for OLT.

Tissue engineering is a research domain that deals with the growth of various kinds of tissues with the help of synthetic composites. With the culmination of nanotechnology and bioengineering, tissue engineering has emerged as an exciting domain. Recent literature describes its various applications in biomedical and biological sciences, such as facilitating the growth of tissue and organs, gene delivery, biosensor-based detection, etc. It deals with the development of biomimetics to repair, restore, maintain and amplify or strengthen several biological functions at the level of tissue and organs. Herein, the synthesis of nanocomposites based on polymers, along with their classification as conductive hydrogels and bioscaffolds, is comprehensively discussed. Furthermore, their implementation in numerous tissue engineering and regenerative medicine applications is also described. The limitations of tissue engineering are also discussed here. The present review highlights and summarizes the latest progress in the tissue engineering domain directed at functionalized nanomaterials.

PURPOSE: The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of ⁶⁸Ga-labeled RGD peptide derivatives. METHODS: The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]₂, DOTA-Bn-E-[c(RGDfk)]₂, and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled with ⁶⁸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the ⁶⁸Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration. RESULTS: NOTA-Bn-E-[c(RGDfk)]₂ could be radiolabeled with ⁶⁸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]₂ and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled at high temperature. ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was the best amongst the three radiotracers. ⁶⁸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]₂ and DOTABn-E-[c(RGDfk)]₂ showed excellent in vivo stability while ⁶⁸Ga-DTPA-Bn-E-[c(RGDfk)]₂ showed significant metabolic degradation. CONCLUSION These studies show that ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ would be the most appropriate ⁶⁸Ga-labeled radiotracer and the most amenable for kit formulation.