scholarly journals Cardiac Targeting Peptide, a Novel Cardiac Vector: Studies in Bio-Distribution, Imaging Application, and Mechanism of Transduction

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 147 ◽  
Author(s):  
Maliha Zahid ◽  
Kyle Feldman ◽  
Gabriel Garcia-Borrero ◽  
Timothy Feinstein ◽  
Nicholas Pogodzinski ◽  
...  

Our previous work identified a 12-amino acid peptide that targets the heart, termed cardiac targeting peptide (CTP). We now quantitatively assess the bio-distribution of CTP, show a clinical application with the imaging of the murine heart, and study its mechanisms of transduction. Bio-distribution studies of cyanine5.5-N-Hydroxysuccinimide (Cy5.5) labeled CTP were undertaken in wild-type mice. Cardiac targeting peptide was labeled with Technetium 99m (99mTc) using the chelator hydrazino-nicotinamide (HYNIC), and imaging performed using micro-single photon emission computerized tomography/computerized tomography (SPECT/CT). Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMCs) were incubated with dual-labeled CTP, and imaged using confocal microscopy. TriCEPs technology was utilized to study the mechanism of transduction. Bio-distribution studies showed peak uptake of CTP at 15 min. 99mTc-HYNIC-CTP showed heart-specific uptake. Robust transduction of beating human iPSC-derived CMCs was seen. TriCEPs experiments revealed five candidate binding partners for CTP, with Kcnh5 being felt to be the most likely candidate as it showed a trend towards being competed out by siRNA knockdown. Transduction efficiency was enhanced by increasing extracellular potassium concentration, and with Quinidine, a Kcnh5 inhibitor, that blocks the channel in an open position. We demonstrate that CTP transduces the normal heart as early as 15 min. 99mTc-HYNIC-CTP targets the normal murine heart with substantially improved targeting compared with 99mTc Sestamibi. Cardiac targeting peptide’s transduction ability is not species limited and has human applicability. Cardiac targeting peptide appears to utilize Kcnh5 to gain cell entry, a phenomenon that is affected by pre-treatment with Quinidine and changes in potassium levels.

Author(s):  
Jinguo Zhang ◽  
Guanzhong Zhai ◽  
Bin Yang ◽  
Zhenhe Liu

Prostate cancer is one of the most common cancers in men. This cancer is often associated with indolent tumors with little or no lethal potential. Some of the patients with aggressive prostate cancer have increased morbidity and early deaths. A major complication in advanced prostate cancer is bone metastasis that mainly results in pain, pathological fractures, and compression of spinal nerves. These complications in turn cause severe pain radiating to the extremities and possibly sensory as well as motor disturbances. Further, in patients with a high risk of metastases, treatment is limited to palliative therapies. Therefore, accurate methods for the detection of bone metastases are essential. Technical advances such as single-photon emission computed tomography/ computed tomography (SPECT/CT) have emerged after the introduction of bone scans. These advanced methods allow tomographic image acquisition and help in attenuation correction with anatomical co-localization. The use of positron emission tomography/CT (PET/CT) scanners is also on the rise. These PET scanners are mainly utilized with 18F-sodium-fluoride (NaF), in order to visualize the skeleton and possible changes. Moreover, NaF PET/CT is associated with higher tracer uptake, increased target-to-background ratio and has a higher spatial resolution. However, these newer technologies have not been adopted in clinical guidelines due to lack of definite evidence in support of their use in bone metastases cases. The present review article is focused on current perspectives and challenges of computerized tomography (CT) applications in cases of bone metastases during prostate cancer.


2001 ◽  
Vol 95 (2) ◽  
pp. 292-297 ◽  
Author(s):  
Takeo Kondo ◽  
Toshihiro Kumabe ◽  
Shin Maruoka ◽  
Takashi Yoshimoto

Object. The 201Tl uptake index was evaluated for its usefulness in formulating a diagnosis of hemangioblastoma. Thallium-201—single-photon emission computerized tomography (SPECT) studies were performed in nine patients harboring hemangioblastomas in the posterior fossa and in five patients (six lesions) with gliomas in the posterior fossa. Methods. The 201Tl uptake index was defined as the ratio of mean counts of isotope per pixel in the tumor to mean counts of isotope per pixel in the homologous region of the healthy brain. The 201Tl uptake indices of the early image (TlE) and that of the delayed image (TlD) were calculated. The isotope retention index (RI) was calculated as (TlE − TlD)/TlE. The TlE was 2.7 ± 0.7 in hemangioblastomas and 2.9 ± 1.7 in gliomas (mean ± standard deviation). The TlD was 1.5 ± 0.4 in hemangioblastomas and 2.4 ± 1.6 in gliomas. There were no significant differences between hemangioblastomas and gliomas when TlEs and TlDs were compared. The isotope RI was 0.43 ± 0.07 in hemangioblastomas and 0.15 ± 0.1 in gliomas, showing a significantly higher RI in hemangioblastomas compared with gliomas (p < 0.01). Conclusions. Thallium-201 washout is significantly faster in hemangioblastomas. Hemangioblastoma is biologically benign, but contains a rich capillary network that forms a hypervascular tumor bed. Variations in its appearance on magnetic resonance images may cause difficulties in the differential diagnosis of hemangioblastoma. Thallium-201 SPECT studies can be used to distinguish hemangioblastomas from gliomas in the posterior fossa.


2003 ◽  
Vol 14 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Alberto Auricchio ◽  
Paul D. Acton ◽  
Markus Hildinger ◽  
Jean-Pierre Louboutin ◽  
Karl Plössl ◽  
...  

1987 ◽  
Vol 7 (1) ◽  
pp. 127-131 ◽  
Author(s):  
D. Perani ◽  
G. Lucignani ◽  
P. Pantano ◽  
P. Gerundini ◽  
G. L. Lenzi ◽  
...  

Regional cerebral and cerebellar blood flows were studied by N, N, N'-trimethyl- N'-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3-propanediamine 2 HC1 (1-123 HIPDM) and single-photon emission computerized tomography (SPECT) in a patient with an ischemic lesion of the pons. An asymmetry of perfusion of the cerebellar hemispheres, normal on transmission computerized tomography scan, was demonstrated by SPECT studies in the early acute phase and confirmed 15 days after. This finding may be related to the interruption of the corticopontocerebellar pathways.


1997 ◽  
Vol 92 (1) ◽  
pp. 81-85 ◽  
Author(s):  
David J. Ross ◽  
Pearl Wu ◽  
Zab Mohsenifar

1. With the advent of single-photon emission computerized tomography, controversy has arisen with regard to the significance of gravitational influences on regional pulmonary perfusion (Q̊r) in the supine versus prone postures. We investigated the dorsal—ventral distributions of Q̊r in prone (n = 5) and supine (n = 5) normal subjects, as assessed by single-photon emission computerized tomography after intravenous injection of technetium-99m-labelled macroaggregated albumin at end-tidal expiration. Reconstructed serial (one pixel thickness) coronal sections were traced on a computer screen, to yield the encompassed radioactive counts and number of pixels per each image. Coronal section data (expressed as mean radioactive counts/pixel) were expressed in a ‘profile’ and normalized to the maximum coronal section of each lung (%maximum). 2. Coefficients of variation and linear regression slopes for the prone versus supine profiles for left and right lungs were not statistically different (unpaired Student's t-test). The coronal section with maximum Q̊r was identified in the more dependent lung regions and, hence, affected by gravity. 3. We conclude that, in contrast to previous canine models, which have suggested postural differences in dorsal-ventral perfusion gradients, in normal man gravity primarily determines the non-dependent to dependent distribution of Q̊r. We speculate that interspecies differences in physiology may be teleological and related to the different perfusion demands of the quadruped compared with upright man.


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