scholarly journals Synthesis and Evaluation of 99mTc-Tricabonyl Labeled Isonitrile Conjugates for Prostate-Specific Membrane Antigen (PSMA) Image

Inorganics ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Nadeem Ahmed Lodhi ◽  
Ji Yong Park ◽  
Kyuwan Kim ◽  
Mi Kyung Hong ◽  
Young Joo Kim ◽  
...  
Keyword(s):  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Prostate Specific Membrane Antigen ◽  
Post Injection ◽  
Tumor Uptake ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA) is a biomarker expressed on the surface of prostate cancer (PCa). In an effort to improve the detection and treatment of PCa, small urea-based PSMA inhibitors have been studied extensively. In the present study, we aimed to develop 99mTc-tricabonyl labeled urea-based PSMA conjugates containing isonitrile (CN-R)-coordinating ligands ([99mTc]Tc-15 and [99mTc]Tc-16). Both the PSMA conjugates were obtained at high radiochemical efficiency (≥98.5%). High in vitro binding affinity was observed for [99mTc]Tc-15 and [99mTc]Tc-16 (Kd = 5.5 and 0.2 nM, respectively) in PSMA-expressing 22Rv1 cells. Tumor xenografts were conducted using 22Rv1 cells and rapid accumulation of [99mTc]Tc-16 (1.87 ± 0.11% ID/g) was observed at 1 h post-injection, which subsequently increased to (2.83 ± 0.26% ID/g) at 4 h post-injection. However, [99mTc]Tc-15 showed moderate tumor uptake (1.48 ± 0.18% ID/g), which decreased at 4 h post-injection (0.81 ± 0.09% ID/g). [99mTc]Tc-16 was excreted from non-targeted tissues with high tumor-to-blood (17:1) and tumor-to-muscle ratio (41:1) at 4 h post-injection at approximately 4 times higher levels than [99mTc]Tc-15. Uptakes of [99mTc]Tc-15 and [99mTc]Tc-16 to PSMA-expressing tumor and tissues were significantly blocked by co-injection of 2-(Phosphonomethyl)-pentandioic acid (2-PMPA), suggesting that their uptakes are mediated by PSMA specifically. Whole-body single photon emission computed tomography imaging of [99mTc]Tc-16 verified the ex vivo biodistribution results and demonstrated clear visualization of tumors and tissues expressing PSMA compared to [99mTc]Tc-15. In conclusion, using [99mTc]Tc-16 rather than [99mTc]Tc-15 may be the preferable because of its relatively high tumor uptake and retention.

scholarly journals Introduction to Infrared and Raman-Based Biomedical Molecular Imaging and Comparison with Other Modalities

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5547
Author(s):  
Carlos F. G. C. Geraldes
Keyword(s):  
Computed Tomography ◽  
Molecular Imaging ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Raman Imaging ◽  
Emission Computed Tomography ◽  
Label Free ◽  
Advantages And Disadvantages

Molecular imaging has rapidly developed to answer the need of image contrast in medical diagnostic imaging to go beyond morphological information to include functional differences in imaged tissues at the cellular and molecular levels. Vibrational (infrared (IR) and Raman) imaging has rapidly emerged among the molecular imaging modalities available, due to its label-free combination of high spatial resolution with chemical specificity. This article presents the physical basis of vibrational spectroscopy and imaging, followed by illustration of their preclinical in vitro applications in body fluids and cells, ex vivo tissues and in vivo small animals and ending with a brief discussion of their clinical translation. After comparing the advantages and disadvantages of IR/Raman imaging with the other main modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography/single-photon emission-computed tomography (PET/SPECT), ultrasound (US) and photoacoustic imaging (PAI), the design of multimodal probes combining vibrational imaging with other modalities is discussed, illustrated by some preclinical proof-of-concept examples.

Tc-99m labeled small-molecule inhibitors of prostate-specific membrane antigen (PSMA): New molecular imaging probes to detect metastatic prostate adenocarcinoma (PC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 173-173 ◽  
Author(s):  
Joseph Osborne ◽  
Naveed Hassan Akhtar ◽  
Shankar Vallabhajosula ◽  
Anastasia Nikolopoulou ◽  
Kevin P. Maresca ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Post Injection ◽  
Parotid Glands ◽  
Therapeutic Implications

173 Background: Sensitive and specific imaging remains a clinically-relevant problem for men with PC. PSMA is a well established target for imaging of PC with therapeutic implications. We have recently developed novel 99mTc-labeled small molecule inhibitors of the enzymatic domain of PSMA based on glutamate-urea-glutamate and glutamate-urea-lysine pharmacophores, and contain a bis-imidazole chelator to complex Tc-99m. Preclinical studies with PSMA positive LNCaP cells and xenografts demonstrate that 99mTc-MIP-1404 and 99mTc-MIP-1405 bind to PSMA with high affinity and localize in tumors rapidly. This study reports the first human data in men with metastatic PC and in healthy male subjects. Methods: Under an exploratory IND, using a cross-over design, the pharmacokinetics, biodistribution, and tumor uptake of 99mTc-MIP-1404 and 99mTc-MIP-1405 were compared in 6 healthy men and 6 men with radiographic evidence of metastatic PC. Whole body images were obtained at 10 min, 1, 2, 4 and 24 hr. Single photon emission computed tomography (SPECT) was performed between 3–4 hours post injection. Results: Both agents cleared the blood rapidly with MIP-1404 demonstrating significantly lower urinary activity (7%) compared to MIP-1405 (26%). Both agents showed persistent uptake in the salivary, lacrimal and parotid glands. Uptake in liver and kidney was acceptable for imaging at 1-2 hr post injection (PI). In men with PCa, both agents rapidly localized in bone and lymph node lesions as early as 1 hr PI. SPECT demonstrated excellent lesion contrast. Good correlation was seen with bone and CT scans, In majority of patients, more lesions including sub-cm lymph nodes were seen with 99mTc-MIP-1404 and 99mTc-MIP-1405. The high contrast images exhibited signal:noise ratios from 3:1 to 28:1 at 4 and 24 hr. Conclusions: 99mTc-MIP-1404 and 99mTc-MIP-1405 identified a greater number of lesions than bone scans and rapidly detected soft tissue PC lesions including sub-cm lymph nodes. Since 99mTc-MIP-1404 has minimal activity in the bladder, further work is planned to correlate imaging findings with histopathology in patients with high risk clinically-localized PC.

Improved techniques to localize foci of carcinoma within the prostate using high-resolution transrectal gamma imaging (TRGI) of monoclonal antibody directed at prostate specific membrane antigen (PSMA).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21026-e21026
Author(s):  
Benjamin L. Franc ◽  
Yonggang Cui ◽  
Seth A Rosenthal ◽  
Tammie Johnston ◽  
Uday Poonamallee ◽  
...  
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Subsequent Treatment ◽  
Tracer Uptake ◽  
Emission Computed Tomography ◽  
Prostate Specific Membrane Antigen ◽  
Signal Ratio ◽  
Gamma Imaging ◽  
Prostate Cancers ◽  
Specific Membrane

e21026 Background: As many as 40% of prostate cancers may be missed on biopsy, necessitating novel methods for biopsy guidance. There is also interest in mapping primary prostate cancers for treatment. The presented work evaluated the ability of a transrectal gamma-imaging (TRGI) device to detect and localize a prostate-specific membrane antigen (PSMA) - specific radiopharmaceutical in the prostate. Methods: The IRB approved this exploratory proof-of-concept study. Male patients with untreated, biopsy-proven prostatic adenocarcinoma received 5±0.5 mCi In-111 capromab pendetide (Prostascint, a PSMA-specific agent) i.v. and were imaged 4 days later using single photon emission computed tomography (SPECT-CT). A commercially available cadmium zinc telluride (CZT)-based endorectal gamma camera (ProxiScanTM, Hybridyne Imaging Technologies, Inc.) determined the radiopharmaceutical’s planar distribution (1.5x4 cm FOV; 5 min acquisition) in four prostatic quadrants. Safety assessments occurred day 1 and 7. MRI was acquired within 14 days. Pathology from TRUS biopsy or following prostatectomy identified prostatic quadrants containing adenocarcinoma. Results: Of 8 patients recruited, 6 completed imaging, all without adverse event. Subsequent treatment included prostatectomy (n=3) and radiation (n=3). Twenty-three prostatic quadrants were evaluated. In detecting a cancer-containing quadrant, TRGI, SPECT, and MRI had sensitivities of 100%, 75%, and 33%, respectively, and similar accuracy (61-70%). Target-to-background signal ratio of TRGI was independent of serum PSA level and not significantly different than SPECT. TRGI identified a greater number of foci in each quadrant when compared with SPECT (p<0.001). Lesion sizes on TRGI were smaller (p=0.04) and correlated with cancer size on pathology in patients treated surgically (r=0.69), identifying tracer uptake associated with tumors ≥ 5 mm. Conclusions: TRGI provides improved localization of prostate carcinoma compared with conventional SPECT with potential implications for the diagnosis and treatment of prostate cancer.

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 428
Author(s):  
Friederike Völter ◽  
Lena Mittlmeier ◽  
Astrid Gosewisch ◽  
Julia Brosch-Lenz ◽  
Franz Josef Gildehaus ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Biochemical Response ◽  
Emission Computed Tomography ◽  
Radioligand Therapy ◽  
Index Lesion ◽  
Recist 1.1 ◽  
Psma Pet

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

scholarly journals NIRF-Molecular Imaging with Synovial Macrophages-Targeting Vsig4 Nanobody for Disease Monitoring in a Mouse Model of Arthritis

2019 ◽  
Vol 20 (13) ◽  
pp. 3347 ◽  
Author(s):  
Fang Zheng ◽  
Siyu Luo ◽  
Zhenlin Ouyang ◽  
Jinhong Zhou ◽  
Huanye Mo ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Near Infrared ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Joint Inflammation ◽  
Experimental Arthritis ◽  
Emission Computed Tomography ◽  
Nirf Imaging

Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.

scholarly journals Tc-99m HYNIC-TOC scintigraphy in dedifferentiated thyroid cancer

2019 ◽  
Vol 12 (4) ◽  
pp. e227910
Author(s):  
Kanhaiyalal Agrawal ◽  
P Sai Sradha Patro ◽  
C Preetam
Keyword(s):  
Thyroid Cancer ◽  
Single Photon ◽  
Somatostatin Receptor ◽  
Photon Emission ◽  
Peptide Receptor Radionuclide Therapy ◽  
Ct Imaging ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Serum Thyroglobulin ◽  
Pet Ct

There is literature evidence showing utility of somatostatin receptor (SSTR) positron emission tomography-CT (PET-CT) imaging in differentiated thyroid cancer with Thyroglobulin Elevated and Negative Iodine Scan (TENIS). These patients are less benefited with I-131 therapy and surgery remains only curable option if disease could be localised. If surgery is not feasible, other therapeutic options are not promising. However, if these patients show strongly positive SSTR imaging, then possibility of peptide receptor radionuclide therapy may be explored. As SSTR PET-CT imaging is expensive and not widely available, Technetium-99m (Tc-99m) hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC), which is a Single photon emission computed tomography (SPECT) tracer, can be used. We are documenting a case of raised serum thyroglobulin antibody and negative I-131 whole body scan with disease recurrence localised on Tc-99m HYNIC-TOC scan.

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