Development of radiolabeled mapatumumab and imaging in solid tumor patients who are treated with gemcitabine, cisplatin, and mapatumumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14521-e14521 ◽  
Author(s):  
C. Oldenhuis ◽  
E. C. Dijkers ◽  
E. W. Duiker ◽  
N. L. Fox ◽  
J. L. Klein ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Radiochemical Purity ◽  
Single Photon ◽  
Phase 1 ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Multiple Time ◽  
Tracer Injection ◽  
Camera Imaging

e14521 Background: Mapatumumab is a fully human agonistic monoclonal antibody (mAb) to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1). Mapatumumab combined with gemcitabine and cisplatin increased cytotoxicity in preclinical models and was safe in a phase 1 study. To study its biodistribution, 111Indium (111In) labeled mapatumumab was developed for γ-camera imaging and tested in mice. Subsequently, 111In-mapatumumab scintigraphy was performed in patients (pts). Methods: Mapatumumab was labeled with 111In. Labeling efficiency, radiochemical purity, stability and binding properties were determined in vitro. Biodistribution was studied at multiple time points in nude mice bearing human xenografts (SKBR3 or SW948). Tissue activity was expressed as % injected dose/gram tissue (%ID/g). In a feasibility study, gemcitabine 1250 mg/m2 IV on days 1 and 8, cisplatin 80 mg/m2 IV and mapatumumab 20 mg/kg on day 1 was administered to advanced solid tumor pts every 21 days. In cycles 1 and 3, pts underwent γ-camera imaging directly, and at day 1, 3, and 6 after 150 MBq 111In-mapatumumab IV (planar and single-photon emission computed tomography (SPECT)). Results: Labeling efficiency was 92.0% and radiochemical purity 96.0%. 111In-mapatumumab was stable in serum for 1 week at 37°C and specific TRAIL-R1 binding was maintained after labeling. In mice, high uptake was seen in liver (8.14 ± 0.75 %ID/g), kidneys (16.30 ± 1.75 %ID/g), spleen (7.25 ± 2.64 %ID/g) and bone (5.68 ± 1.31 %ID/g), with a maximum 24–72 hours (h) after tracer injection. Maximum uptake in the xenografts was observed after 72 h (7.55 ± 3.54 %ID/g for SKBR3 and 6.21 ± 2.03 %ID/g for SW948). Five pts have been enrolled in the ongoing clinical study. Known tumor lesions (by CT-scan) showed variable tracer uptake in 3 pts, while within pts not all known tumor lesions were positive on SPECT. Conclusions: Mapatumumab can be efficiently radiolabeled for clinical use. Preliminary results show that mapatumumab scintigraphy identifies some but not all tumor lesions in pts. This is the first demonstration that mAb targeting a TRAIL-R distributes to tumor tissues in patients and could potentially guide mapatumumab therapy. [Table: see text]

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 Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 918
Author(s):  
Marco Verona ◽  
Sara Rubagotti ◽  
Stefania Croci ◽  
Sophia Sarpaki ◽  
Francesca Borgna ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Single Photon ◽  
Photon Emission ◽  
Tumor Cell Line ◽  
Normal Tissues ◽  
Molar Activity ◽  
Suitable Target ◽  
Indium 111 ◽  
Preliminary Study

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [111In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.

Cardiac investigations: Nuclear, MRI, and CT

2020 ◽  
pp. 3326-3339
Author(s):  
Nikant Sabharwal ◽  
Andrew Kelion ◽  
Theodoros Karamitos ◽  
Stefan Neubauer
Keyword(s):  
Myocardial Perfusion ◽  
Single Photon ◽  
Photon Emission ◽  
Thallium 201 ◽  
Emission Computed Tomography ◽  
Tracer Injection ◽  
Single Photon Emission Computed ◽  
Anatomical Information ◽  
Photon Emission Computed Tomography

Myocardial perfusion scintigraphy provides physiological information about the coronary circulation, in contrast to the anatomical information provided by angiography. Three radionuclide-labelled perfusion tracers are routinely used in single photon emission computed tomography (SPECT) imaging: thallium-201 and the technetium-99m-labelled complexes sestamibi and tetrofosmin. Imaging is performed following tracer injection during stress (exercise or pharmacological) and at rest; comparison allows determination of whether regional perfusion is normal, or if there is inducible hypoperfusion or infarction/scar. Myocardial perfusion imaging is minimally invasive, and—in contrast to other methods of investigation—can be performed regardless of overall exercise capacity, abnormalities of the resting electrocardiogram, pacemakers, obesity, claustrophobia, renal dysfunction, iodine allergy, or acoustic windows.

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.

scholarly journals Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 182
Author(s):  
Ayman Abouzayed ◽  
Sara S. Rinne ◽  
Hamideh Sabahnoo ◽  
Jens Sörensen ◽  
Vladimir Chernov ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Computed Tomography ◽  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Absorbed Dose ◽  
Single Step ◽  
Emission Computed Tomography

Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.

scholarly journals Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 518
Author(s):  
Si’an Fang ◽  
Yuhao Jiang ◽  
Di Xiao ◽  
Xuran Zhang ◽  
Qianqian Gan ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Single Photon ◽  
Photon Emission ◽  
Sterile Inflammation ◽  
Imaging Agents ◽  
Emission Computed Tomography ◽  
Infection Imaging ◽  
Spect Image ◽  
Biodistribution Studies

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.

Cardiac investigation—nuclear and other imaging techniques

2010 ◽  
pp. 2670-2677
Author(s):  
Nikant Sabharwal ◽  
Andrew Kelion ◽  
Theo Karamitsos ◽  
Stefan Neubauer
Keyword(s):  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Thallium 201 ◽  
Emission Computed Tomography ◽  
Tracer Injection ◽  
Single Photon Emission Computed ◽  
Anatomical Information ◽  
Photon Emission Computed Tomography

Myocardial perfusion scintigraphy (MPS) provides physiological information about the coronary circulation, in contrast to the anatomical information provided by angiography. Three radionuclide-labelled perfusion tracers are routinely used in single photon emission computed tomography (SPECT) imaging: thallium-201 and the technetium-99 m-labelled complexes sestamibi and tetrofosmin. Imaging is performed following tracer injection during stress (exercise or pharmacological) and at rest; comparison allowing determination of whether regional perfusion is normal, or if there is inducible hypoperfusion or infarction/scar....

Sign in / Sign up

Export Citation Format

Share Document