Copper-64 labeled sulfophthalocyanines for positron emission tomography (PET) imaging in tumor-bearing rats

2008 ◽  
Vol 12 (01) ◽  
pp. 49-53 ◽  
Author(s):  
Anton Soucy-Faulkner ◽  
Jacques A. Rousseau ◽  
Réjean Langlois ◽  
Véronique Berard ◽  
Roger Lecomte ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Photodynamic Therapy ◽  
Emission Tomography ◽  
Tumor Uptake ◽  
Tissue Samples ◽  
Metal Free ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Tumor Selectivity

Sulfonated metallophthalocyanines ( PcS ) are second generation photosensitizers for photodynamic therapy (PDT) of cancer. Metal-free H 2 PcS are readily labeled with 64 Cu ++ to yield a mixture of sulfonated [64 Cu ] CuPcS suitable for biodistribution studies in tumor-bearing rats by positron emission tomography (PET). Most of the 64 Cu activity was sequestrated within the kidneys (20%ID/g) and liver (12%ID/g) while tumor uptake values remained low (0.2%ID/g). Dissection and counting of individual tissue samples after the 24 h scan confirmed the uptake values derived from the PET images. The procedure can be applied to series of novel PcS to evaluate structure-tumor selectivity relationships as a parameter to select potential agents for photodynamic therapy.

Dose Escalation Biodistribution, Positron Emission Tomography/Computed Tomography Imaging and Dosimetry of a Highly Specific Radionuclide-labeled Non-blocking Nanobody

2021 ◽  
Author(s):  
Yang yanling ◽  
Feng Zhao ◽  
Daquan Chen ◽  
Chao Wang ◽  
Yan Sun ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Nude Mice ◽  
Ex Vivo ◽  
Dose Range ◽  
Emission Tomography ◽  
Humanized Mice ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Pet Ct ◽  
Ex Vivo Biodistribution

Abstract Backgroud: Immunotherapy is a valuable option for the treatment of cancers, and the curative effect anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobodies. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, We explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by intravenous of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male using OLINDA2.1 software.Results: 68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPDL1 or MC38-hPDL1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3–100 µg in nude mice and approximately 1–100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3–10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15 μg/kg dose was adopted for the PET/CT imaging in cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, with the exception of the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injection of 185 MBq of 68Ga-NOTA-Nb109.Conclusion: 68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

scholarly journals Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marc C. Huisman ◽  
C. Willemien Menke-van der Houven van Oordt ◽  
Josée M. Zijlstra ◽  
Otto S. Hoekstra ◽  
Ronald Boellaard ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Positron Emission Tomography ◽  
Study Design ◽  
Future Study ◽  
False Positive ◽  
Emission Tomography ◽  
Tumor Uptake ◽  
Target Concentration ◽  
Positron Emission ◽  
Imaging Dose

Abstract Background 89Zirconium-immuno-positron emission tomography (89Zr-immuno-PET) is used for assessment of target status to guide antibody-based therapy. We aim to determine the relation between antibody tumor uptake and target concentration to improve future study design and interpretation. Methods The relation between tumor uptake and target concentration was predicted by mathematical modeling of 89Zr-labeled antibody disposition in the tumor. Literature values for trastuzumab kinetics were used to provide an example. Results 89Zr-trastuzumab uptake initially increases with increasing target concentration, until it levels off to a constant value. This is determined by the total administered mass dose of trastuzumab. For a commonly used imaging dose of 50 mg 89Zr-trastuzumab, uptake can discriminate between immunohistochemistry score (IHC) 0 versus 1–2–3. Conclusion The example for 89Zr-trastuzumab illustrates the potential to assess target expression. The pitfall of false-positive findings depends on the cut-off to define clinical target positivity (i.e., IHC 3) and the administered mass dose.

scholarly journals Selective radiolabelling with 68Ga under mild conditions: a route towards a porphyrin PET/PDT theranostic agent

2018 ◽  
Vol 54 (57) ◽  
pp. 7952-7954 ◽  
Author(s):  
Steven Y. Yap ◽  
Thomas W. Price ◽  
Huguette Savoie ◽  
Ross W. Boyle ◽  
Graeme J. Stasiuk
Keyword(s):  
Positron Emission Tomography ◽  
Photodynamic Therapy ◽  
Room Temperature ◽  
Emission Tomography ◽  
Mild Conditions ◽  
Theranostic Agent ◽  
Positron Emission

A theranostic porphyrin conjugate for use as a positron emission tomography (PET) radiotracer and as a photosensitiser for photodynamic therapy (PDT) has been synthesised. This conjugate can be radiolabelled with 68Ga at pH 7.4 at room temperature with an RCY of 80%.

scholarly journals Dose escalation biodistribution, positron emission tomography/computed tomography imaging and dosimetry of a highly specific radionuclide-labeled non-blocking nanobody

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanling Yang ◽  
Chao Wang ◽  
Yan Wang ◽  
Yan Sun ◽  
Xing Huang ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Nude Mice ◽  
Ex Vivo ◽  
Dose Range ◽  
Emission Tomography ◽  
Humanized Mice ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Pet Ct ◽  
Ex Vivo Biodistribution

Abstract Background Immunotherapy is a valuable option for cancer treatment, and the curative effect of anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobody. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, we explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by administration of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male and female using OLINDA2.1 software. Results 68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPD-L1 or MC38-hPD-L1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3–100 µg in nude mice and approximately 1–100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3–10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15-μg/kg dose was adopted for the PET/CT imaging in the cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, except the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injecting 185 MBq of 68Ga-NOTA-Nb109. Conclusion 68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

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