Anncatrine Luisa Petersen - Academia.edu (original) (raw)

Papers by Anncatrine Luisa Petersen

Research paper thumbnail of 90-day survival from Gram negative sepsis according to disease severity

<b>Copyright information:</b>Taken from "Common TNF-α, IL-1β, PAI-1, uPA, CD14 a... more <b>Copyright information:</b>Taken from "Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis"http://www.biomedcentral.com/1471-2334/7/108BMC Infectious Diseases 2007;7():108-108.Published online 18 Sep 2007PMCID:PMC2034565. Log-rank test: P = 0.014.

Research paper thumbnail of Elucidating the anomalous membrane permeability of Ag(i), Cu(ii), Zn(ii) and Au(iii) towards new nanoreactor strategies for synthesizing metal nanoparticles

Nanoscale, 2020

The cations, Cu2+, Zn2+, Ag+and Au3+display anomalous membrane permeability, which is utilized fo... more The cations, Cu2+, Zn2+, Ag+and Au3+display anomalous membrane permeability, which is utilized for synthesis of gold nanoparticles inside liposomes.

Research paper thumbnail of Ladeverfahren für die zubereitung von radionuklid- und ioniophorhaltigen liposomen mit 2-hydroxychinolin (carbostyril) oder strukturverwandten 2-hydroxychinolinen als ionophor

Research paper thumbnail of Contribution of Nuclear Medicine to Cancer Nanotheranostics

Nanotheranostics for Personalized Medicine, 2016

Research paper thumbnail of Positron emission tomography evaluation of somatostatin receptor targeted 64Cu-TATE-liposomes in a human neuroendocrine carcinoma mouse model

Journal of Controlled Release, 2012

Targeted therapeutic and diagnostic nanocarriers functionalized with antibodies, peptides or othe... more Targeted therapeutic and diagnostic nanocarriers functionalized with antibodies, peptides or other targeting ligands that recognize over-expressed receptors or antigens on tumor cells have potential in the diagnosis and therapy of cancer. Somatostatin receptors (SSTRs) are over-expressed in a variety of cancers, particularly neuroendocrine tumors (NETs) and can be targeted with somatostatin peptide analogs such as octreotate (TATE). In the present study we investigate liposomes that target SSTR in a NET xenograft mouse model (NCI-H727) by use of TATE. TATE was covalently attached to the distal end of DSPE-PEG 2000 on PEGylated liposomes with an encapsulated positron emitter 64 Cu that can be utilized for positron emission tomography (PET) imaging. The biodistribution and pharmacokinetics of the 64 Cu-loaded PEGylated liposomes with and without TATE was investigated and their ability to image NETs was evaluated using PET. Additionally, the liposome accumulation and imaging capability was compared with free radiolabelled TATE peptide administered as 64 Cu-DOTA-TATE. The presence of TATE on the liposomes resulted in a significantly faster initial blood clearance in comparison to control-liposomes without TATE. PEGylated liposomes with or without TATE accumulated at significantly higher quantities in NETs (5.1 ± 0.3 and 5.8 ± 0.2 %ID/g, respectively) than the free peptide 64 Cu-DOTA-TATE (1.4 ± 0.3 %ID/g) 24 h post-injection. Importantly, 64 Cu-loaded PEGylated liposomes with TATE showed significantly higher tumor-to-muscle (T/M) ratio (12.7 ± 1.0) than the control-liposomes without TATE (8.9 ± 0.9) and the 64 Cu-DOTA-TATE free peptide (7.2 ± 0.3). The higher T/M ratio of the PEGylated liposomes with TATE suggests some advantage of active targeting of NETs, although no absolute benefit in tumor accumulation over the non-targeted liposomes was observed. Collectively, these data showed that 64 Cu-loaded PEGylated liposomes with TATE conjugated to the surface could be promising new imaging agents for visualizing tumor tissue and especially NETs using PET.

Research paper thumbnail of Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy: From material development to in vivo applications using positron emission tomography (PET) imaging

Research paper thumbnail of Technique De Chargement Pour Préparer Des Liposomes Contenant Des Radionucléide et Ionophores et Dans Lesquels L'Ionophore Est La 2-HYDROXYQUIONOLÉINE (Carbostyrile) Ou Des 2-HYDROXYQUINOLÉINES Structurellement Reliées

La presente invention concerne une nouvelle composition et un nouveau procede pour charger des sy... more La presente invention concerne une nouvelle composition et un nouveau procede pour charger des systemes d'administration, tels que des compositions de liposomes, avec des radionucleides utiles dans le diagnostic cible et/ou la therapie ciblee d'un site cible, tel qu'un tissu cancereux et, de maniere generale, des etats pathologiques associes a des vaisseaux sanguins fuyants. La composition et les procedes selon l'invention trouvent une utilisation particuliere dans le diagnostic et l'imagerie de tissus cancereux et, de maniere generale, d'etats pathologiques associes a des vaisseaux sanguins fuyants chez un sujet. La presente invention concerne egalement un nouvel outil de diagnostic pour l'utilisation d'une technique d'imagerie par tomographie par emission de positons (PET). Un aspect particulier de l'invention concerne un procede de production de nanoparticules avec des proprietes de ciblage desirees pour des applications de diagnostic et/ou de radiotherapie.

Research paper thumbnail of BMC Infectious Diseases BioMed Central

CiteSeerX - Document Details (Isaac Councill, Lee Giles): Research article Immune responses in pa... more CiteSeerX - Document Details (Isaac Councill, Lee Giles): Research article Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine.

Research paper thumbnail of Liposome imaging agents in personalized medicine

Advanced Drug Delivery Reviews, 2012

In recent years the importance of molecular and diagnostic imaging has increased dramatically in ... more In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been an important tool in the development of liposomal drugs. However, advanced imaging systems now provide new possibilities for non-invasive monitoring of liposome biodistribution in humans. Thus, advances in imaging and developments in liposome radiolabeling techniques allow us to enter a new arena where we start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development of radiolabeled liposomes for imaging as a tool in personalized medicine.

Research paper thumbnail of 64Cu loaded liposomes as positron emission tomography imaging agents

Biomaterials, 2011

We have developed a highly efficient method for utilizing liposomes as imaging agents for positro... more We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclide (64 Cu) using a new ionophore, 2-hydroxyquinoline, to carry 64 Cu(II) across the membrane of preformed liposomes and deliver it to an encapsulated copper-chelator. Using this ionophore we achieved very efficient loading (95.5 AE 1.6%) and retention stability (>99%), which makes the 64 Cu-liposomes highly applicable as PET imaging agents. We show the utility of the 64 Cu-liposomes for quantitative in vivo imaging of healthy and tumor-bearing mice using PET. This remote loading method is a powerful tool for characterizing the in vivo performance of liposome based nanomedicine, and has great potential in diagnostic and therapeutic applications.

Research paper thumbnail of Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

BMC Infectious Diseases, 2007

Background Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate ... more Background Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population. Methods Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-α, (TNF-α), interleukin-1β (IL-1β), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14 and toll-like receptor 4 (TLR4) was done. Results Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-α, IL-1β, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hos...

Research paper thumbnail of Stereotactic Body Radiation Therapy (SBRT) for lung metastases

Research paper thumbnail of Entrapment of Radionuclides in Nanoparticle Compositions

Research paper thumbnail of Loading technique for preparing radionuclide and ionophore containing liposomes in which the ionophore is 2-hydroxyquionoline (carbostyril) or structurally related 2-hydroxyquinolines

Research paper thumbnail of In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

European Journal of Nuclear Medicine and Molecular Imaging, 2015

 Users may download and print one copy of any publication from the public portal for the purpose... more  Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Research paper thumbnail of Remote Loading of 64 Cu 2+ into Liposomes without use of Ion Transport Enhancers

ACS Applied Materials & Interfaces, 2015

Due to low ion permeability of lipid bilayers, it has been and still is common practice to use tr... more Due to low ion permeability of lipid bilayers, it has been and still is common practice to use transporter molecules such as ionophores or lipophilic chelators to increase trans-membrane diffusion rates and loading efficiencies of radionuclides into liposomes. Here, we report a novel and very simple method for loading the positron emitter 64 Cu 2+ into liposomes, which is important for in vivo positron emission tomography (PET) imaging. By this approach, copper is added to liposomes entrapping a chelator, which causes spontaneous diffusion of copper across the lipid bilayer where it is trapped. Using this method, we achieve highly efficient 64 Cu 2+ loading, high radionuclide retention, and favorable loading kinetics, excluding use of transporter molecule additives. We investigate the molecular coordination of entrapped copper using X-ray absorption spectroscopy, and demonstrate high adaptability of the loading method to different lipid formulations. We demonstrate high in vivo stability of 64 Cu-liposomes in a canine cancer model and evaluate tumor accumulation in mice using PET imaging. With this work, it is demonstrated that copper ions are capable of crossing a lipid membrane unassisted. This method is highly valuable for characterizing in vivo performance of liposome-based nanomedicine with great potential in diagnostic imaging applications.

Research paper thumbnail of Positron Emission Tomography based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer using Copper-64 Liposomes

ACS nano, Jan 29, 2015

Since the first report of the enhanced permeability and retention (EPR) effect, the research in n... more Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based anti-tumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years was considered to be a ubiquitous phenomenon. However, the understanding of differences in the EPR-effect between tumor types, heterogeneities within each patient group, and dependency on tumor development stage in humans is sparse. It is therefore important to enhance our understanding of the EPR-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide the first high-resolution analysis of EPR-based tumor accumulation in large animals. We find ...

Research paper thumbnail of Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases

International Journal of Radiation Oncology*Biology*Physics, 2007

Background: Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as mono... more Background: Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods: Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35-36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. Results: All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/ obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions: In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration: The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009-510).

Research paper thumbnail of 90-day survival from Gram negative sepsis according to disease severity

<b>Copyright information:</b>Taken from "Common TNF-α, IL-1β, PAI-1, uPA, CD14 a... more <b>Copyright information:</b>Taken from "Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis"http://www.biomedcentral.com/1471-2334/7/108BMC Infectious Diseases 2007;7():108-108.Published online 18 Sep 2007PMCID:PMC2034565. Log-rank test: P = 0.014.

Research paper thumbnail of Elucidating the anomalous membrane permeability of Ag(i), Cu(ii), Zn(ii) and Au(iii) towards new nanoreactor strategies for synthesizing metal nanoparticles

Nanoscale, 2020

The cations, Cu2+, Zn2+, Ag+and Au3+display anomalous membrane permeability, which is utilized fo... more The cations, Cu2+, Zn2+, Ag+and Au3+display anomalous membrane permeability, which is utilized for synthesis of gold nanoparticles inside liposomes.

Research paper thumbnail of Ladeverfahren für die zubereitung von radionuklid- und ioniophorhaltigen liposomen mit 2-hydroxychinolin (carbostyril) oder strukturverwandten 2-hydroxychinolinen als ionophor

Research paper thumbnail of Contribution of Nuclear Medicine to Cancer Nanotheranostics

Nanotheranostics for Personalized Medicine, 2016

Research paper thumbnail of Positron emission tomography evaluation of somatostatin receptor targeted 64Cu-TATE-liposomes in a human neuroendocrine carcinoma mouse model

Journal of Controlled Release, 2012

Targeted therapeutic and diagnostic nanocarriers functionalized with antibodies, peptides or othe... more Targeted therapeutic and diagnostic nanocarriers functionalized with antibodies, peptides or other targeting ligands that recognize over-expressed receptors or antigens on tumor cells have potential in the diagnosis and therapy of cancer. Somatostatin receptors (SSTRs) are over-expressed in a variety of cancers, particularly neuroendocrine tumors (NETs) and can be targeted with somatostatin peptide analogs such as octreotate (TATE). In the present study we investigate liposomes that target SSTR in a NET xenograft mouse model (NCI-H727) by use of TATE. TATE was covalently attached to the distal end of DSPE-PEG 2000 on PEGylated liposomes with an encapsulated positron emitter 64 Cu that can be utilized for positron emission tomography (PET) imaging. The biodistribution and pharmacokinetics of the 64 Cu-loaded PEGylated liposomes with and without TATE was investigated and their ability to image NETs was evaluated using PET. Additionally, the liposome accumulation and imaging capability was compared with free radiolabelled TATE peptide administered as 64 Cu-DOTA-TATE. The presence of TATE on the liposomes resulted in a significantly faster initial blood clearance in comparison to control-liposomes without TATE. PEGylated liposomes with or without TATE accumulated at significantly higher quantities in NETs (5.1 ± 0.3 and 5.8 ± 0.2 %ID/g, respectively) than the free peptide 64 Cu-DOTA-TATE (1.4 ± 0.3 %ID/g) 24 h post-injection. Importantly, 64 Cu-loaded PEGylated liposomes with TATE showed significantly higher tumor-to-muscle (T/M) ratio (12.7 ± 1.0) than the control-liposomes without TATE (8.9 ± 0.9) and the 64 Cu-DOTA-TATE free peptide (7.2 ± 0.3). The higher T/M ratio of the PEGylated liposomes with TATE suggests some advantage of active targeting of NETs, although no absolute benefit in tumor accumulation over the non-targeted liposomes was observed. Collectively, these data showed that 64 Cu-loaded PEGylated liposomes with TATE conjugated to the surface could be promising new imaging agents for visualizing tumor tissue and especially NETs using PET.

Research paper thumbnail of Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy: From material development to in vivo applications using positron emission tomography (PET) imaging

Research paper thumbnail of Technique De Chargement Pour Préparer Des Liposomes Contenant Des Radionucléide et Ionophores et Dans Lesquels L'Ionophore Est La 2-HYDROXYQUIONOLÉINE (Carbostyrile) Ou Des 2-HYDROXYQUINOLÉINES Structurellement Reliées

La presente invention concerne une nouvelle composition et un nouveau procede pour charger des sy... more La presente invention concerne une nouvelle composition et un nouveau procede pour charger des systemes d'administration, tels que des compositions de liposomes, avec des radionucleides utiles dans le diagnostic cible et/ou la therapie ciblee d'un site cible, tel qu'un tissu cancereux et, de maniere generale, des etats pathologiques associes a des vaisseaux sanguins fuyants. La composition et les procedes selon l'invention trouvent une utilisation particuliere dans le diagnostic et l'imagerie de tissus cancereux et, de maniere generale, d'etats pathologiques associes a des vaisseaux sanguins fuyants chez un sujet. La presente invention concerne egalement un nouvel outil de diagnostic pour l'utilisation d'une technique d'imagerie par tomographie par emission de positons (PET). Un aspect particulier de l'invention concerne un procede de production de nanoparticules avec des proprietes de ciblage desirees pour des applications de diagnostic et/ou de radiotherapie.

Research paper thumbnail of BMC Infectious Diseases BioMed Central

CiteSeerX - Document Details (Isaac Councill, Lee Giles): Research article Immune responses in pa... more CiteSeerX - Document Details (Isaac Councill, Lee Giles): Research article Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine.

Research paper thumbnail of Liposome imaging agents in personalized medicine

Advanced Drug Delivery Reviews, 2012

In recent years the importance of molecular and diagnostic imaging has increased dramatically in ... more In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been an important tool in the development of liposomal drugs. However, advanced imaging systems now provide new possibilities for non-invasive monitoring of liposome biodistribution in humans. Thus, advances in imaging and developments in liposome radiolabeling techniques allow us to enter a new arena where we start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development of radiolabeled liposomes for imaging as a tool in personalized medicine.

Research paper thumbnail of 64Cu loaded liposomes as positron emission tomography imaging agents

Biomaterials, 2011

We have developed a highly efficient method for utilizing liposomes as imaging agents for positro... more We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclide (64 Cu) using a new ionophore, 2-hydroxyquinoline, to carry 64 Cu(II) across the membrane of preformed liposomes and deliver it to an encapsulated copper-chelator. Using this ionophore we achieved very efficient loading (95.5 AE 1.6%) and retention stability (>99%), which makes the 64 Cu-liposomes highly applicable as PET imaging agents. We show the utility of the 64 Cu-liposomes for quantitative in vivo imaging of healthy and tumor-bearing mice using PET. This remote loading method is a powerful tool for characterizing the in vivo performance of liposome based nanomedicine, and has great potential in diagnostic and therapeutic applications.

Research paper thumbnail of Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

BMC Infectious Diseases, 2007

Background Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate ... more Background Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population. Methods Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-α, (TNF-α), interleukin-1β (IL-1β), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14 and toll-like receptor 4 (TLR4) was done. Results Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-α, IL-1β, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hos...

Research paper thumbnail of Stereotactic Body Radiation Therapy (SBRT) for lung metastases

Research paper thumbnail of Entrapment of Radionuclides in Nanoparticle Compositions

Research paper thumbnail of Loading technique for preparing radionuclide and ionophore containing liposomes in which the ionophore is 2-hydroxyquionoline (carbostyril) or structurally related 2-hydroxyquinolines

Research paper thumbnail of In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

European Journal of Nuclear Medicine and Molecular Imaging, 2015

 Users may download and print one copy of any publication from the public portal for the purpose... more  Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Research paper thumbnail of Remote Loading of 64 Cu 2+ into Liposomes without use of Ion Transport Enhancers

ACS Applied Materials & Interfaces, 2015

Due to low ion permeability of lipid bilayers, it has been and still is common practice to use tr... more Due to low ion permeability of lipid bilayers, it has been and still is common practice to use transporter molecules such as ionophores or lipophilic chelators to increase trans-membrane diffusion rates and loading efficiencies of radionuclides into liposomes. Here, we report a novel and very simple method for loading the positron emitter 64 Cu 2+ into liposomes, which is important for in vivo positron emission tomography (PET) imaging. By this approach, copper is added to liposomes entrapping a chelator, which causes spontaneous diffusion of copper across the lipid bilayer where it is trapped. Using this method, we achieve highly efficient 64 Cu 2+ loading, high radionuclide retention, and favorable loading kinetics, excluding use of transporter molecule additives. We investigate the molecular coordination of entrapped copper using X-ray absorption spectroscopy, and demonstrate high adaptability of the loading method to different lipid formulations. We demonstrate high in vivo stability of 64 Cu-liposomes in a canine cancer model and evaluate tumor accumulation in mice using PET imaging. With this work, it is demonstrated that copper ions are capable of crossing a lipid membrane unassisted. This method is highly valuable for characterizing in vivo performance of liposome-based nanomedicine with great potential in diagnostic imaging applications.

Research paper thumbnail of Positron Emission Tomography based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer using Copper-64 Liposomes

ACS nano, Jan 29, 2015

Since the first report of the enhanced permeability and retention (EPR) effect, the research in n... more Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based anti-tumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years was considered to be a ubiquitous phenomenon. However, the understanding of differences in the EPR-effect between tumor types, heterogeneities within each patient group, and dependency on tumor development stage in humans is sparse. It is therefore important to enhance our understanding of the EPR-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide the first high-resolution analysis of EPR-based tumor accumulation in large animals. We find ...

Research paper thumbnail of Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases

International Journal of Radiation Oncology*Biology*Physics, 2007

Background: Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as mono... more Background: Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods: Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35-36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. Results: All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/ obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions: In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration: The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009-510).