[<Superscript>89</Superscript>Zr]Trastuzumab: Evaluation of Radiation Dosimetry,Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer

Purpose

The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [⁸⁹Zr]trastuzumab in patients with HER2-positive breast cancer.

Procedures

Twelve women with HER2-positive breast cancer underwent [⁸⁹Zr]trastuzumab positron emission tomography (PET)/X-ray computed tomography (CT) twice within 7 days post-injection. Biodistribution data from whole-torso PET/CT images and organ time-activity curves were created using data from all patients. Human dosimetry was calculated using OLINDA with the adult female model.

Results

High-quality images and the greatest tumor-to-nontumor contrast were achieved with images performed 5?±?1 day post-injection. Increased [⁸⁹Zr]trastuzumab uptake was seen in at least one known lesion in ten patients. The liver was the dose-limiting organ (retention of ～12 % of the injected dose and average dose of 1.54 mSv/MBq). The effective dose was 0.47 mSv/MBq. No adverse effects of [⁸⁹Zr]trastuzumab were encountered.

Conclusion

[⁸⁹Zr]trastuzumab was safe and optimally imaged at least 4 days post-injection. The liver was the dose-limiting organ.

     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Comparison of Selected Ga-68 and Zr-89 Labelled Siderophores

Purpose

Some [⁶⁸Ga]siderophores show promise in specific and sensitive imaging of infection. Here, we compare the in vitro and in vivo behaviour of selected Ga-68 and Zr-89 labelled siderophores.

Procedures

Radiolabelling was performed in HEPES or sodium acetate buffer systems. Radiochemical purity of labelled siderophores was determined using chromatography. Partition coefficients, in vitro stability and protein binding affinities were determined. Ex vivo biodistribution and animal imaging was studied in mice.

Results

Certain differences among studied siderophores were observed in labelling efficiency. Protein binding and stability tests showed highest stabilities and lowest protein binding affinities for Ga-68 and [⁸⁹Zr]triacetylfusarinine C (TAFC). All studied Ga-68 and [⁸⁹Zr]siderophores exhibited a similar biodistribution and pharmacokinetics in mice with the exception of [⁸⁹Zr]ferrioxamine E (FOXE).

Conclusions

Zr-89 and [⁶⁸Ga]siderophores showed analogous in vitro and in vivo behaviour. Tested [⁸⁹Zr]siderophores could be applied for longitudinal positron emission tomography (PET) studies of fungal infections and especially TAFC for the development of novel bioconjugates.

     

Strain Differences Determine the Suitability of Animal Models for Noninvasive <Emphasis Type="Italic">In Vivo</Emphasis> Beta Cell Mass Determination with Radiolabeled Exendin

Purpose

Noninvasive beta cell mass (BCM) quantification is a crucial tool to understand diabetes development and progression. [¹¹¹In]exendin is a promising agent for in vivo beta cell imaging, but tracer testing has been hampered by the lack of well-defined rodent models.

Procedures

Biodistribution and pancreatic uptake of [¹¹¹In]exendin were compared in rats and mice. In selected models, the amount of [¹¹¹In]exendin accumulation in the pancreas and other organs was determined using a model of alloxan-induced beta cell loss. GLP-1R expression levels were analyzed by RT-PCR and immunohistochemistry.

Results

Namely Brown Norway rats showed beta-cell-specific tracer accumulation and favorable pancreas-to-background ratios for noninvasive BCM determination. Mice displayed receptor-mediated [¹¹¹In]exendin uptake in endocrine and exocrine pancreas, in spite of very low GLP-1R expression in exocrine tissue.

Conclusions

Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans.

     

Tumor-Specific Zr-89 Immuno-PET Imaging in a Human Bladder Cancer Model

Purpose

Tumor-specific molecular imaging is an important tool for assessing disease burden and treatment response. CA19.9 is an important tumor-specific marker in several malignancies, including urothelial carcinoma. [⁸⁹Zr]DFO-HuMab-5B1 (MVT-2163) is a CA19.9-specific antibody-based construct that has been validated in preclinical animal models of lung, colorectal, and pancreatic malignancies for positron emission tomography (PET) imaging and is currently in a phase I trial for pancreatic cancer (NCT02687230). Here, we examine whether [⁸⁹Zr]DFO-HuMab-5B1 may be useful in defining urothelial malignancies.

Procedures

Surface expression of CA19.9 was confirmed in the human bladder cancer line HT 1197. The radioimmunoconjugate [⁸⁹Zr]DFO-HuMab-5B1 was injected into mice bearing HT 1197 xenografts, and followed by PET imaging, ex vivo experiments including biodistribution, histology and autoradiography, and analysis of blood samples for shed antigen levels were performed.

Results

[⁸⁹Zr]DFO-HuMab-5B1 specifically accumulates in HT 1197 engrafted tumors when imaged with PET. Ex vivo biodistribution of organs and autoradiography of engrafted tumors confirm our construct’s specific tumor binding. The target antigen CA19.9 was not found to be shed in vitro or in vivo.

Conclusions

[⁸⁹Zr]DFO-HuMab-5B1 can be used to delineate urothelial carcinomas by PET imaging and may provide tumor-specific information prior to, during, and after systemic therapies.

     

CD80 Is Upregulated in a Mouse Model with Shear Stress-Induced Atherosclerosis and Allows for Evaluating CD80-Targeting PET Tracers

Purpose

A shear stress-induced atherosclerosis mouse model was characterized for its expression of inflammation markers with focus on CD80. With this model, we evaluated two positron emission tomography (PET) radiotracers targeting CD80 as well as 2-deoxy-2-[¹⁸F]fluoro-d-mannose ([¹⁸F]FDM) in comparison with 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG).

Procedure

A flow constrictive cuff implanted around the common carotid artery in apolipoprotein E knockout mice resulted in plaque formation. CD80 expression levels and plaque histopathology were evaluated. Serial PET/X-ray computed tomography scans were performed to follow inflammation.

Results

Plaque formation with increased levels of CD80 was observed. Histologically, plaques presented macrophage-rich and large necrotic areas covered by a thin fibrous cap. Of the CD80-specific tracers, one displayed an increased uptake in plaques by PET. Both [¹⁸F]FDG and [¹⁸F]FDM accumulated in atherosclerotic plaques.

Conclusion

This mouse model presented, similar to humans, an increased expression of CD80 which renders it suitable for non-invasively targeting CD80-positive immune cells and evaluating CD80-specific radiotracers.

     

PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis

Purpose

Upregulation of sphingosine-1-phosphate receptor 1 (S1PR1) expression in multiple sclerosis (MS) lesions is associated with neuroinflammatory response. This study investigated the correlation between neuroinflammation and S1PR1 expression in the spinal cord of an experimental autoimmune encephalomyelitis (EAE) rat model of MS, using the S1PR1 positron emission tomography (PET) radiotracer [¹¹C]TZ3321.

Procedures

MicroPET imaging studies of [¹¹C]TZ3321 were performed to measure uptake of [¹¹C]TZ3321 in the spinal cord of EAE rats. Immunohistochemical staining was performed to confirm the overexpression of S1PR1 and other inflammatory biomarkers.

Results

MicroPET imaging demonstrated a 20–30 % increase in [¹¹C]TZ3321 uptake in the lumbar spinal cord of EAE rats versus sham controls at 35–60 min post injection. The increased uptake of [¹¹C]TZ3321 was correlated with the overexpression of S1PR1 in the lumbar spinal cord of EAE rats that was confirmed by immunohistochemical staining. Upregulated S1PR1 expression was associated with glial cell activation and immune cell infiltration.

Conclusions

MicroPET imaging modality with a specific radioligand [¹¹C]TZ3321 is able to assess the expression of S1PR1 in EAE rat lumbar spinal cord. This may provide a new approach to the assessment of neuroinflammatory response in MS and other inflammatory diseases.

     

Repeatability of Radiomic Features in Non-Small-Cell Lung Cancer [<Superscript>18</Superscript>F]FDG-PET/CT Studies: Impact of Reconstruction and Delineation

Purpose

To assess (1) the repeatability and (2) the impact of reconstruction methods and delineation on the repeatability of 105 radiomic features in non-small-cell lung cancer (NSCLC) 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomorgraphy/computed tomography (PET/CT) studies.

Procedures

Eleven NSCLC patients received two baseline whole-body PET/CT scans. Each scan was reconstructed twice, once using the point spread function (PSF) and once complying with the European Association for Nuclear Medicine (EANM) guidelines for tumor PET imaging. Volumes of interest (n?=?19) were delineated twice, once on PET and once on CT images.

Results

Sixty-three features showed an intraclass correlation coefficient?≥?0.90 independent of delineation or reconstruction. More features were sensitive to a change in delineation than to a change in reconstruction (25 and 3 features, respectively).

Conclusions

The majority of features in NSCLC [¹⁸F]FDG-PET/CT studies show a high level of repeatability that is similar or better compared to simple standardized uptake value measures.

     

Synthesis and Evaluation of a Zr-89-Labeled Monoclonal Antibody for Immuno-PET Imaging of Amyloid-β Deposition in the Brain

Purpose

The aim of this study was to evaluate the in vitro and in vivo characteristics of [⁸⁹Zr]JRF/AβN/25, a radiolabeled monoclonal antibody directed against amyloid-β (Aβ).

Procedures

JRF/AβN/25 was labeled with ⁸⁹Zr following modification with desferal. The affinity of the tracer for Aβ_1–40 was determined in a saturation binding assay. In vitro stability was evaluated, and in vivo plasma stability and biodistribution of [⁸⁹Zr]Df-Bz-JRF/AβN/25 were determined in wild-type mice. To evaluate whether the antibody can cross the blood-brain barrier, brain uptake in wild-type mice was additionally assessed by ex vivo autoradiography.

Results

[⁸⁹Zr]Df-Bz-JRF/AβN/25 was obtained in an average radiochemical yield of 50 % and a radiochemical purity of >97 %. A saturation binding assay demonstrated specific binding of [⁸⁹Zr]Df-Bz-JRF/AβN/25 to Aβ_1–40 with nanomolar affinity. The tracer was stable in buffer and proved to be stable in vivo with >92 % intact monoclonal antibody (mAb) remaining in the plasma at 48 h post injection. A biodistribution study showed a slow blood clearance with no significant accumulation of activity in any of the organs. Furthermore, [⁸⁹Zr]Df-Bz-JRF/AβN/25 demonstrated modest brain penetration, which slowly decreased in time. This cerebral uptake was confirmed by ex vivo autoradiography.

Conclusions

[⁸⁹Zr]Df-Bz-JRF/AβN/25 binds with high affinity to Aβ_1–40. The tracer displays an acceptable in vivo stability and is able to cross the blood-brain barrier. [⁸⁹Zr]Df-Bz-JRF/AβN/25 might therefore be a potential candidate for in vivo imaging of Aβ deposition in the brain.

     

Evaluation of Quantitative Imaging Biomarkers in the DSS Colitis Model

Purpose

In humans, colonoscopy is the gold standard for the diagnosis of inflammatory changes of the colon wall. Aim of this study was the identification of less invasive imaging biomarkers in the dextran sodium sulfate (DSS) colitis model to provide additional information on transmural changes of the colon wall.

Procedures

Colitis was induced in C57BL/6 mice by administration of 2, 3, and 4 % DSS over a period of 5 days. Colon wall thickness was measured using magnetic resonance imaging (MRI), ultrasound (US), and x-ray computed tomography (CT), gut inflammation by positron emission tomography/CT, and mucosal changes of the colon wall by colonoscopy. Colon samples were examined histologically.

Results

MRI, CT, US, and histological data revealed increased colon wall thickness in DSS-treated mice compared to healthy controls. Elevated 2-deoxy-2[¹⁸F]fluoro-d-glucose uptake and colonoscopy confirmed high inflammatory load in the guts of colitis mice.

Conclusions

The established quantitative imaging readouts offer promising perspectives to develop new compounds and to translate these methods into the clinical setting.

     

Imaging CXCR4 Expression with <Superscript>99m</Superscript>Tc-Radiolabeled Small-Interference RNA in Experimental Human Breast Cancer Xenografts

Purpose

Noninvasive quantification of chemokine receptor 4 (CXCR4) expression could serve as a prognostic indicator and may be of value for the design of personalized therapies and posttreatment monitoring. The objective of the present study was to assess the use of ^99mTc-radiolabeled small-interference RNA (siRNA) targeting CXCR4 to detect CXCR4 expression in vivo.

Procedures

CXCR4 siRNAs were radiolabeled with ^99mTc using the bifunctional chelator hydrazinonicotinamide (HYNIC), and the labeling efficiency, specific activity and radiochemical purity were determined. The stability of the probe in serum was assessed by measuring its radiochemical purity and inhibitory activity by RT-PCR and western blotting. Biodistribution studies and static imaging were performed in MDA-MB-231 tumor-bearing mice.

Results

Radiochemical purity remained highly stable in PBS and fresh human serum at room temperature and at 37 °C. Radiolabeled siRNA1 showed strong inhibitory effects similar to those of unlabeled siRNA1 on both CXCR4 messenger RNA (mRNA) and protein in vitro. The excretion of the probe occurred mainly through the liver and kidneys. Tumors were clearly visualized at 1–10 h after injection of the probe, but not after injection of the control probe.

Conclusions

^99mTc-labeled CXCR4 siRNA1 shows tumor-specific accumulation and could be a promising strategy for the visualization of CXCR4 expression in human breast cancer.

     

Reference ranges for rotational thromboelastometry in male Sprague Dawley rats

Background

A functional coagulation assay was used to investigate the extrinsic pathway of coagulation on citrated whole blood samples from healthy adult male Sprague Dawley rats using the mini cup and pin system.

Methods

Reference values for coagulation parameters from forty-three animals were calculated using data obtained from the ROTEM® delta hemostasis analyzer with the EXTEM test.

Results

The following ranges, presented as the 2.5–97.5 percentiles, were established: CT [18–77], CFT [20–80], α [73–86], MCF [53–70], and ML [1–22], along with others.

Conclusions

These reference ranges can be used in future studies in rats to identify clinically significant coagulopathies.

     

Preclinical Evaluation of 4-[<Superscript>18</Superscript>F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer

Purpose

Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[¹⁸F]Fluoroglutamine (4-[¹⁸F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression.

Procedures

In vivo microPET studies of 4-[¹⁸F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting.

Result

4-[¹⁸F]Fluoro-Gln uptake, but not 2-deoxy-2-[¹⁸F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[¹⁸F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues.

Conclusions

4-[¹⁸F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.

     

Biodistribution and Radiation Dosimetry of [<Superscript>18</Superscript>F]Mefway in Humans

Purpose

[¹⁸F]Mefway is a positron emission tomography (PET) radioligand for quantification of the brain serotonin 1A (5-HT_1A) receptor density. The purpose of this study was to evaluate the radiation safety of [¹⁸F]Mefway in humans.

Procedures

Six healthy volunteers (three males and three females) were whole-body PET scanned for 114 min after injection of [¹⁸F]Mefway (226?±?35 MBq). Estimated radiation doses were determined by the OLINDA/EXM software.

Results

[¹⁸F]Mefway was safe and well tolerated by all subjects. Residence time ranges from 0 (gallbladder) to 0.822 h (urinary bladder wall). While the estimated radiation doses in the reproductive and blood-forming organs were below 13.35–22.87 μSv/MBq, radiation dose in the urinary bladder wall was 471 μSv/MBq. The mean effective dose was 40.23?±?6.63 μSv/MBq.

Conclusion

For a typical single injection of 185 MBq (5 mCi), the dose will result in 87.1 mSv for the urinary bladder wall. To reduce radiation burden, the bladder voiding can be used before [¹⁸F]Mefway PET scan.

     

Al[<Superscript>18</Superscript>F]NOTA-T140 Peptide for Noninvasive Visualization of CXCR4 Expression

Purpose

Chemokine receptor CXCR4 plays an important role in tumor aggressiveness, invasiveness, and metastasis formation. Quantification of CXCR4 expression by tumors may have an impact on prediction and evaluation of tumor response to therapies. In this study, we developed a robust and straightforward F-18 labeling route of T140, a CXCR4 peptide-based antagonist.

Procedures

T140 derivative was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and labeled with Al[¹⁸F]. Al[¹⁸F]NOTA-T140 was evaluated in vitro in cell-based assay and stability in mouse serum and in vivo using CXCR4 positive and negative tumor xenograft models.

Results

Labeling of Al[¹⁸F]NOTA-T140 was completed within 30 min with a radiochemical yield of 58?±?5.3 % at the end of synthesis, based on fluoride-18 activity. Al[¹⁸F]NOTA-T140 accumulated in CHO-CXCR4 positive but not negative tumors. Al[¹⁸F]NOTA-T140 uptake in the tumors correlated with CXCR4 protein expression. Moreover, Al[¹⁸F]NOTA-T140 had high accumulation in CXCR4-positive metastatic tumors.

Conclusions

The simplicity of Al[¹⁸F]NOTA-T140 labeling along with its properties to specifically image CXCR4 expression by tumors warrant further clinical application for the diagnosis of CXCR4 clinically.

     

Biodistribution and Radiation Dosimetry of the <Emphasis Type="Italic">Enterobacteriaceae</Emphasis>-Specific Imaging Probe [<Superscript>18</Superscript>F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers

Purpose

[¹⁸F]fluorodeoxysorbitol ([¹⁸F]FDS) is the first radiopharmaceutical specific for a category of bacteria and has the potential to specifically detect Enterobacteriaceae infections. The purpose of this study was to testify the safety and investigate the biodistribution and radiation dosimetry of [¹⁸F]FDS in healthy human bodies.

Procedures

Six healthy subjects were intravenously injected with 320–520 MBq [¹⁸F]FDS. On each subject, 21 whole-body emission scans and a brain scan were conducted at settled time points within the next 4 h. Residence time for each source organ was determined by multi-exponential regression. Absorbed doses for target organs and effective dose were calculated via OLINDA/EXM.

Results

No adverse events due to [¹⁸F]FDS injection were observed in the study. The tracer was cleared rapidly from the blood pool through the urinary system. A small portion was cleared into the gut through the hepatobiliary system. The effective dose (ED) was estimated to be 0.021?±?0.001 mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder wall (0.25?±?0.03 mSv/MBq).

Conclusions

[¹⁸F]FDS is safe and well tolerated. The effective dose was comparable to that of other F-18 labeled radiotracers. [¹⁸F]FDS is suitable for human use from a radiation dosimetry perspective.

     

Optimization of a Labeling and Kit Preparation Method for Ga-68 Labeled DOTATATE,Using Cation Exchange Resin Purified Ga-68 Eluates Obtained from a Tin Dioxide <Superscript>68</Superscript>Ge/<Superscript>68</Superscript>Ga Generator

Purpose

The aim of this study was to optimize a radiolabeling method using cationic processed Ga-68 eluates from a SnO₂-based ⁶⁸Ge/⁶⁸Ga generator, followed by the development of DOTA-Tyr³-Thre⁸-octreotide (DOTATATE) kits.

Procedures

Diluted generator eluates were adsorbed on a SCX resin and desorbed with acidified 5 M NaCl solution. Optimized labeling conditions were determined by variation of pH, using 35 μg DOTATATE and sodium acetate buffer. DOTATATE kits were developed based on optimized radiolabeling conditions, were labeled, and evaluated.

Results

Optimized labeling conditions resulted in a radiolabeling efficiency of around 99 % and radiochemical yield of almost 85 %. Different kit preparation methods did not significantly influence the radiolabeling results. Kits were found to be stable over 3 months.

Conclusion

A labeling method using SCX-processed Ga-68 eluates was optimized. DOTATATE kits specifically for these SCX-processed Ga-68 eluates were successfully formulated. A post-labeling Sep-Pak C18 purification should be optional.

     

Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis

Objective

To determine the efficacy of nasal continuous positive airway pressure (nCPAP) on respiratory distress symptoms and respiratory effort in young infants with acute respiratory syncytial virus bronchiolitis.

Design

Prospective study.

Setting

The paediatric intensive care unit of a university hospital.

Patients

Twelve infants less than 3 months of age, with severe respiratory distress.

Interventions

Respiratory distress was quantified with a specific scoring system. Oesophageal pressure (Pes) was measured during spontaneous ventilation before and after nCPAP, delivered through an infant-adapted ventilator. Simultaneous recording of gastric pressure (Pgas) was performed in the five oldest patients.

Measurements and results

The respiratory distress score decreased after nCPAP, particularly accessory muscles’ use and expiratory wheezing. The breathing pattern was modified, with shorter inspiratory and longer expiratory time. Pes swings and PTPes_insp, two indices of inspiratory effort, were reduced by 54 (±4)% and 59 (±5)%. PTPgas_exp, an indicator of expiratory muscles activity, was completely abolished. A significant correlation was observed between the respiratory distress score and Pes swings at baseline and after nCPAP.

Conclusions

In young infants with severe acute respiratory syncytial virus bronchiolitis, nCPAP rapidly unloads respiratory muscles and improves respiratory distress symptoms.

     

Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

Purpose

In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.

Procedures

Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense? 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.

Results

There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.

Conclusion

MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.

     

pH-Sensitive,Long-Circulating Liposomes as an Alternative Tool to Deliver Doxorubicin into Tumors: a Feasibility Animal Study

Purpose

Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile evaluation of pH-sensitive long-circulating liposomes (SpHL) containing [^99mTc]DOX in 4T1 tumor-bearing BALB/c mice is described.

Procedures

[^99mTc]DOX was radiolabeled by direct method. Liposomes were prepared and characterized. [^99mTc]DOX was encapsulated into liposomes by freezing and thawing. Circulation time for SpHL-[^99mTc]DOX was determined by measuring the blood activity from healthy animals. Biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 24 h after injection.

Results

Blood levels of the SpHL-[^99mTc]DOX declined in a biphasic manner, with an α half-life of 14.1 min and β half-life of 129.0 min. High uptake was achieved in the liver and spleen, due to the macrophages captured. Moreover, tumor uptake was higher than control tissue, resulting in high tumor-to-muscle ratios, indicating higher specificity for the tumor area.

Conclusion

[^99mTc]DOX was successfully encapsulated in liposomes. Biodistribution indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. In summary, these results showed the higher accumulation of SpHL-[^99mTc]DOX in the tumor area, suggesting selective delivery of doxorubicin into tumor.