Does Measurement of First-Order and Heterogeneity Parameters Improve Response Assessment of Bone Metastases in Breast Cancer Compared to SUVmax in [18F]fluoride and [18F]FDG PET?

Molecular Imaging and Biology - To establish whether first-order statistical features from [18F]fluoride and 2-deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron emission tomography/x-ray computed...     

Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer

Purpose

Positron emission tomography using 3??-deoxy-3??-[¹⁸F]fluorothymidine ([¹⁸F]FLT) has been suggested as a means for monitoring response to chemotherapy. The aim of this study was to evaluate the validity of simplified uptake measures for assessing response to chemotherapy using [¹⁸F]FLT in locally advanced breast cancer (LABC).

Procedures

Fifteen LABC patients underwent dynamic [¹⁸F]FLT scans both prior to and after the first cycle of chemotherapy with fluorouracil, epirubicin or doxorubicin, and cyclophosphamide. The net uptake rate constant of [¹⁸F]FLT, K _i , determined by non-linear regression (NLR) of an irreversible two-tissue compartment model was used as the gold standard. In addition to Patlak graphical analysis, standardised uptake values (SUV) and tumour-to-whole blood ratio (TBR) were used for analysing [¹⁸F]FLT data. Correlations and relationships between simplified uptake measures and NLR before and after chemotherapy were assessed using regression analysis.

Results

No significant differences in both pre- and post-chemotherapy relationships between any of the simplified uptake measures and NLR were found. However, changes in SUV between baseline and post-therapy scans showed a significant negative bias and slope less than one, while TBR did not.

Conclusions

In LABC, TBR instead of SUV may be preferred for monitoring response to chemotherapy with [¹⁸F]FLT.     

Visualization of Somatostatin Receptors in Prostate Cancer and its Bone Metastases with Ga-68–DOTATOC PET/CT

Purpose  

To assess DOTATOC-affine somatostatin receptor expression in advanced prostate cancer and its bone metastases with regard to DOTATOC-mediated receptor therapies, using a Ga-68–DOTATOC PET/CT.     

Correction to: Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

Molecular Imaging and Biology -     

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

Molecular Imaging and Biology - Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4...     

PET Imaging of l-Type Amino Acid Transporter (LAT1) and Cystine-Glutamate Antiporter (xc−) with [18F]FDOPA and [18F]FSPG in Breast Cancer Models

Molecular Imaging and Biology - The present study describes the analysis of amino acid transporters ASCT1, ASCT2, LAT1, and xc? in breast cancer under normoxic and hypoxic conditions....     

Biodistribution and Radiation Dosimetry of the Carbonic Anhydrase IX Imaging Agent [18 F]VM4-037 Determined from PET/CT Scans in Healthy Volunteers

Purpose

[¹⁸?F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [¹⁸?F]VM4-037 using whole-body PET/CT scans in healthy human volunteers.

Procedures

Successive whole-body PET/CT scans were performed after intravenous injection of [¹⁸?F]VM4-037 in four healthy humans. The radiotracer uptakes in different organs were determined from the analysis of the PET scans. Human radiation doses were estimated using OLINDA/EXM software.

Results

High uptake of [¹⁸?F]VM4-037 was observed in the liver and kidneys, with little clearance of activity during the study period, with mean standardized uptake values of ~35 in liver and ~22 in kidneys at ~1 h after injection. The estimated effective dose was 28?±?1 μSv/MBq and the absorbed doses for the kidneys and liver were 273?±?31 and 240?±?68 μGy/MBq, respectively, for the adult male phantom. Hence, the effective dose would be 10?±?0.5 mSv for the anticipated injected activity of 370 MBq, and the kidney and liver doses would be 101?±?11 and 89?±?25 mGy, respectively.

Conclusions

[¹⁸?F]VM4-037 displayed very high uptake in the liver and kidneys with little clearance of activity during the study period, resulting in these organs receiving the highest radiation doses among all bodily organs. Though the effective dose and the organ doses are within the limits considered as safe, the enhanced uptake of [¹⁸?F]VM4-037 in the kidneys and liver will make the compound unsuitable for imaging overexpression of CA-IX in those two organs. However, the tracer may be suitable for imaging overexpression of CA-IX in lesions in other regions of the body such as in the lungs or head and neck region.     

Longitudinal PET Imaging of α7 Nicotinic Acetylcholine Receptors with [18F]ASEM in a Rat Model of Parkinson’s Disease

Molecular Imaging and Biology - The nicotinic acetylcholine alpha-7 receptors (α7R) are involved in a number of neuropsychiatric and neurodegenerative brain disorders such as Parkinson’s...     

The Relationship Between Serial [18 F]PBR06 PET Imaging of Microglial Activation and Motor Function Following Stroke in Mice

Purpose

Using [¹⁸?F]PBR06 positron emission tomography (PET) to characterize the time course of stroke-associated neuroinflammation (SAN) in mice, to evaluate whether brain microglia influences motor function after stroke, and to demonstrate the use of [¹⁸?F]PBR06 PET as a therapeutic assessment tool.

Procedures

Stroke was induced by transient middle cerebral artery occlusion (MCAO) in Balb/c mice (control, stroke, and stroke with poststroke minocycline treatment). [18 F]PBR06 PET/CT imaging, rotarod tests, and immunohistochemistry (IHC) were performed 3, 11, and 22 days poststroke induction (PSI).

Results

The stroke group exhibited significantly increased microglial activation, and impaired motor function. Peak microglial activation was 11 days PSI. There was a strong association between microglial activation, motor function, and microglial protein expression on IHC. Minocycline significantly reduced microglial activation and improved motor function by day 22 PSI.

Conclusion

[18 F]PBR06 PET imaging noninvasively characterizes the time course of SAN, and shows increased microglial activation is associated with decreased motor function.     

Assessment of the Novel Estrogen Receptor PET Tracer 4-Fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES) by PET Imaging in a Breast Cancer Murine Model

Purpose

The aim of this study was to compare the in vivo stability, uptake, and positron emission tomography (PET) imaging performance of a novel estrogen receptor PET tracer, 4-fluoro-11β-methoxy-16α-[¹⁸F]fluoroestradiol (4FMFES), with 16α-[¹⁸F]fluoroestradiol (FES).

Procedures

MC7-L1 and MC4-L2 (ER+) cell lines and their ERα-knockdown variants (ERαKD) were implanted subcutaneously in Balb/c mice. After 21 days, mice were imaged using either FES or 4FMFES. One hour post-injection, static images were acquired for 30 min and the tumor %ID/g uptake values were derived. Biodistribution data were also obtained 1 h following the injection of either FES or 4FMFES. Blood samples were taken at different times and analyzed on thin-layer chromatography to quantify the presence of radiometabolites for each radiotracer. To assess specific targeting to the estrogen receptors, mice bearing only ER+ tumors were treated with the competitive ER inhibitor fulvestrant 48 h prior to imaging with 4FMFES.

Results

Metabolic stability was found to be similar for both tracers in mice. Both FES and 4FMFES differentiated ER+ tumors from ERαKD tumors in biodistribution and PET imaging studies. 4FMFES achieved a significantly higher %ID/g uptake in ER+ tumors and MC4-L2 ERαKD tumors than FES in the PET imaging studies. Also, tumor-to-background ratio was higher in ER+ tumors using 4FMFES compared to FES. Dissection data showed a significantly higher %ID/g in all tested cell lines and ER-rich tissues using 4FMFES versus FES. Fulvestrant-treated mice had either low or undetectable tumor uptake.

Conclusion

In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.     

Hybrid MicroPET Imaging for Dosimetric Applications in Mice: Improvement of Activity Quantification in Dynamic MicroPET Imaging for Accelerated Dosimetry Applied to 6-[18 F]Fluoro-l-DOPA and 2-[18 F]Fluoro-l-Tyrosine

Purpose

Dynamic microPET imaging has advantages over traditional organ harvesting, but is prone to quantification errors in small volumes. Hybrid imaging, where microPET activities are cross-calibrated using post scan harvested organs, can improve quantification. Organ harvesting, dynamic imaging and hybrid imaging were applied to determine the human and mouse radiation dosimetry of 6-[18 F]fluoro-l-DOPA and 2-[18 F]fluoro-l-tyrosine and compared.

Procedures

Two-hour dynamic microPET imaging was performed with both tracers in four separate mice for 18 F-FDOPA and three mice for 18 F-FTYR. Organ harvesting was performed at 2, 5, 10, 30, 60 and 120 min post tracer injection with n?=?5 at each time point for 18 F-FDOPA and n?=?3 at each time point for 18 F-FTYR. Human radiation dosimetry projected from animal data was calculated for the three different approaches for each tracer using OLINDA/EXM. S-factors for the MOBY phantom were used to calculate the animal dosimetry.

Results

Correlations between dose estimates based on organ harvesting and imaging was improved from r?=?0.997 to r?=?0.999 for 18 F-FDOPA and from r?=?0.985 to r?=?0.996 (p?<?0.0001 for all) for 18 F-FTYR by using hybrid imaging.

Conclusion

Hybrid imaging yields comparable results to traditional organ harvesting while partially overcoming the limitations of pure imaging. It is an advantageous technique in terms of number of animals needed and labour involved.     

PIK3CA Mutational Status Is Associated with High Glycolytic Activity in ER+/HER2− Early Invasive Breast Cancer: a Molecular Imaging Study Using [18F]FDG PET/CT

Molecular Imaging and Biology - In PIK3CA mutant breast cancer, downstream hyperactivation of the PI3K/AKT/mTOR pathway may be associated with increased glycolysis of cancer cells. The purpose of...     

Letter to the Editor re: “Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake”

Molecular Imaging and Biology -     

PET/CT Imaging of Human TNFα Using [89Zr]Certolizumab Pegol in a Transgenic Preclinical Model of Rheumatoid Arthritis

Molecular Imaging and Biology - Tumor necrosis factor alpha (TNFα) drives inflammation and bone degradation in patients with rheumatoid arthritis (RA). Some RA patients experience a rapid...     

Reply to Letter to Editor RE: “Integration of PET/CT Radiomics and Semantic Features for Differentiation Between Active Pulmonary Tuberculosis and Lung Cancer”

Molecular Imaging and Biology -     

Baseline [<Superscript>18</Superscript>F]FMISO μPET as a Predictive Biomarker for Response to HIF-1α Inhibition Combined with 5-FU Chemotherapy in a Human Colorectal Cancer Xenograft Model

Purpose

The purpose of this study was to characterize imaging biomarkers for the potential benefit of hypoxia-inducible factor-1 (HIF-1)α inhibition (by PX-12) during 5-fluorouracil (5-FU) chemotherapy in the treatment of colorectal cancer (CRC).

Procedures

Therapy response to 5-FU?±?PX-12 was assessed with baseline [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) and longitudinal 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) positron emission computed tomography (μPET/CT) in CRC xenograft model (n?=?36) during breathing of a hypoxic (10 % O₂) or normoxic (21 % O₂) atmosphere. Ex vivo, immunohistochemistry was performed.

Results

Baseline [¹⁸F]FMISO uptake and relative tumor volume (RTV) 2 days after 5-FU or 5-FU?+?PX-12 administration correlated significantly (p?≤?0.01). Under hypoxic breathing conditions, [¹⁸F]FDG uptake (?53.1?±?8.4 %) and Ki67 expression (?16 %) decreased and RTV stagnated in the 5-FU?+?PX-12 treatment group, but not in 5-FU alone-treated tumors. Under normoxic breathing, [¹⁸F]FDG uptake (?23.5?±?15.2 % and ?72.8?±?7.1 %) and Ki67 expression (?5 % and ?19 %) decreased and RTV stagnated in both the 5-FU and the combination treatment group, respectively.

Conclusion

Baseline [¹⁸F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.

     

How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1 h: the Stanford Approach

Purpose

To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h.

Procedures

In this prospective clinical trial, 20 children and young adults (11–30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [¹⁸F]FDG (2–3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher’s exact tests.

Results

Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol “off label” as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [¹⁸F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %).

Conclusion

Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.

     

Letter to the Editor: “Integration of PET/CT Radiomics and Semantic Features for Differentiation Between Active Pulmonary Tuberculosis and Lung Cancer”

Molecular Imaging and Biology -     

Whole Body Biodistribution and Radiation Dosimetry in Humans of a New PET Ligand, [18F]-FEPPA, to Image Translocator Protein (18 kDa)

Purpose

[¹⁸F]-FEPPA is a translocator protein (18 kDa, TSPO) positron emission tomography (PET) radiotracer. Radiation dosimetry was estimated from the whole body biodistribution, taking into consideration TSPO rs6971 (Ala147Thr) polymorphism.

Procedures

[¹⁸F]-FEPPA whole body PET scans were acquired for six healthy subjects. Time–activity curves were generated from regions of interest of nine organs, from which normalized accumulated activities were calculated and thus internal dose, using OLINDA/EXM 1.1. Genotyping of rs6971, associated with high- and low-affinity [¹⁸F]-FEPPA binding (high-affinity binder (HAB) and low-affinity binder (LAB)), was performed.

Results

Five subjects exhibited the C/C (HAB) allele, and the other carried the minor allele T/T (LAB). The LAB whole body biodistribution showed highest radioactivity accumulation in bladder, whereas in HABs, the spleen received the highest dose. The effective dose of the single LAB (16.3 μSv/MBq) was 23 % less than the mean of the HABs (21.0?±?2.9 μSv/MBq). When including all subjects, the effective dose was 20.2?±?3.0 μSv/MBq.

Conclusions

[¹⁸F]-FEPPA radiation dose is consistent with other ¹⁸F-labeled radioligands and the Ala147Thr genotype agreed with [¹⁸F]-FEPPA distribution.     

Cross-sectional and Test-Retest Characterization of PET with [<Superscript>18</Superscript>F]FP-(+)-DTBZ for β Cell Mass Estimates in Diabetes

Purpose

The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of β cell mass (BCM) by positron emission tomography (PET) with [¹⁸F]fluoropropyl-dihydrotetrabenazine ([¹⁸F]FP-(+)-DTBZ).

Procedures

We evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BP_ND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm. Metabolic function was evaluated by stimulated c-peptide measurements.

Results

Pancreatic BP_ND was significantly decreased in patients with type 1 diabetes relative to controls and the test-retest variability was 9.4 %.

Conclusions

Pancreatic VMAT2 content is significantly reduced in long-term diabetes patients relative to controls and repeat scans are sufficiently reproducible to suggest the feasibility clinically VMAT2 measurements in longitudinal studies of new onset diabetes.