High quality imaging and dosimetry for yttrium-90 (90Y) liver radioembolization using a SiPM-based PET/CT scanner.

PURPOSE: Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from 99mTc macroaggregated albumin (MAA) SPECT/CT with post-treatment 90Y PET/CT for absorbed dose values, and to evaluate image quality of 90Y SiPM-based PET/CT. METHODS: Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning 99mTc-MAA SPECT/CT and post-therapy 90Y PET/CT were assessed. 90Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale. RESULTS: The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from 99mTc-MAA SPECT/CT and 90Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (P = 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (P = 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from 99mTc-MAA SPECT/CT and 90Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (P = 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (P = 0.17), respectively for resin microspheres. Image quality of 90Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively. CONCLUSIONS: 99mTc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of 90Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.

Two Patient Studies of a Companion Diagnostic Immuno-Positron Emission Tomography (PET) Tracer for Measuring Human CA6 Expression in Cancer for Antibody Drug Conjugate (ADC) Therapy.

An antigen binding fragment (BFab) derived from a tumor-associated mucin 1-sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [64Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with 18F-2-fluoro-2-deoxyglucose ([18F]FDG: 10 mCi), followed by [64Cu]-DOTA-BFab ([64Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [18F]FDG-PET scan. 4 weeks later the patient received of [64Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [18F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [64Cu]BFab at 1 and 24 hours after tracer administration. The [64Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [64Cu]BFab-PET signals.

Repeatability of hypoxia PET imaging using [¹8F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial.

PURPOSE: Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [(18)F]HX4 in patients with head and neck and lung cancer. METHODS: Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [(18)F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient. RESULTS: All parameters of [(18)F]HX4 uptake were significantly correlated between scans: SUVmax (r = 0.958, p < 0.001), SUVmean (r = 0.946, p < 0.001), TBRmax (r = 0.962, p < 0.001) and HV1.2 (r = 0.995, p < 0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65 ± 0.14. CONCLUSION: Repeated hypoxia PET scans with [(18)F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [(18)F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

Role of positron emission tomography in management of sinonasal neoplasms--a single institution's experience.

OBJECTIVE: The objective of the study is to examine the utility of positron emission tomography (PET) for staging and restaging after treatment of paranasal sinus carcinomas. STUDY DESIGN: Retrospective data review was done. SUBJECTS AND METHODS: Patients selected underwent PET for sinonasal neoplasms from 2003 to 2008 at a tertiary care referral center. RESULTS: Seventy-seven scans were reviewed from 31 patients. The pathologies included olfactory neuroblastoma (n = 9), squamous cell carcinoma (n = 6), sinonasal undifferentiated carcinoma (n = 6), sinonasal melanoma (n = 6), and minor salivary gland carcinomas (n = 4). The positive predictive value of studies performed for restaging at the primary, neck, and distant sites were 56%, 54%, and 63%; negative predictive values were 93%, 100%, and 98%, respectively. During restaging, 32% of patients were accurately upstaged secondary to neck or distant site involvement. CONCLUSION: Positron emission tomography serves as a useful adjunct to conventional imaging in the management of sinonasal malignancies. Negative studies are effective in predicting absence of disease as seen in the consistently high-negative predictive values. Positive studies need to be viewed cautiously given the high rate of false-positive studies. When viewed in conjunction with clinical examination, endoscopic assessment, and focused biopsies, they may effectively result in a more accurate assessment of the extent of disease.

A recovery coefficient method for partial volume correction of PET images.

OBJECTIVES: Correction of the "partial volume effect" has been an area of great interest in the recent times in quantitative PET imaging and has been mainly studied with count recovery models based upon phantoms that incorporate hot spheres in a cold background. The goal of this research study was to establish a similar model that is closer to a biological imaging environment, namely hot spheres/lesions in a warm background and to apply this model in a small cohort of patients. METHODS: A NEMA phantom with six spheres (diameters 1-3.7 cm) was filled with (18)FDG to give sphere:background activity ratios of 8:1, 6:1, and 4:1 for three different acquisitions on a Philips Allegro scanner. The hot sphere SUVmax and the background average SUV were measured for calculation of recovery coefficients (RCs). Using the RCs, the lesion diameters, and the lesion:background ratio, the SUVmax of 64 lesions from 17 patients with biopsy proven lung cancer were corrected. RESULTS: The RCs versus sphere diameters produced characteristic logarithmic curves for each phantom (RCs ranged from 80% to 11%). From a cohort of 17 patients with biopsy proven lung cancer, 64 lesions combined had a mean SUVmax of 7.0 and size of 2.5 cm. After partial volume correction of the SUVmax of each lesion, the average SUVmax increased to 15.5. CONCLUSIONS: Hot spheres in a warm background more closely resemble the actual imaging situation in a living subject when compared to hot spheres in a cold background. This method could facilitate generation of equipment specific recovery coefficients for partial volume correction. The clinical implications for the increased accuracy in SUV determination are certainly of potential value in oncologic imaging.

Comparison of diffuse optical tomography of human breast with whole-body and breast-only positron emission tomography.

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Administered activity and outcomes of glass versus resin (90)Y microsphere radioembolization in patients with colorectal liver metastases.

BACKGROUND: Given the differences in size, specific activity, and dosing methods for glass yttrium-90 microspheres ((90)Y-glass) and resin (90)Y microspheres ((90)Y-resin), these therapies may expose the liver to different amounts of radiation, thereby affecting their efficacy and tolerability. We aimed to compare the prescribed activity of (90)Y-glass and (90)Y-resin for real-world patients undergoing selective internal radiation therapy (SIRT) for liver-dominant metastatic colorectal cancer (mCRC) and to assess efficacy and safety outcomes in these patients. METHODS: We examined the records of 28 consecutive patients with unresectable colorectal liver metastases treated with SIRT between June 2008 and May 2011 at our institution. Using baseline CT and MR images, we calculated a projected activity as if we had used the other product and compared it to the actual prescribed activity of (90)Y-glass and (90)Y-resin for each SIRT treatment per manufacturer guidelines. Progression and adverse events were evaluated at follow up visits. Survival was analyzed by the Kaplan-Meier method. RESULTS: For (90)Y-glass treatments with a mean prescribed (90)Y activity of 1.77 GBq, the mean projected (90)Y-resin activity was 0.84 GBq. For (90)Y-resin treatments with a mean prescribed (90)Y activity of 1.05 GBq, the mean projected (90)Y-glass activity was 2.48 GBq. The median survival was 9.3 months versus 18.2 months for (90)Y-glass and (90)Y-resin, respectively (P=0.292). During the second year after SIRT, the hazard ratio of death for patients treated with (90)Y-glass versus (90)Y-resin was 4.0 (95% CI: 1.3, 12.3; P=0.017). No significant difference in progression, adverse events or liver toxicity was observed. CONCLUSIONS: Using manufacturer recommended guidelines, (90)Y-resin delivers significantly less activity than (90)Y-glass to patients with liver-dominant mCRC undergoing SIRT with no significant difference in adverse events and a trend toward improved survival.

Polarization Effects in Optical Coherence Tomography of Various Biological Tissues.

Polarization sensitive optical coherence tomography (PS-OCT) was used to obtain spatially resolved ex vivo images of polarization changes in skeletal muscle, bone, skin and brain. Through coherent detection of two orthogonal polarization states of the signal formed by interference of light reflected from the biological sample and a mirror in the reference arm of a Michelson interferometer, the depth resolved change in polarization was measured. Inasmuch as any fibrous structure will influence the polarization of light, PS-OCT is a potentially powerful technique investigating tissue structural properties. In addition, the effects of single polarization state detection on OCT image formation is demonstrated.

Determination of burn depth by polarization-sensitive optical coherence tomography.

An assessment of burn depth is a key step in guiding the treatment of patients who have sustained thermal injuries. Polarization-sensitive optical coherence tomography (PS-OCT) might eventually provide the physician with a quantitative estimate of actual burn depth. Burns of various depths were induced by contacting rat skin with a brass rod preheated to 75 degrees C for 5, 15, or 30 s. Thermal injury denatured the collagen in the skin, and PS-OCT imaged the resulting reduction of birefringence through the depth-resolved changes in the polarization state of light propagated and reflected from the sample. Stokes vectors were calculated for each point in the PS-OCT images and the reduction in the rate of phase retardation between two orthogonal polarizations of light (deg/microm) was found to show a consistent trend with burn exposure time. PS-OCT is a noninvasive technique with potential to give the physician the information needed to formulate an optimal treatment plan for burn patients.

Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post-Radioembolization (90)Y PET.

BACKGROUND: Radioembolization with Yttrium-90 ((90) Y) microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC). Using post-treatment (90) Y positron emission tomography/computerized tomography (PET/CT) scans, the distribution of microspheres within the liver can be determined and quantitatively assessed. We studied the radiation dose of (90) Y delivered to liver and treated tumors. METHODS: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres(®)) to the frequency of complications with modified response evaluation criteria in solid tumors (mRECIST). (90) Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL) to an absorbed dose (Gy). RESULTS: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy; range 0-570 Gy). Tumor response by mRECIST criteria was performed for 48 tumors that had follow-up scans. There were 21 responders (mean dose 215 Gy) and 27 non-responders (mean dose 167 Gy). The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p = 0.099). Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy). There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p = 0.036). CONCLUSION: Our cohort of patients showed a possible dose-response trend for the tumors. Collateral dose to normal liver is non-trivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose that the tumor or normal liver received.

A Dedicated Breast Positron Emission Tomography Scanner: Proof of Concept.

PURPOSE: This study developed and tested a novel scanner constructed for dedicated positron emission tomography (PET) of the breast. The breast PET (B-PET) scanner is designed with two opposing detectors using curve plate NaI(Tl) detectors to achieve a combination of high spatial resolution and energy resolution. METHODS: Phantom and clinical studies (n = 20) with 18F-fluorodeoxyglucose were carried out on the whole-body Philips Allegro scanner and the B-PET scanner. Images were subjectively assessed by an expert panel. RESULTS: Phantom studies indicated improved contrast for B-PET over conventional PET. Of the 20 clinical studies with breast cancer demonstrated on whole-body fluorodeoxyglucose PET, 10 B-PET scans showed agreement. Of the remaining 10 studies, three had breasts that were too small to be imaged, four had lesions that were too deep to be captured in the field of view, and three were excluded due to technical errors. CONCLUSIONS: Compared with conventional PET, B-PET images provided greater detail in breast lesions suggesting that the low-cost and relatively simple design of B-PET may potentially be an important adjunct to traditional mammography in helping determine the nature of a lesion.

Use of lymphoscintigraphy in radiation treatment of primary breast cancer in the context of lymphedema risk reduction.

PURPOSE: The goal of this study was to determine the feasibility of SPECT/CT scintigraphic method for mapping lymphatic drainage for radiation therapy of breast cancer. MATERIALS AND METHODS: Thirty-six patients were enrolled in a SPECT/CT lymphoscintigraphy study. (99m)Tc sulfur colloid (1mCi) was injected intradermally in the ipsilateral arm. After 5-8h post-injection, the SPECT/CT scans were taken and analyzed on a GE eNTRGRA system. The SPECT/CT images were co-registered in the treatment planning system (TPS). The original treatment plan was recreated for nodal dosimetry. Intensity modulated radiation therapy (IMRT) planning was performed for reducing lymph node dose for reducing arm lymphedema. RESULTS: The number of lymph nodes varied from 0 to 10 with a mean value of 3.4±5.4 nodes. The location of nodes varied in the axillary, supraclavicular, and breast regions depending upon the surgical procedure and the extent of the disease. The prescribed radiation dose to the breast varied from 45 to 50.4Gy depending on the disease pattern in 32 evaluated patients having CT data. The dose to lymph nodes varied from 0 to 61.8Gy depending upon the location and the radiation technique used. SPECT/CT study in conjunction with IMRT plan showed that it is possible to decrease nodal dose and thereby potentially reduce the risk of developing arm lymphedema. CONCLUSIONS: The SPECT/CT device provides a novel method to map the lymph nodes in the radiation treatment fields that could be used to tailor the radiation dose.

The Role of Functional Imaging in Radiotherapy Planning and Management for Gynecologic Malignancies.

In addition to allowing much greater technical precision, the modern era allows investigation of target physiology and it is the potential incorporation of physiologic information into the treatment-planning rubric that gives modern PET-CT its allure and promise. Although oncologic PET scanning has been clinically available for more than 10 years, it is only recently that sufficient investigative and retrospective data have become available to confidently assert that future radiotherapy treatment planning will include functional imaging as an obligatory dimension of clinical characterization for most gynecologic tumors. This article explores the role of functional imaging in radiotherapy planning and management of gynecologic malignancies.

Maximum standardized uptake value from staging FDG-PET/CT does not predict treatment outcome for early-stage non-small-cell lung cancer treated with stereotactic body radiotherapy.

PURPOSE: To perform a retrospective review to determine whether maximum standardized uptake values (SUV(max)) from staging 2-deoxy-2- [(18)F] fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) studies are associated with outcomes for early-stage non-small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Seventy-two medically inoperable patients were treated between October 17, 2003 and August 17, 2007 with SBRT for T1-2N0M0 NSCLC. SBRT was administered as 60 Gy in 3 fractions, 50 Gy in 5 fractions, or 50 Gy in 10 fractions using abdominal compression and image-guided SBRT. Cox proportional hazards regression was performed to determine whether PET SUV(max) and other variables influenced outcomes: mediastinal failure (MF), distant metastases (DM), and overall survival (OS). RESULTS: Biopsy was feasible in 49 patients (68.1%). Forty-nine patients had T1N0 disease, and 23 had T2N0 disease. Median SUV(max) was 6.55 (range, 1.5-21). Median follow-up was 16.9 months (range, 0.1-37.9 months). There were 3 local failures, 8 MF, 19 DM, and 30 deaths. Two-year local control, MF, DM, and OS rates were 94.0%, 10.4%, 30.1%, and 61.3%, respectively. In univariate analysis, PET/CT SUV(max), defined either as a continuous or dichotomous variable, did not predict for MF, DM, or OS. On multivariable analysis, the only predictors for overall survival were T1 stage (hazard ratio = 0.331 [95% confidence interval, 0.156-0.701], p = 0.0039) and smoking pack-year history (hazard ratio = 1.015 [95% confidence interval, 1.004-1.026], p = 0.0084). CONCLUSIONS: Pretreatment PET SUV(max) did not predict for MF, DM, or OS in patients treated with SBRT for early-stage NSCLC.