68 Ga-Pentixafor PET/CT for In Vivo Imaging of CXCR4 Receptors in Glioma Demonstrating a Potential for Response Assessment to Radiochemotherapy: Preliminary Results.

PURPOSE: The aim of this study was to evaluate the diagnostic potential of 68 Ga-pentixafor PET/CT for in vivo CXCR4 receptors imaging in glioma and its possible role in response assessment to radiochemotherapy (R-CT). METHODS: Nineteen (12 men, 7 women) patients with glioblastoma multiforme (GBM) underwent 68 Ga-pentixafor PET/CT, contrast-enhanced MR, and MR spectroscopy. Patients were divided in to 2 groups, that is, group I was the presurgical (n = 9) group in which the scanning was done before surgery, and PET findings were correlated with CXCR4 receptors' density. The group II was the postsurgical (n = 10) group in which the scanning was done before and after R-CT and used for treatment response evaluation. The quantitative analysis of 68 Ga-pentixafor PET/CT evaluated the mean SUV max , SUV mean , SUV peak , and T/B values. MR spectroscopy data evaluated the ratios of tumor metabolites (choline, NAA, creatine). RESULTS: 68 Ga-Pentixafor uptake was noted in all (n = 19) the patients. In the group I, the mean SUV max , SUV mean , SUV peak , and T/B values were found to be 4.5 ± 1.6, 0.60 ± 0.26, 1.95 ± 0.8, and 6.9 ± 4.6, respectively. A significant correlation ( P < 0.005) was found between SUV mean and choline/NAA ratio. Immunohistochemistry performed in 7/9 showed CXCR4 receptors' positivity (intensity 3 + ; stained cells >50.0%). In the group II, the mean SUV max at baseline was 4.6 ± 2.1 and did not differ (4.4 ± 1.6) significantly from the value noted at post-R-CT follow-up PET/CT imaging. At 6 months' clinical follow-up, 4 patients showed stable disease. SUV max and T/B ratios at follow-up imaging were lower (3.70 ± 0.90, 2.64 ± 1.35) than the corresponding values (4.40 ± 2.8; 2.91 ± 0.93) noted at baseline. Six (6/10) patients showed disease progression, and the mean SUV max , and T/B ratio in these patients were significantly ( P < 0.05) higher than the corresponding values at baseline and also higher than that noted in the stable patients. CONCLUSIONS: 68 Ga-Pentixafor PET/CT can be used for in vivo mapping of CXCR4 receptors in GBM. The technique after validation in a large cohort of patients may have added diagnostic value for the early detection of GBM recurrence and for treatment response evaluation.

68 Ga-Pentixafor PET/CT for in-vivo mapping of CXCR4 receptors as potential radiotheranostic targets in soft tissue and bone sarcoma: preliminary results.

OBJECTIVE: To evaluate the diagnostic utility of 68 Ga-Pentixafor PET/CT for in vivo imaging of CXCR4 receptors in soft tissue/bone sarcoma. METHODS: Ten (7M: 3F; mean age = 24.7 ± 14.2 years) consecutive patients with clinical and radiological evidence of bone/soft tissue sarcoma were recruited prospectively whole body 68 Ga-Pentixafor PET/CT imaging was performed at 60-min after tracer administration. After performing standard CT, PET acquisition from head to toe was done (3 min/bed position) in a caudocranial direction. PET/CT data was reconstructed and SUV max , SUV mean values, target-to-background ratio (TBR) and active tumor volume (cc) were computed for the tracer avid lesions. Histopathological and IHC analysis was performed on the surgically excised primary tumors. CXCR4 receptors' intensity was evaluated by visual scoring. RESULTS: The mean SUV max and SUV mean values in the primary tumors were 4.80 ±â€…1.0 (3.9-7.7) and 2.40 ±â€…0.60 (0.9-4.0). The mean TBR and tumor volume (cc) were 1.84 ±â€…1.3 and 312.2 ±â€…285. Diagnosis of osteosarcoma in 7, chondrosarcoma, leiomyosarcoma and synovial sarcoma in 1 patient each was confirmed on HP analysis. Distant metastatic lesions were seen in 3/10 patients. Nuclear CXCR4 receptors' positivity was seen in 5, cytoplasmic in 4 and both pattern seen in 1 patient. The mean CXCR4 receptors' intensity was found to be 7.6 ±â€…2. The highest SUV max value of 7.7 was observed in the patient having both cytoplasmic and nuclear CXCR4 expression. SUV max was found to be poorly correlated ( r  = 0.441) with CXCR4 expression. CONCLUSION: 68 Ga-Pentixafor PET/CT detects CXCR4 receptors over-expressed in sarcoma, its radio-theranostics potential needs detailed evaluation.

[68Ga]Ga-Pentixafor PET/CT imaging for in vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: correlation with quantitative receptors' density by immunochemistry techniques.

PURPOSE: In vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using [68Ga]Ga-Pentixafor PET/CT and to study correlation with quantitative CXCR4 receptors' tissue density by immunochemistry analyses. METHODS: [68Ga]Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77 M: 17F, mean age 60.1 ± 10.1 years) LC patients. CXCR4 receptors' expression on lung mass in all the patients was estimated by immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS) analyses. SUVmax on PET, intensity score on IHC, and mean fluorescence index (MFI) on FACS analyses were measured. RESULTS: A total of 75/94 (79.8%) cases had non-small cell lung cancer (NSCLC), 14 (14.9%) had small cell lung cancer (SCLC), and 5 (5.3%) had lung neuroendocrine neoplasm (NEN). All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.3 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to those in NSCLC and lung NEN. The mean SUVmax in adenocarcinoma (n = 16) was 8.0 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.1) and in not-otherwise specified (NOS) sub-types (n = 5; 5.8 ± 1.5) of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC adenocarcinoma (r = 0.538, p = 0.031) which supports the specific in vivo uptake of [68Ga]Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NEN (r = 0.747, p = 0.147) which may be due to the small sample size. [68Ga]Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cutoff SUVmax = 7.2). This technique presented similar sensitivity (87.5%) and specificity (71.4%) (ROC cutoff SUVmax = 6.7) for differentiating adenocarcinoma and squamous cell variants of NSCLC. CONCLUSION: The high sensitivity and specificity of [68Ga]Ga-Pentixafor PET/CT for in vivo targeting of CXCR4 receptors in lung cancer can thus be used effectively for the response assessment and development of CXCR4-based radioligand therapies in LC.

Evaluation of Reconstruction Algorithms to Validate the NEMA Phantom Results in Clinical Scenario - A Comparative Study Using Time-of-Flight versus Non-Time-of-Flight Positron Emission Tomography Imaging.

Objectives: The objective is to standardize the reconstruction parameters for the time-of-flight (TOF) versus non-TOF positron-emission tomography/computed tomography (PET/CT) imaging data and validation of the same in a clinical setting. Methods: The four spheres (10.0/13.0/17.0/22.0 mm) of the PET phantom (NEMA IQ Nu 2-2001) were filled with four times higher activity of [18F]-NaF than the background (5.3kBq/mL). Imaging (image matrix - 128 × 128 × 47, 2 min, 3D model) was done using two different (TOF/non-TOF) PET scanners. Phantom data were reconstructed in TOF and non-TOF modes for lutetium-yttrium oxyorthosilicate and non-TOF mode for bismuth germanate-based PET scanners. The reconstructed data (by varying iteration and subsets) that provided the best image contrast and signal-to-noise ratio (SNR) were evaluated. The whole-body [18F]-fludeoxyglucose (FDG) PET/CT scans (7-8 frames; 2.0 min/frame) in 16 lymphoma patients were acquired at 60 min after injecting the radioactivity (370.0-444.0 MBq of [18F]-FDG. The clinical PET/CT data were reconstructed using phantom-derived reconstruction parameters and evaluated for image contrast and SNR of the detected lesions. Results: TOF reconstruction at second iteration provided significantly (P ≤ 0.02) higher SNR (20.7) and contrast (contrast recovery coefficient/background variability = 3.21) for the smallest hot lesions (10.0 mm) in the phantom than the non-TOF system. Similarly, in patient data analysis for the selected FDG avid lesions, the SNR values were significantly (P = 0.02) higher (13.3 ± 6.49) in TOF than (11 ± 6.48) in non-TOF system. Further, the small (≤10.0 mm) lesions were seen more distinctly in TOF system. Conclusion: It is thus observed that TOF reconstruction converged faster than the non-TOF, and the applicability of the same may impact the image quality and interpretation in the clinical PET data. The validation of the phantom-based experimental reconstruction parameters to clinical PET imaging data is highly warranted.

Comparison of Internal Dosimetry of 18 F-PSMA-1007 and 68 Ga-PSMA-11-HBED-CC.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men worldwide. Targeting prostate-specific membrane antigen (PSMA) using radiopharmaceuticals has shown promising results for PCa imaging as well as theranostics. 68 Ga-based PSMA imaging is limited by production of small quantities by generator, and it has led to quest for cyclotron produced 18 F-based PSMA ligands. In the current study, we evaluated the biodistribution and internal dosimetry of 18 F-PSMA-1007 and compared it with 68 Ga-PSMA-11-HBED-CC. MATERIALS AND METHODS: A total of 8 patients with histopathologically proven PCa were included in the study, of whom 4 patients underwent 18 F-PSMA-1007, and the other 4 patients underwent 68 Ga-PSMA-11-HBED-CC PET/CT. The biodistribution of both tracers was quantified for different organs by computing SUVs. All the patients underwent 5-point serial imaging to compute equivalent dose to essential organs and whole-body effective dose using OLINDA-based dosimetry. RESULTS: The radiotracer uptake in brain, lacrimal gland, salivary gland, heart, lung, liver, gallbladder, spleen, pancreas, intestine, gluteal muscle, and bone marrow were found to be higher in 18 F-PSMA-1007 PET as compared with 68 Ga PSMA-11 PET. Kidney and urinary bladder showed higher SUV value on 68 Ga-PSMA-11-HBED-CC as compared with 18 F-PSMA-1007.The whole-body effective dose from 18 F-PSMA-1007 (1.46E-02 mSv/MBq) was higher than 68 Ga-PSMA-11-HBED-CC (1.03E-02 mSv/MBq). The highest mean equivalent dose from 18 F-PSMA-1007 was observed in the kidneys (1.48E-01 mGy/MBq), followed by spleen (mean, 1.06E-01 mGy/MBq) and liver (6.80E-02 mGy/MBq), whereas 68 Ga-PSMA-11-HBED-CC equivalent dose was maximum in the kidneys (2.13E-01 mGy/MBq), followed by liver (3.03E-02 mGy/MBq), spleen (2.90E-02 mGy/MBq), adrenals (2.67E-02 mGy/MBq), and urinary bladder (1.89E-02 mGy/MBq). CONCLUSION: Whole-body effective dose from 18 F-PSMA-1007 is higher compared with 68 Ga-PSMA-11-HBED-CC. 18 F-PSMA-1007 shows lesser urinary bladder clearance compared with 68 Ga-PSMA-11-HBED-CC, which can allow better interpretation of prostatic bed without significant radioactive urine interference. 18 F-PSMA-1007 is a cyclotron-produced alternative to generator-produced 68 Ga-PSMA-11-HBED-CC and can emerge as a good diagnostic surrogate for patients planned for 177 Lu-PSMA-617 therapy.

Imaging CXCR4 receptors expression for staging multiple myeloma by using 68Ga-Pentixafor PET/CT: comparison with 18F-FDG PET/CT.

OBJECTIVES: 68Ga-Pentixafor positron emission tomography (PET) imaging targets CXCR4 expression which is overexpressed in multiple myeloma (MM). In this study, we evaluated the diagnostic utility of 68Ga-Pentixafor PET/CT for imaging CXCR4 expression in MM and compared results with 18F-fluorodeoxyglucose (18F-FDG) PET/CT. METHODS: 34 (21M; 13F; median age = 57.5 years) treatment naive multiple myeloma patients were recruited. All the patients underwent 18F-FDG PET/CT and 68Ga-Pentixafor PET/CT imaging. Freshly prepared 68Ga-Pentixafor (148-185 MBq) was injected intravenously and whole-body PET/CT (low-dose CT) was acquired at 1 h post-injection. The pattern of uptake (diffuse, focal or mixed) and the mean SUVmax value of all the lesions (when lesions were ≤5) or of the five most tracer avid lesions (when lesions was >5) were evaluated. Tumor to background ratio (TBRmax) was calculated for both the tracers. Durie Salmon plus staging (DSPS) was used for disease staging on PET and the results were compared with International staging system (ISS). RESULTS: 68Ga-Pentixafor PET/CT showed higher disease extent than seen on 18F-FDG PET/CT in 23/34 patients (68.0%), lesser disease extent in 2/34 (6%) and similar disease extent in 9/34 (26%) patients. Significantly (p < 0.001) higher TBRmax values (5.7; IQR 8.8) were observed on 68Ga-Pentixafor PET/CT as compared to 18F-FDG PET/CT values (2.9; IQR = 4.0). Both the techniques detected extramedullary lesions in six patients. On the other hand, 68Ga-Pentixafor detected medullary lesions in five, whereas, 18F-FDG PET in three patients. Further, only 68Ga-Pentixafor TBRmax correlated significantly (ρ = 0.421; 0.013) with bone marrow plasma cell percentage. 68Ga-Pentixafor PET upstaged more number (9/29) of patients as compared to (4/29) 18F-FDG PET imaging. On the other hand, 18F-FDG PET down-staged 9/29, whereas 68Ga-Pentixafor PET downstaged only 3/29 patients. CONCLUSION: 68Ga-Pentixafor PET/CT evaluated the whole-body disease burden of CXCR4 receptors non-invasively which is not possible by tissue sampling methods. This novel PET tracer has also implication for disease staging. Dual 68Ga-Pentixafor/18F-FDG PET/CT imaging may help in determining the tumor heterogeneity in MM. ADVANCES IN KNOWLEDGE: This CXCR4 targeting PET tracer has a promising role in the development of CXCR4 targeting theranostics and also for response assessment to these therapies including the conventional treatment.

68Ga-Pentixafor PET/CT Demonstrating In Vivo CXCR4 Receptor Overexpression in Rare Lung Malignancies: Correlation with Histologic and Histochemical Findings.

68Ga-pentixafor PET/CT imaging allows noninvasive assessment of C-X-C chemokine receptor type 4 (CXCR4) expression in various malignancies, but its use in rare lung cancer variants has not been reported. Methods: 68Ga-pentixafor PET/CT imaging was performed on 6 patients (3 men, 3 women; mean age, 57.0 ± 16.8 y) with suspected lung masses. Whole-body PET/CT images were acquired 1 h after intravenous injection of 148.0-185.0 MBq of the tracer. PET/CT images were reconstructed and analyzed. The image findings were correlated with histopathologic and quantitative (CXCR4) fluorescence-activated cell sorting analysis. Results: Histopathologic diagnosis of hemangioendothelioma, sarcomatoid carcinoma, and hemangiopericytoma was confirmed in 1 patient each. Lung metastasis was diagnosed in the remaining 3 of 6 patients with primary sarcoma (n = 1), renal cell carcinoma (n = 1), and unknown primary (n = 1). Increased uptake in the primary lung mass, with an SUVmax of 3.0, 6.34, and 13.0, was noted in the hemangiopericytoma, sarcomatoid carcinoma and hemangioendothelioma cases, respectively. The mean SUVmax, mean fluorescence intensity, and percentage of stained cells were highest in hemangioendothelioma. Among 3 patients with lung metastases, the highest SUVmax, 9.5, was in the primary sarcoma patient. Conclusion: 68Ga-pentixafor selectively targets the in vivo whole-body disease burden of CXCR4 receptors. This approach thus holds promise for developing suitable radiotheranostics for lung cancers expressing these targets.

Automated Radiosynthesis, Quality Control, and Biodistribution of Ga-68 Pentixafor: First Indian Experience.

BACKGROUND: Chemokine receptor CXCR4 is overexpressed in more than 27 different human tumors that make it a promising target in oncology. Ga-68 Pentixafor is the most promising positron emission tomography tracer for imaging CXCR4 receptors; hence, the present study was carried out to optimize the radiosynthesis of Ga-68-Pentixafor using fully automated method and the quality control (QC) checks were performed before being used as a clinical product. We also studied the normal biodistribution pattern of Ga-68-pentixafor intended for the use in variety of malignancies. MATERIALS AND METHODS: We optimized the automated radio-synthesis of Ga-68 Pentixafor under good manufacturing practice conditions. A total of 62 productions were carried out in a span of 4 years. Extensive QC tests were performed to check for potency, identity, efficacy, and stability of the tracer. Biodistribution of Ga-68 Pentixafor was investigated in a healthy volunteer to determine normal range of standardized uptake valuemaximum (SUVmax) values in various organs. RESULTS: The radiotracer was prepared successfully in 57/62 productions with radiochemical purity of >99%. Mean radiolabelling efficiency of 73.1% ± 7.7% (n = 57) was obtained with synthesis time approximatively of 34 min. The radiolabeled complex showed no signs of dissociation up to 4 h at the room temperature. Ga-68 Pentixafor upon incubation with human serum was found to be stable at 37°C for 4 h. The highest normal organ uptake was seen in urinary bladder (SUVmean = 146.0), spleen (SUVmean = 6.80) followed by kidneys (SUVmean = 4.99). CONCLUSION: Using the automated radiosynthesis, Ga-68 Pentixafor exhibited good radiolabelling efficiency with excellent in vitro and in vivo stability and favorable biodistribution showing clinical applicability of the tracer.

Humanoid Training Phantom for Positron Emission Tomography-Computed Tomography-Guided Percutaneous Biopsy.

Positron emission tomography-computed tomography (PET-CT)-guided biopsy is being increasing practiced worldwide with indications in sampling of lung, abdominal, bone lesions, and among others. Training for PET-guided Interventions at select centers is carried out under supervision of an expert on real patients, similar to training for interventional radiology procedures. Simulation center training has been shown to be useful in improving efficiency of resident trainees. We report the development of concept, design, and practical application of a simplified humanoid training phantom for PET-guided interventions.

Comparison of the diagnostic utility of 99mTc-PSMA scintigraphy versus 68Ga-PSMA-11 PET/CT in the detection of metastatic prostate cancer and dosimetry analysis: a gamma-camera-based alternate prostate-specific membrane antigen imaging modality.

OBJECTIVE: The present study was performed for head-to-head comparison between 68Ga-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) and 99mTc-PSMA whole-body and regional single-photon emission computed tomography (SPECT)/CT for the detection of prostate cancer metastases. METHODS: Ten patients with metastatic prostate cancer underwent 99mTc-PSMA whole-body scan after intravenous injection of 230-330 MBq 99mTc-PSMA. Anterior and posterior whole-body images were acquired at 10 min, 2, 4 and/or 5/6 h post-injection. Additional SPECT/CT images were acquired for the involved sites, where planar images did not clearly identify the metastatic sites. All patients also underwent whole-body 68Ga-PSMA PET/CT and the results between the two techniques were compared for the detection of the metastatic lesions. Dosimetry analysis of the 99mTc-PSMA studies was performed using the MIRD-OLINDA approach. RESULTS: 68Ga-PSMA PET/CT detected lesions in all 10 patients, whereas 99mTc-PSMA imaging detected lesions in 9/10 patients. 68Ga-PSMA PET/CT imaging identified a total of 112 PSMA avid metastatic lesions compared to 57 (51%) lesions on 99mTc-PSMA imaging. Eighteen out of 57 lesions were detected only on delayed 99mTc-PSMA imaging at 4 h and/or 6 h. The regional 99mTc-PSMA SPECT detected 51/83 (61.0%) lesions seen on 68Ga-PSMA PET/CT. The dosimetry results demonstrated that 99mTc-PSMA provided organs' radiation absorbed/effective doses comparable with 99mTc-PSMA imaging. CONCLUSION: Whole-body 99mTc-PSMA combined with regional SPECT/CT could be a potential alternative to 68Ga-PSMA PET for the detection of the advanced stage metastatic prostate cancer and for response evaluation to PSMA-based targeted therapies.

Correction of Positron Emission Tomography Maximum Intensity Projection Image Artifact Using Retro Reconstruction Method.

Artifacts in positron emission tomography (PET)/computed tomography imaging can result from a number of factors. Presence of imaging artifacts affects interpretation and can sometimes render the image uninterpretable. Correction of artifacts can be attempted by reprocessing of data. In the present study, one PET maximum intensity projection image artifact was corrected by employing the method of retro-reconstruction.

Radiation Exposure to the Personnel Performing Robotic Arm-Assisted Positron Emission Tomography/Computed Tomography-Guided Biopsies.

PURPOSE: The aim of the study was to estimate the radiation burden to personnel performing robotic arm-assisted positron emission tomography/computed tomography (PET/CT)-guided metabolic biopsies and to staff assisting the procedure in a PET/CT facility. MATERIALS AND METHODS: We estimated the whole-body exposures to physicians and staff based on the dose rate measurement with an ionization chamber-based calibrated survey monitor and pocket dosimeters during the robotic arm-assisted 2-[F-18]-fluoro-2-deoxy-D-glucose PET/CT-guided biopsies from September 2016 to February 2017. In addition, we also noted the time to biopsy after injection and total biopsy time during which the staff was exposed to the radiation. RESULTS: In this prospective study, PET/CT-guided biopsy was performed in 50 patients (males - 36, females - 14) with a mean age of 54 ± 15 years (range17-78 years). Of the 50 biopsy procedures, 18 were lung biopsies, 10 were bone biopsies, and 22 biopsies were from abdomen/pelvic lesions. The mean time taken for the procedure was 26 ± 11 min. The mean time elapsed between injection and procedure was 182 ± 85 min and mean injected activity of 138.38 ± 74 MBq. The mean whole-body exposure per procedure to an interventionist and an assistant was 1.88 ± 0.82 µSv and 1.04 ± 0.75 µSv, respectively. The mean exposure rates at 0-m and 1-m distance from the patient were 30.77 ± 14.61 µSv/h and 2.59 ± 1.49 µSv/h, respectively. CONCLUSION: We conclude that the interventionist received the highest mean effective dose as compared to the helping staffs. The occupational radiation exposure was found to be within the limits as specified by the regulatory authorities (International Commission on Radiological Protection-103), and PET/CT-guided biopsies were safe from radiation protection point of view.

18F-Fluorocholine PET/CT Complementing the Role of Dynamic Contrast-Enhanced MRI for Providing Comprehensive Diagnostic Workup in Prostate Cancer Patients With Suspected Relapse Following Radical Prostatectomy.

PURPOSE: The aim of this study was to compare the diagnostic performance of F-fluorocholine (FCH) PET/CT and dynamic contrast-enhanced MRI (DCE-MRI) of pelvis in restaging prostate cancer (PC) patients with biochemical recurrence (BCR) following radical prostatectomy (RP). METHODS: Twenty PC patients who had undergone RP and had BCR were recruited in this study. All the patients underwent whole-body FCH PET/CT and DCE-MRI of the pelvis. An overall pattern of recurrent disease was analyzed, and diagnostic accuracy for the detection of pelvic disease recurrence by the 2 modalities was evaluated by taking histopathologic analysis as the criterion standard. The whole-body FCH PET/CT images were also analyzed separately for the presence of any extra lesion(s). RESULTS: The initial mean Gleason score was 6.3 ± 1.53 (range, 4-9). The mean prostate-specific antigen levels at the time of relapse were 1.9 ± 2.87 ng/mL (range, 0.24-13.2 ng/mL). MRI findings were positive for primary tumor recurrence in the prostate bed in 6 patients (6/20 [30.0%]), pelvic lymph node metastases in 4 patients (4/20 [20.0%]), and for pelvic skeletal metastases in 2 patients (2/20 [10.0%]), respectively. On the other hand, FCH PET/CT results were positive in the corresponding sites in 7 (7/20 [35.0%]), 9 (9/20 [45.0%]), and 2 patients (2/20 [10.0%]), respectively. F-fluorocholine PET/CT and MRI showed comparable results in terms of sensitivity, specificity, and positive and negative predictive values for PC characterization. The whole-body FCH PET/CT was found to be useful in identifying unknown distant metastases in a significant proportion of patients. CONCLUSIONS: The correlative whole-body FCH PET/CT and pelvic DCE-MRI offer a complementary and comprehensive diagnostic workup for better management of PC patients with BCR following RP.

Incremental Value of Cocktail 18F-FDG and 18F-NaF PET/CT Over 18F-FDG PET/CT Alone for Characterization of Skeletal Metastases in Breast Cancer.

PURPOSE: The aim of this study was to evaluate the incremental value of cocktail F-FDG/F-NaF PET/CT over F-FDG PET/CT alone for detection of skeletal metastases in breast cancer patients. METHODS: Seventy patients with locally advanced/recurrent breast cancer were prospectively included. All patients underwent whole-body F-FDG PET/CT and cocktail F-FDG/F-NaF PET/CT within a span of 1 week. Both studies were evaluated to detect presence of skeletal/marrow metastases on PET/CT images by 2 nuclear medicine physicians. Clinical and radiological correlation/follow-up was used as criterion standard. RESULTS: Of 70 patients, 50 (71.0%) had locally advanced breast cancer, and 20 had recurrent breast cancer. On patient-wise analysis, both cocktail PET/CT and F-FDG PET/CT identified skeletal/marrow lesions in 23 (32.8%) of 70 patients. In 8 patients (11.4%), only cocktail PET/CT identified skeletal/marrow lesions, whereas F-FDG PET/CT was negative. In the rest of the 39 patients (55.8%), no skeletal/marrow lesion was identified on both scans. Good correlation was noted between cocktail PET/CT and F-FDG PET/CT results (r = 0.785, P < 0.0001). Cocktail PET/CT detected lesions in significantly more number of patients than F-FDG PET/CT alone (P = 0.007). On lesion-wise analysis, cocktail PET/CT detected more number of lesions in 20 patients as compared with F-FDG-PET/CT alone. Both scans detected same number of lesions in the rest of 11 patients with positive findings. A total of 32 additional lesions were identified on cocktail PET/CT imaging as compared with F PET/CT alone (P < 0.0001). CONCLUSIONS: Cocktail F-FDG and F-NaF PET/CT is superior to F-FDG PET/CT alone for the detection of skeletal/marrow metastases in breast cancer. It can be a better alternative to F-FDG PET/CT alone in facilities where both tracers are available.

Radiosynthesis of [18F]-fluorobenzoate-doxorubicin Using Acylation Approach.

BACKGROUND: Previously, we have labeled doxorubicin with [99Tc] and evaluated its potential as a SPECT agent to detect cancer in tumor bearing mice. In this study, we sought to radiolabel doxorubicin with [18F] using acylation method. METHODS: A quaternary salt of the precursor pentamethylbenzyl-4-(trimethylammonium trifluoromethanesulfonate) benzoate was synthesized and characterized by 1H-NMR. As a first step, 4-[18F]- fluorobenzoic acid (FBA) was synthesized from precursor. In second step, [18F]-FBA was further converted to its corresponding acyl form to radiolabel doxorubicin via acylation reaction. RESULTS: The total reaction time for the synthesis of [18F]-fluorobenzoate-doxorubicin was about 60 minutes. The radiolabeling efficiency of the final product was estimated to be about 59.0% The radiochemical yield for the synthesis of [18F]-FBA and [18F]-fluorobenzoate-doxorubicin were 19.0- 29.0% and 12.0-14.0% respectively. CONCLUSION: Radio synthesis of [18F]-fluorobenzoate-doxorubicin by acylation is a convenient method. However, further improvement in the labeling strategy is required to increase the radiolabeling efficiency and radio synthesis yield. Also, the radiolabeled product needs a detailed pre-clinical evaluation.

99mTc-MDM Brain SPECT for the Detection of Recurrent/Remnant Glioma-Comparison With ceMRI and 18F-FLT PET Imaging: Initial Results.

PURPOSE: To evaluate the diagnostic use of an indigenously developed single vial ready to label (with Tc) kit preparation of bis-methionine-DTPA (Tc-MDM) for the detection of recurrent/residual glioma. MATERIALS AND METHODS: We prospectively studied 32 patients (21 male and 11 female subjects aged 43.0±16.0 years) with clinical suspicion of postoperative recurrent/residual glioma. After radical radiotherapy (54.0-60.0 Gy) with or without concurrent temozolomide as indicated, Tc-MDM SPECT and ceMRI of the brain was performed in all the patients and F-FLT-PET imaging in 16 of 32 patients. RESULTS: MDM SPECT and ceMRI findings were concordant in 28 patients (15 positive and 13 negative). The findings were discordant in the remaining 5 patients, with positive ceMRI and negative MDM-SPECT in 2 patients and negative ceMRI and positive MDM-SPECT in 3 patients. Tc-MDM-SPECT, F-FLT PET, and ceMRI scan findings were positive in 9 of 16 and negative in 5 of 16 patients. In the remaining 2 of 16 patients, both F-FLT-PET and Tc-MDM-SPECT were positive, but ceMRI was negative. Sensitivity, specificity, PPV, NPV, and DA of Tc-MDM-SPECT for diagnosing recurrent/residual glioma were 88.24%, 81.25%, 83.3%, 86.7%, and 84.8%, respectively. CONCLUSIONS: The diagnostic accuracy of Tc-bis-methionine (MDM)-SPECT imaging was comparable with that of ceMRI and F-FLT-PET and may be useful in the management of glioma patients in the postsurgical follow-up period. This imaging technique may be of special interest in peripheral hospitals/developing countries lacking access to expensive PET/cyclotron technology. However, comparison with the existing "gold standard" PET tracers, especially with C-11-methionine-PET imaging and histopathological correlation, is warranted in a large cohort of glioma patients through multicentric studies.

Can 3'-deoxy-3'-(18)F-fluorothymidine or 2'-deoxy-2'-(18)F-fluoro-d-glucose PET/CT better assess response after 3-weeks treatment by epidermal growth factor receptor kinase inhibitor, in non-small lung cancer patients? Preliminary results.

The objectives of this study was to study the diagnostic efficacy of 3'-deoxy-3'-fluorine-18-fluorothymidine ((18)F-FLT) and of 2'-deoxy-2'-(18)F-fluoro-d-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for response evaluation following three weeks treatment by epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in non small cell lung cancer (NSCLC) patients. Fifteen patients of advanced stage (IIIB-IV) NSCLC planned for oral 1st or 2nd/3rd line EGFR-TKI treatment were enrolled in the study. Baseline, prior to treatment, and follow-up after three weeks, (18)F-FLT and (18)F-FDG PET/CT imaging was performed in all patients. The standard uptake lean body mass (SULpeak) and total lesion glycolysis (TLG) values of the hottest lesions were calculated in all patients using semi-quantitative analysis. Statistical analysis on PET semi-quantitative data was used to evaluate the overall survival (OS) and progression free survival (PFS). The patients were either classified as responders or non-responders or at a steady state according to the PET response criteria in solid tumors (PERCIST). The receiver operating characteristic curve (ROC) analysis was done on the (18)F-FDG PET/CT clinical responders, to derive the cut-off values on the corresponding data sets between responders and non responders. Results showed that in responders (18)F-FDG SULpeak values better predicted OS and PFS values when compared to (18)F-FLT SULpeak values and also were a better predictor of OS as compared to the TLG values. In responders, the ROC analysis carried out on (18)F-FLT PET/CT imaging data in responders indicated a decrease of ≥22% in SULpeak and a decrease of ≥0.7 in absolute values. Three (3/15) patients developed resistance to EGFR-TKI treatment at 3 months of follow-up. In conclusion, in both responders and in non responders, patients with NSCLC treated for 3 weeks by EGFR-TKI, both OS and PFS were better predicted by (18)F -FDG SULpeak than by (18)F -FLT SULpeak. Although, the difference was only borderline, yet, (18)F -FDG SULpeak was a better predictor of OS compared to TLG values. However, to validate these findings, studies need to be carried in a larger number of patients.