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.

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.

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.

[99mTc]-Bis-Methionine-DTPA Single-Photon Emission Computed Tomography Impacting Glioma Management: A Sensitive Indicator for Postsurgical/Chemoradiotherapy Response Assessment.

Background: The present study evaluated the prognostic value of [99mTc]MDM (bis-methionine-DTPA) follow-up single-photon emission computed tomography (SPECT) imaging for response assessment to chemoradiotherapy in glioma postoperatively. Materials and Methods: One hundred fourteen glioma patients (80 M:34 F) were followed postoperatively by sequential [99mTc]MDM SPECT, dynamic susceptibility contrast-enhanced (DSCE)-MRI, and magnetic resonance spectroscopy (MRS) at baseline, 6, 12, and 22.5 months postchemoradiotherapy. The quantitative imaging results and the clinical outcome were used for response assessment and for the final diagnosis. The quantitative parameter of [99mTc]MDM SPECT were also used for survival analysis. Results: A significantly (p = 0.001) lower target to nontarget (T/NT) ratio was observed in responders than in nonresponders. The sensitivity and specificity of [99mTc]MDM-SPECT for identifying tumor recurrence from radiation necrosis at a cutoff ratio of 1.90 were estimated at 97.9% and 92%. Whereas, the sensitivity and specificity of DSCE-MRI with the normalized cerebral blood volume (nCBV) cutoff of 3.32 for this differentiation was found to be 84.6% and 93.0%. MRS intensity ratios of Cho/NAA and Cho/Cr provided comparatively lower sensitivity of 81.0% and 85.3% and specificity of 73.0% and 73.7%. T/NT ratios correlated with nCBV (r = 0.775, p < 0.001) and to a moderate extent with Cho/NAA ratios (r = 0.467, p = 0.001). [99mTc]MDM SPECT and DSCE-MRI provided comparable results for predicting response assessment to chemoradiotherapy. There was a final diagnosis in 72 patients, of which 47 cases were tumor recurrence and 25 were radiation necrosis. The Kaplan-Meier analysis indicated that patients with T/NT ratio <1.9 showed prolonged survival (53.8 months) as compared (37.2 months) with those who demonstrated T/NT ratio >1.9 (p = 0.0001). Conclusion: Thus, this low-cost SPECT technique in combination with DSCE-MRI can be used accurately for mapping the disease activity, response assessment, and survival in glioma. [99mTc]MDM SPECT and DSCE-MRI had the same diagnostic efficacy to detect recurrent/residual tumor and radiation necrosis while MRS was inferior to both the techniques.