Change In SUVmax Research Articles

Lesion Dosimetry for [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm3 The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P = 0.005), 0.74 (P = 0.046) between the baseline PET SUVmax and the lesion ADRPT, and -0.81 (P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was -0.88 (P = 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.

Is Prone Position [18F]FDG PET/CT Useful in Reducing Respiratory Motion Artifacts in Evaluating Hepatic Lesions?

Prone position is useful in reducing respiratory motion artifacts in lung nodules on 2-Deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT). However, whether prone position PET/CT is useful in evaluating hepatic lesions is unknown. Thirty-five hepatic lesions from 20 consecutive patients were evaluated. The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of both standard supine position PET/CT and additional prone position PET/CT were evaluated. No significant difference in SUVmax (4.41 ± 2.0 vs. 4.23 ± 1.83; p = 0.240) and MTV (5.83 ± 6.69 vs. 5.95 ± 6.24; p = 0.672) was observed between supine position PET/CT and prone position PET/CT. However, SUVmax changes in prone position PET/CT varied compared with those in supine position PET/CT (median, -4%; range: -30-71%). Prone position PET/CT was helpful when [18F]FDG uptake of the hepatic lesions was located outside the liver on supine position PET/CT (n = 4, SUVmax change: median 15%; range: 7-71%) and there was more severe blurring on supine position PET/CT (n = 6, SUVmax change: median 11%; range: -3-32%). Unlike in lung nodules, prone position PET/CT is not always useful in evaluating hepatic lesions, but it may be helpful in individual cases such as hepatic dome lesions.

Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n=163) and follow-up FDG-PET/CT at 3 or 6 months (n=71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P=.006), >12.3 for PFS (aHR, 2.80, P=.011), and >12.6 for OS (aHR, 3.00, P=.003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P=.018), and 53% at 6 months (aHR, 0.12, P=.046) were associated with improved local failure-free survival. Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

Utility of 18F-FDG uptake in predicting major pathological response to neoadjuvant immunotherapy in patients with resectable non‑small cell lung cancer

PurposeThe aim of present study was to investigate the efficiency of 18F-FDG uptake in predicting major pathological response (MPR) in resectable non-small cell lung cancer (NSCLC) patients with neoadjuvant immunotherapy. MethodsA total of 104 patients with stage I-IIIB NSCLC were retrospectively derived from National Cancer Center of China, of which 36 cases received immune checkpoint inhibitors (ICIs) monotherapy (I-M) and 68 cases with ICI combination therapy (I-C). 18F-FDG PET-CT scans were performed at baseline and after neoadjuvant therapy (NAT). Receiver‐operating characteristic (ROC) curve analyses were conducted and area under ROC curve (AUC) was calculated for biomarkers including maximum standardized uptake value (SUVmax), inflammatory biomarkers, tumor mutation burden (TMB), PD-L1 tumor proportion score (TPS) and iRECIST. ResultsFifty-four resected NSCLC tumors achieved MPR (51.9%, 54/104). In both neoadjuvant I-M and I-C cohorts, post-NAT SUVmax and the percentage changes of SUVmax (ΔSUVmax%) were significantly lower in the patients with MPR versus non-MPR (p < 0.01), and were also negatively correlated with the degree of pathological regression (p < 0.01). The AUC of ΔSUVmax% for predicting MPR was respectively 1.00 (95% CI: 1.00–1.00) in neoadjuvant I-M cohort and 0.94 (95% CI: 0.86–1.00) in I-C cohort. Baseline SUVmax had a statistical prediction value for MPR only in I-M cohort, with an AUC up to 0.76 at the threshold of 17.0. ΔSUVmax% showed an obvious advantage in MPR prediction over inflammatory biomarkers, TMB, PD-L1 TPS and iRECIST. Conclusion18F-FDG uptake can predict MPR in NSCLC patients with neoadjuvant immunotherapy.

Depth of metabolic response at interim PET and survival outcomes among patients with primary refractory and early relapsing diffuse large B-cell lymphoma (DLBCL).

7543 Background: Total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) may improve upon standard 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)-based assessment of advanced DLBCL during treatment. We report the association of TMTV and SUVmax changes at interim PET-CT (PET2) on survival outcomes in patients with primary refractory DLBCL (prDLBCL) and early relapsing DLBCL (erDLBCL). Methods: Adult patients with prDLBCL (less than a complete response (CR) or progression by the end of treatment (EOT)) or erDLBCL (CR at EOT with relapse within 12 months) between 2005 and 2019 at Mayo Clinic Rochester were included. The % change (Δ) from baseline to PET2 (after 2 cycles of 1L therapy) of TMTV and SUVmax were measured. A PET segmentation threshold of 1.5 liver mean SUV + two standard deviations with a minimum volume constraint of 0.5 mL was utilized (MIM Software, Inc., Cleveland OH, USA) with manual input as needed. Functional splines analysis determined SUVmax and TMTV threshold for analysis. Results: 131 patients had complete PET-CT data (N=79 prDLBCL, N=52 erDLBCL). Baseline median TMTV and SUVmax were 767.4 cm3 (range 0.9-6840.4) and 20.5 (2.0-52.6), respectively. At a median follow up of 77.6 months, 81 patients had died. 2-year OS rate was 53% (95% CI: 42-67) for patients with a PET2 ΔSUVmax decline ≥65% compared to 15% (95% CI: 7-29) for patients with a PET2 ΔSUVmax decline &lt;65%(p&lt;0.001). PrDLBCL had a 2-year OS rate of 48% (95% CI: 31-74) for a ΔSUVmax ≥65% compared to 7% (95% CI: 2-21) for a ΔSUVmax &lt;65%(p&lt;0.001), which captured 58% of prDLBCL patients (N=46). Two-year OS rate was 43% (95% CI: 34-54) for patients with a ΔTMTV ≥75% compared to 5% (95% CI: 1-35) for patients with ΔTMTV &lt;75% (p&lt;0.001). All patients with a ΔTMTV &lt;75% had prDLBCL. PrDLBCL had a 2-year OS rate of 28% (95% CI: 18-44) for a ΔTMTV ≥75%. The outcomes for ΔSUVmax &lt;65% and ΔTMTV &lt;75% at PET2 remained significant in a cox regression model adjusted for IPI and bulky disease (&gt;10cm)(Table). Conclusions: A ΔTMTV decline &lt;75% or a ΔSUVmax decline &lt;65% at PET2 identified an ultra-high-risk subgroup of DLBCL with particularly poor outcomes, that captured a high percentage of prDLBCL patients, and was significant after adjusting for IPI and bulky baseline disease. These patients may benefit from clinical trials evaluating alternative PET-adapted treatment strategies, but further evaluation among all patients with DLBCL is needed. [Table: see text]

Early changes of PSMA PET signal after initiation of androgen receptor signaling inhibitors in mCRPC: An international multicenter retrospective study.

5063 Background: Androgen receptor signaling inhibitors (ARSi) play a relevant role in the treatment of prostate cancer. A potential influence of ARSi on PSMA expression has been described. We evaluated early changes of PSMA-expression by PET in mCRPC patients. Methods: This retrospective study included 5 international sites. Patients with mCRPC undergoing 68Ga-PSMA-11 PET/CT prior to (PET1) and early after ARSi (PET2 within 29 days maximum) were included. Whole-body (WB) PSMA-positive tumor volume (PSMA-TV) was evaluated using a liver-specific semi-automatically threshold (Affinity 3.0.2, Hermes Medical Solutions). WB PSMA-TV, SUVmean and SUVmax and their respective changes (%) were analyzed. PSA changes between PET 1 and PET2 were evaluated. Median values and ranges are provided. Results: 54 patients were included in the analysis. ARSi was initiated 1 day (range 0 – 28) after PET1 while PET2 was performed 14 days (range 7 – 29) after ARSi initiation. PSA at PET1 and PET2 was 9.5 ng/ml (range 0.2 – 490.0) and 8.7 ng/ml (range 0.1 – 732.0), respectively (p = 0.035): -33.0% (range -98% – +496%). The WB PSMA-TV at PET1 and PET2 was 89.9 ml (0.0 – 3097.0) and 112.2 ml (0.0 – 3133.0) ml, respectively (p = 0.016; change of +6.0% (range -88% – +260%). WB PSMA SUVmean and SUVmax at PET1 and PET2 was 9.0 (range 5.0 – 43.7) and 9.3 (range 0.0 – 42.5) and 26.5 (range 0.0 – 125.0) and 28.5 (range 0.0 – 212.0), respectively (p = 0.194 and p = 0.353): % change of +3 % (-85% – +71%) and 0% (-55% – +232%). Four of 7 patients with PSA increases at PET2 had an increasing PSMA-TV, 6/7 showed an increasing SUVmean and 5/7 presented with an increased SUVmax. Decreasing WB-PSMA-TV in 18/54 (33%) patients was accompanied by decreasing SUVs in 10 of them (56%). Percent PSA change was unrelated to changes in PSMA-TV, SUVmean and SUVmax. Conclusions: PSMA-PET performed early after ARSI revealed slight increases in the WB-PSMA-TV, stable WB-PSMA SUVs while serum PSA decreased in most of the patients. We conclude that ARSi does not have a strong effect on PSMA expression within 30 days after treatment initiation. [Table: see text]

Serial Quantitative Assessment of Load Redistribution After Medial Open-Wedge High Tibial Osteotomy.

The maximum standardized uptake value (SUVmax), as determined on combined single-photon emission computed tomography and conventional computed tomography (SPECT/CT), can be an indicator of biomechanical changes due to the load redistribution effect after medial open-wedge high tibial osteotomy (MOW-HTO). The purposes of this study were to (1) analyze serial changes in the SUVmax in the medial, lateral, and patellofemoral compartments after MOW-HTO and (2) identify the contributing factors that affect changes in the SUVmax. The hypotheses were that (1) an elevated SUVmax in the medial compartment would be transferred to the lateral compartment because of the load redistribution effect and (2) there would be contributing factors that cause SUVmax changes. Case series; Level of evidence, 4. Included were 67 knees that were treated with biplanar MOW-HTO between March 2019 and December 2020. SPECT/CT was performed immediately after surgery and at 3 months and 1 year postoperatively to determine the serial load redistribution effect of MOW-HTO. The Pearson correlation coefficient was used to evaluate the relationship between SUVmax and radiological parameters, and subgroup analyses were conducted to compare the SUVmax according to associated cartilage procedures and the weightbearing line ratio (WBLR). The SUVmax in the medial and lateral compartments increased at 3 months but decreased at 1 year postoperatively. The load redistribution effect was most prominent in the anterior zones of the femur (medial: P = .041; lateral: P = .012). In the patella, the SUVmax decreased in both the medial and the lateral zones at all follow-up times (P < .001 for all). The SUVmax in the anterolateral and posterolateral articular zones of the femur increased with a greater preoperative WBLR (r = 0.256, P = .039; and r = 0.261, P = .036, respectively). Patients who underwent an associated cartilage procedure had a significantly higher SUVmax in the anteromedial and posteromedial articular zones of both the femur and the tibia at 1 year postoperatively (P ≤ .002 for all). After MOW-HTO, the unloading effect in the anteromedial articular zone of the femur was the most significant. A greater SUVmax in the lateral zones of the femur was observed in cases of overcorrection. The SUVmax in the medial zones was higher postoperatively in patients with associated cartilage procedures.

Usefulness of quantitative bone SPECT/CT for evaluating medication-related osteonecrosis of the jaw treatment response.

For assessment of therapeutic response in medication-related osteonecrosis of the jaw (MRONJ) cases, the clinical usefulness of quantitative bone single-photon computed tomography-computed tomography (SPECT/CT) results was investigated. Sixteen patients (18 lesions) with a clinical diagnosis of MRONJ underwent bone SPECT/CT scanning before and during/after anti-inflammatory therapy given for 3 or more months. The GI-BONE software package was used to determine standard uptake values (SUVs), including maximum (SUVmax), peak (SUVpeak), and mean (SUVmean), and metabolic bone volume (MBV) and also total bone uptake (TBU). In both responders (downstage) and non-responders (upstage or no change), differences in quantitative values between the first and second SPECT/CT examinations were analyzed using a Wilcoxon test. Following therapy, significant reductions in SUVmax, SUVpeak, SUVmean, MBV and TBU values for 11 lesions were noted in the responders after therapy (p = 0.003, p = 0.006, p = 0.004, p = 0.003, and p = 0.002, respectively). On the other hand, those for the seven lesions in the non-responder group were not significantly different (p = 0.17, p = 0.16, p = 0.26, p = 0.96, and p = 0.12, respectively). Results for SUVmax change showed sensitivity and specificity values of 45.5% and 85.7%, respectively, for differentiating responders from non-responders, with -37.3% the optimal cutoff value. Those for MBV change were 72.7 and 85.7%, respectively, with -29.4% the optimal cutoff value. Those for TBU change were 81.8% and 85.7%, respectively, with -36.3% the optimal cutoff value. The present findings showed that therapeutic response in MRONJ cases could be determined by use of quantitative SUV, MBV, and TBU values based on bone SPECT/CT findings.

EVALUATION OF METABOLIC RESPONSE IN BONE MARROW LESIONS AFTER EXERCISE IN RELATION TO CHANGES IN ADJACENT CARTILAGE T2 VALUES

Patellofemoral pain syndrome (PFPS) is one of the most common causes of anterior knee pain in active populations. Due to its multifactorial nature, patellofemoral pain is hard to diagnose and treat. Increased stress in the subchondral bone is associated with PFPS and is correlated to elevated bone remodelling. [18F]NaF PET-MR imaging can localize regions of elevated bone remodelling and provide information about the metabolic processes involved (1, 2). Further, [18F]NaF uptake changes after exercise, thus showing that it is sensitive to changes in bone physiology resulting from acute bone loading (3, 4). For cartilage, T2 relaxation times have been used to study cartilage hydration and microstructure changes after exercise. While some studies have observed a decrease in T2 times after exercise, changes are usually transient and have largely been evaluated in the context of healthy subjects (5). An early sign of persistent abnormal mechanical stress is Bone Marrow Lesions (BMLs), which are strongly associated with pain and structural disease progression. We aimed to reproduce prior work which has shown that acute loading results in a large physiological response in bone regions with BMLs. Further, we wanted to explore if there is breakdown of the cartilage microstructure, either at baseline or in response to loading in cartilage regions adjacent to BMLs. The purpose of this study is to detect changes in the functional response of the knee joint to loading using [18F]NaF PET-MR imaging after a stair-climbing exercise in subjects with unilateral patellofemoral pain. The aims of this feasibility study are 1) to detect acute loading-induced changes in [18F]NaF uptake in bone regions with BMLs and 2) compare consequent T2 values in the cartilage adjacent to BMLs at baseline and in response to loading. 4 subjects (3 F, aged 39.5±15.0 years, BMI 26.1±5.9 kg/m2) with unilateral knee pain and BMLs (3 in patella, 1 in femur) underwent two consecutive 30-min [18F]NaF PET/MRI scans of both knees, at baseline and then repeated after a stair-climbing exercise [112 stairs, up and down]. Bone metabolic activity was quantified by calculating maximum standardized uptake values (SUVmax) in areas of BMLs in the painful leg and the corresponding region in the contralateral leg. T2 maps were calculated from quantitative DESS images [TE(1,2)=6.04, 30.44 ms] in the cartilage regions adjacent to the BMLs and in the same regions in the contralateral leg. Segmentations of cartilage were done manually in MATLAB, while SUVmax in BMLs was calculated using ROIs drawn in Horos. Pre- and post-exercise changes in SUVmax and T2 values were compared to account for loading-induced response in both metabolic and structural parameters in painful vs healthy knees. Increased [18F]NaF uptake was observed post-exercise in areas with BMLs (as compared to contralateral leg regions), confirming that PET findings correspond to structural changes observed in MRI (Fig-1). The average SUVmax values increased from 6.35±3.98 to 10.49±5.42 in the painful leg and from 1.71±1.96 to 4.04±3.21 in the contralateral leg after exercise. The average T2 relaxation times increased from 30.61±1.87 ms to 31.61±1.55 ms in the painful leg and from 27.17±2.73 ms to 27.65±2.29 ms in the contralateral leg (Fig-2). The mean change in SUVmax due to exercise was 4.15±2.42 in the BML vs 2.34±2.06 in the contralateral leg. In adjacent cartilage, a mean change in T2 values of 1.01±1.45 ms in the BML region of the painful leg and 0.47±0.48 ms in the contralateral leg was observed. In this feasibility study, [18F]NaF PET-MR showed acute loading-induced changes in BMLs, with a 2-fold increase in SUVmax in the painful leg vs the contralateral leg. While there seemed to be a higher cartilage T2 in regions adjacent to BMLs compared to the contralateral leg, the change induced by exercise was small.

Quantification of bone metabolic activity in the natural course of fractural lesions measured by quantitative SPECT/CT.

While increased uptake at the bone fractural site gradually decreases over time on bone scans, the rate of change has not been quantitatively evaluated. The purpose of this study was to quantify the extent of bone metabolic changes in fractural lesions on bone SPECT/CT. We reviewed bone scans acquired by dedicated SPECT/CT and chose those scans in which quantitative SPECT/CT of the same range was acquired twice or more. We set the region of interest on lesions of bone fracture and degeneration, and measured the maximum standardized uptake value (SUVmax). From the SUVmax of lesions and the interval between scans, a value for 30-day change in SUVmax was calculated as ∆SUVmax30d. The relationship between preSUVmax, SUVmax for the first scan of the comparison, and ∆SUVmax30d was evaluated utilizing a linear least-squares method. Furthermore, we assessed the ability to differentiate between fracture and degeneration using receiver operating characteristics (ROC) analysis and the Mann-Whitney U test. All cases were then categorized into five groups according to preSUVmax. Values of p <0.05 were considered statistically significant. We investigated 175 scans from 60 patients and analyzed scan combinations for 157 fractural lesions and 266 degenerative lesions. The relationship between preSUVmax of fractural lesions and ∆SUVmax30d was approximated as ∆SUVmax30d =-0.15×preSUVmax +1.35 (R 2=0.60, p<0.0001). Area under the curves for all cases, 30≤ preSUVmax, 20≤ preSUVmax <30, 15≤ preSUVmax <20, 10≤ preSUVmax <15, and preSUVmax <10 were 0.73, 0.89, 0.86, 0.80, 0.91, and 0.59, respectively. Median ∆SUVmax30d was significantly lower at fractural lesions than at degenerative lesions (-0.62 vs -0.04; p <0.0001). As for analyses of groups divided by preSUVmax, all median ∆SUVmax30d for fractural lesions were significantly lower than those of degenerative lesions except for the group with preSUVmax <10. The increased uptake at the fractural bone lesion observed in the quantitative bone SPECT/CT gradually decreased at the rate of SUV 0.15 per month, which showed a different trend with degenerative change.

NI-16 RESPONSE ASSESSMENT OF BEVACIZUMAB THERAPY FOR GLIOBLASTOMA BY USING MULTIPLE PET TRACERS

Abstract Objective PET scans are useful for the diagnosis and treatment planning of glioma. Introduced in 2013, bevacizumab (Bev) treatment efficacy can be difficult to determine using MRI imaging. We instead performed PET scans to determine the efficacy of Bev-based glioblastoma treatment. Methods Eighty glioblastoma patients treated with Bev from July 2013 to December 2021 were included. The patients were divided into the following three groups: the first group received Bev added to the Stupp regimen after biopsy or subtotal resection (first-dose group), the second group received Bev added to the Stupp regimen after biopsy followed by tumor resection (neoadjuvant group), and the third group received the Stupp regimen after tumor resection followed by TMZ + Bev at recurrence (recurrent group). PET scans (FDG, MET, FLT, and FMISO) were performed before and 4 weeks after the start of the Bev treatment. FDG, MET, and FLT measured tumor-to-normal ratio (TNR), and FMISO measured tumor-to-blood ratio (TBR), as well as the percent change in SUVmax, TNR, TBR, and MTV before and after Bev treatment. Using the Cox proportional hazards model, we examined which of these rates of change were the prognostic factors. Results The median PFS (months) and median OS from Bev treatment were 8.87, 16.53, and 4.0 and 12.53, 22.13, and 8.0, respectively. Significant differences in the percent change in MTV for MET, FLT, and FMISO in the first-line group, the percent change in MTV for FDG and MET, the percent change in FDG TNR and FMISO TBR in the recurrent group, and the percent change in MTV for MET and FLT in the neoadjuvant group were shown in the Cox proportional hazards model. Conclusion Neoadjuvant treatment with Bev prolonged PFS and OS. The decrease in MET MTV change rate and FMISO TBR.

Longitudinal monitoring of fetlock lesions in Thoroughbred racehorses using standing 18F-sodium fluoride positron emission tomography.

To assess the repeatability of equine 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings, and to evaluate the ability of PET to monitor the progression of areas of increased radiopharmaceutical uptake (IRU) in the fetlocks of Thoroughbred racehorses. 25 racehorses with clinical signs related to fetlock injuries. This study is a prospective, longitudinal clinical study. Twenty-five racehorses (54 fetlocks) underwent three 18F-NaF PET scans 6 weeks apart. The first 18F-NaF PET scan was performed at the start of a 12-week period of rest from racing (lay-up). Areas of IRU in the fetlock joints were quantified using maximal standardized uptake values (SUVmax) and were graded by 2 experienced observers. Statistical comparisons were made between scans to detect changes in IRU grade and SUVmax over time. Standing PET findings were repeatable, with 131/149 (88%) areas of IRU identified on the initial scans seen again at the 6-week follow-up scan. The palmar/plantar condyles were the sites most commonly presenting with IRU, followed by the proximal sesamoid bones. Overall, 65% of fetlocks demonstrated improvement in IRU grade during the 12-week period of rest from racing. Areas of higher IRU grade took longer to resolve than the lower graded areas. Standing PET findings in the racehorse fetlock were repeatable. The SUV-based grading system may be helpful when determining appropriate lay-up duration for Thoroughbred racehorses. PET may be used to monitor areas of the fetlock involved in catastrophic breakdown injuries in Thoroughbred racehorses.

Reliability of gradient-based segmentation for measuring metabolic parameters influenced by uptake time on 18F-PSMA-1007 PET/CT for prostate cancer.

PurposeTo determine an optimal setting for functional contouring and quantification of prostate cancer lesions with minimal variation by evaluating metabolic parameters on 18F-PSMA-1007 PET/CT measured by threshold-based and gradient-based methods under the influence of varying uptake time.Methods and materialsDual time point PET/CT was chosen to mimic varying uptake time in clinical setting. Positive lesions of patients who presented with newly diagnosed disease or biochemical recurrence after total prostatectomy were reviewed retrospectively. Gradient-based and threshold-based tools at 40%, 50% and 60% of lesion SUVmax (MIM 6.9) were used to create contours on PET. Contouring was considered completed if the target lesion, with its hottest voxel, was delineated from background tissues and nearby lesions under criteria specific to their operations. The changes in functional tumour volume (FTV) and metabolic tumour burden (MTB, defined as the product of SUVmean and FTV) were analysed. Lesion uptake patterns (increase/decrease/stable) were determined by the percentage change in tumour SUVmax at ±10% limit.ResultsA total of 275 lesions (135 intra-prostatic lesions, 65 lymph nodes, 45 bone lesions and 30 soft tissue lesions in pelvic region) in 68 patients were included. Mean uptake time of early and delayed imaging were 94 and 144 minutes respectively. Threshold-based method using 40% to 60% delineated only 85 (31%), 110 (40%) and 137 (50%) of lesions which all were contoured by gradient-based method. Although the overall percentage change using threshold at 50% was the smallest among other threshold levels in FTV measurement, it was still larger than gradient-based method (median: 50%=-7.6% vs gradient=0%). The overall percentage increase in MTB of gradient-based method (median: 6.3%) was compatible with the increase in tumour SUVmax. Only a small proportion of intra-prostatic lesions (<2%), LN (<4%), bone lesions (0%) and soft tissue lesions (<4%) demonstrated decrease uptake patterns.ConclusionsWith a high completion rate, gradient-based method is reliable for prostate cancer lesion contouring on 18F-PSMA-1007 PET/CT. Under the influence of varying uptake time, it has smaller variation than threshold-based method for measuring volumetric parameters. Therefore, gradient-based method is recommended for tumour delineation and quantification on 18F-PSMA-1007 PET/CT.

Potential value of pre- and post-therapy [68Ga]Ga-DOTA-TATE PET/CT in the prognosis of response to PRRT in disseminated neuroendocrine tumors.

BackgroundPeptide receptor radionuclide therapy (PRRT) is one of the most effective therapeutic options for the treatment of metastatic, well-differentiated neuroendocrine tumors (NETs). It improves progressive disease-free survival and enables the control of hormone secretion in functioning tumors.Currently, there are no clearly established predictors of response to PRRT. The main factors hindering such a prediction are the heterogeneity of somatostatin receptor expression within and between lesions, lack of standardized parameters for functional imaging, and the use of different PRRT protocols.The main goal of our study was to quantify SUVmax changes in [68Ga]Ga-DOTA-TATE PET/CT scans as a potential predictor of long-term response to PRRT.Material and methodsOut of 20 patients treated with PRRT using [177Lu]Lu and/or [177Lu]Lu/[90Y]Y-DOTA-TATE in 2017–2019 due to dissemination of neuroendocrine neoplasm, 12 patients underwent [68Ga]Ga-DOTA-TATE PET/CT on average 3.1 months before and 4.5 months after PRRT and were eligible for the analysis.In total, 76 NET lesions were evaluated. We measured SUVmax for every lesion in both PET/CT scans (before and after PRRT). Those values were corrected by liver SUVmax and liver SUVmean measured in volumetric analysis and specified as SUVlmax and SUVlmean. As a next step, changes in SUVlmax and SUVlmean were assessed based on both PET/CT scans. Finally, results were correlated with the clinical outcome assessed as progressive disease, disease stabilization, or partial response.ResultsThe mean follow-up period was 19.9 months. Progressive disease, partial response, and disease stabilization were found in five, two, and five patients, respectively. Among patients with a partial response, the decrease in mean SUVlmax was 66.3% when compared to baseline. In patients with stable disease, the decrease in SUVlmax was 30.3% when compared to baseline. In patients with progressive disease, the mean increase in SUVlmax was 9.1% when compared to baseline. The changes in SUVlmean were -69,8%, -30.8%, and -3.7%, respectively.ConclusionsA decrease in the SUVmax value in NET lesions, corrected by normal liver tissue uptake assessed in [68Ga]Ga-DOTA-TATE PET/CT scans, indicates a lower risk for NET progressive disease within 20 months after PRRT and may constitute an additional and independent parameter for the estimation of overall risk for disease progression.

Dynamic 18 F-FDG PET/CT can predict the major pathological response to neoadjuvant immunotherapy in non-small cell lung cancer.

Major pathological response (MPR) is a potential surrogate for overall survival. We determined whether the dynamic changes in 18F‐labeled fluoro‐2‐deoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) were associated with MPR in patients receiving neoadjuvant immunotherapy. Forty‐four patients with stage II–III non‐small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy and radical surgery were enrolled. Moreover, 18F‐FDG PET/CT scans were performed at baseline and within 1 week before surgery to evaluate the disease. All histological sections were reviewed to assess MPR. The detailed clinical features of the patients were analyzed. The reliability of the clinical variables was assessed in differentiating between MPR and non‐MPR using logistic regression. Receiver‐operating characteristic (ROC) curve analysis identified the SUVmax changes threshold most associated with MPR. Most of the patients were pathologically diagnosed with squamous cell carcinoma and received anti‐PD‐1 antibodies plus chemotherapy. The immunotherapy regimens included nivolumab, pembrolizumab, and camrelizumab. MPR was observed in more than half of lesions. Tumors with MPR had a higher decrease in the longest dimension on dynamic PET/CT than those without MPR. Furthermore, the decline in SUVmax was significantly different between MPR and non‐MPR diseases, and MPR lesions had a prominent mean reduction in SUVmax. SUVmax reduction was independently associated with MPR in the multivariate regression. On ROC analysis, the threshold of SUVmax decrease in 60% was associated with MPR. Dynamic changes in SUVmax were associated with MPR. The tumors with MPR showed a greater PET/CT response than those without MPR. A SUVmax decrease of more than 60% is more likely to result in an MPR after receiving neoadjuvant immunotherapy.

Sequential Imaging Characteristics and Potential Role of F18 Fluorodeoxyglucose Positron Emission Tomography/CT in the Evaluation of Treatment Response in Cases of Spinal Tuberculosis Without Neurological Involvement: Results From a Pilot Study.

PurposeIn this non-randomized study, we prospectively studied the sequential imaging properties of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and evaluated the role of FDG PET as a non-invasive imaging modality for identifying non-responders during anti-tubercular treatment (ATT) of spinal tuberculosis (TB).MethodsBefore starting anti-tubercular treatment, 25 patients with clinically and radiological suspected; pathologically confirmed spinal TB had a pretreatment contrast-enhanced whole-body FDG PET scan, followed by scans at six, 12, and 18 months. The maximum standardized uptake value (SUVmax) was computed, and the mean change in SUVmax was compared. The mean change in SUVmax was correlated with the clinicoradiological improvement. ResultIn cases of spinal tuberculosis, the FDG PET scan can help identify extra-spinal and non-contagious involvement. In our 25 cases of spinal TB, the baseline peak SUVmax of lesions ranged from 6.3 to 28.5 (mean 14.8). Despite treatment, the condition progressed in two patients, and they had neurological deficits; in both cases, the SUVmax levels increased. The fall in SUVmax during the treatment course was statistically significant (p-value <0.05) and correlated well with the clinical improvement.ConclusionThe inflammatory cells show increased uptake of F18 FDG, so uptake of radioactive tracer localizes and quantifies the disease activity; thus, FDG PET/CT holds a promising role as a sensitive non-invasive modality for the detection, staging, assessing disease activity, and monitoring therapy and deciding end point treatment in spinal TB.

Gadolinium-based contrast agent attenuation does not impact PET quantification in simultaneous dynamic contrast enhanced breast PET/MR.

Simultaneous PET/MR imaging involves injection of a radiopharmaceutical and often also includes administration of a gadolinium-based contrast agent (GBCA). Phantom model studies indicate that attenuation of annihilation photons by GBCAs does not bias quantification metrics of PET radiopharmaceutical uptake. However, a direct comparison of attenuation-corrected PET values before and after administration of GBCA has not been performed in patients imaged with simultaneous dynamic PET/MR. The purpose of this study was to investigate the attenuating effect of GBCAs on standardized uptake value (SUV) quantification of 18 F-fluorodeoxyglucose (FDG) uptake in invasive breast cancer and normal tissues using simultaneous PET/MR. The study included 13 women with newly diagnosed invasive breast cancer imaged using simultaneous dedicated prone breast PET/MR with FDG. PET data collection and two-point Dixon-based MR attenuation correction sequences began simultaneously before the administration of GBCA to avoid a potential impact of GBCA on the attenuation correction map. A standard clinical dose of GBCA was intravenously administered for the dynamic contrast enhanced MR sequences obtained during the simultaneous PET data acquisition. PET data were dynamically reconstructed into 60 frames of 30 s each. Three timing windows were chosen consisting of a single frame (30 s), two frames (60 s), or four frames (120 s) immediately before and after contrast administration. SUVmax and SUVmean of the biopsy-proven breast malignancy, fibroglandular tissue of the contralateral normal breast, descending aorta, and liver were calculated prior to and following GBCA administration. Percent change in the SUV metrics were calculated to test for a statistically significant, non-zero percent change using Wilcoxon signed-rank tests. No statistical change in SUVmax or SUVmean was found for the breast malignancies or normal anatomical regions during the timing windows before and after GBCA administration. GBCAs do not significantly impact the results of PET quantification by means of additional attenuation. However, GBCAs may still affect quantification by affecting MR acquisitions used for MR-based attenuation correction which this study did not address. Corrections to account for attenuation due to clinical concentrations of GBCAs are not necessary in simultaneous PET/MR examinations when MR-based attenuation correction sequences are performed prior to GBCA administration.

Assessing PD-L1 without a biopsy and through PD-L1 PET imaging with 18F-BMS-986229.

2578 Background: Programmed death ligand-1 (PD-L1) is usually determined by immunohistochemistry (IHC). Determining PD-L1 status by whole body, non-invasive PD-L1 PET imaging with 18F-BMS-986229 tracer infusion may be a way to circumvent limitations to PD-L1 IHC such as poor tissue availability; discrepant PD-L1 IHC results among different tumors within the same patient; and inability to measure PD-L1 longitudinally given challenges with repeated biopsies. Methods: Within the prospective ADAPT-IT trial (NCT03122522) testing an abbreviated course of nivolumab (nivo) + ipilimumab (ipi) in patients with unresectable stage III or IV melanoma, we investigated PD-L1 PET imaging in a 10-patient expansion cohort at baseline and after 6 weeks of treatment. Maximum standard uptake value (SUV max) and mean of all SUV max for lesions for PD-L1 PET were calculated on a whole patient level for each target/ non target lesion. Standard treatment response was determined by RECIST v1.1 at weeks 6 and 12. PD-L1 IHC was scored using the E1L3N antibody by tumor proportion score (TPS), Immune Cell Score (ICS), and a Combined Positive Score (CPS). Comparisons between PD-L1 PET parameters and response were determined by complete or partial response (CR/PR); stable disease (SD), and progressive disease (PD) at respective imaging timepoints. Absolute changes in PD-L1 SUV mean and max were calculated between scans. The correlation between PD-L1 PET and IHC was estimated using Spearman’s coefficient correlation. Results: Five patients (50%) had a PR to treatment at week 6; one of these PR became a CR at week 12 and one PR was not assessable at week 12. All RECIST responders at week 6 (n = 5) had baseline PD-L1 SUV mean ≥3.00, and all progressors at week 6 (n = 3) had baseline PD-L1 SUV mean ≤2.60 (Table). A similar trend was observed when assessing response at week 12 and when considering baseline PD-L1 SUV max. Patients had changes in their PD-L1 SUV levels between baseline and week 6. Baseline PD-L1 SUV mean (inclusive of all lesions within a patient) correlated with PD-L1 IHC by TPS, ICS, and CPS (r = 0.64, 0.5, 0.47, respectively). No patients had side effects from 18F-BMS-986229 tracer infusion. Conclusions: The signal of PD-L1 positivity by PET imaging with 18F-BMS-986229 at baseline appears associated with early efficacy from nivo + ipi in this small cohort and may offer additional information than PD-L1 IHC. The ability to assess PD-L1 on a whole patient level at multiple timepoints on treatment may have future implications in how best to sequence and combine immunotherapies but further study in larger patient cohorts is needed. Clinical trial information: NCT03122522. [Table: see text]

Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients with Low and Intermediate Risk p16-positive Oropharynx Cancers

<h3>Purpose/Objective(s)</h3> To compare the intratreatment PET/MRI tumor response in patients with low-risk (LR) and intermediate-risk (IR) p16-positive oropharynx cancer during chemoradiotherapy. <h3>Materials/Methods</h3> Patients with non-metastatic, p16-positive oropharynx cancer were treated with definitive chemoradiotherapy. LR disease was defined as cT0-3 and cN0-2b and </= 10 pack-years and IR disease as cT4 or cN2b-3 or > 10 pack-years. Patients underwent a PET/MRI scan pre-treatment and at fraction 10. PET/MRI data used for analysis of the primary tumor and largest node included changes in volume, SUVmax, SUVmedian, SUVpeak, and diffusion. Radiographic differences between LR and IR patients were compared using the standard t-test. Principal component analysis, with K-means and Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters similarity of objects within each cluster. Linear regression was performed on all radiographic metrics using patient and disease characteristics. <h3>Results</h3> Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Cluster analysis defined two cohorts that exhibited a similar intratreatment response. Cohort 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cohort 2 contained 3 of 11 IR patients. There was a trend for patients in Cohort 2 to be older (mean 68 years ± 5 versus 59 years ± 7; p = 0.057) and have a higher smoking history (mean 30 pack-years ± 40 s.d. versus 12 pack-years ± 17 s.d.; p = 0.2). Cluster 2 exhibited significant differences compared to cluster 1 in the change in primary tumor SUVpeak (0.46 mean ± 0.15 s.d. versus -0.22 mean ± 0.24 s.d.; p < 0.001) and largest lymph node SUVmedian (0.43 mean ± 0. s.d. versus -0.00 mean ± 0.9 s.d.; p = 0.001) after 10 fractions of chemoradiotherapy. <h3>Conclusion</h3> We demonstrate that intermediate-risk p16-positive oropharynx cancers exhibit heterogeneity in their radiographic response to chemoradiotherapy. These data support further study of intratreatment image response as a mechanism for identifying patients with intermediate-risk disease suitable for therapy de-intensification.