Cerebellum/liver index on baseline 18F-FDG PET/CT to improve prognostication in post-transplant lymphoproliferative disorders: a multicenter retrospective study.

BACKGROUND: Besides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses. RESULTS: A total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0-4.0) and 2.4 (1.3-4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 (p = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS. CONCLUSION: CLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.

Outcome on Mesenteric Mass Response of Small-Intestinal Neuroendocrine Tumors Treated by 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: The MesenLuth Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.

A mesenteric mass (MM), characterized by fibrotic reaction, is present in most small-intestinal neuroendocrine tumors (SI-NETs). 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) has shown its efficacy in patients with progressive SI-NETs. However, because of specific tissue characteristics of desmoplastic MMs, we hypothesize that these lesions may be refractory to 177Lu-DOTATATE PRRT. Methods: From the national French Groupe d'étude des Tumeurs Endocrines database, we identified patients with an advanced SI-NET and a MM (≥2 cm with a retractile aspect) of a SI-NET treated by at least 1 course of 177Lu-DOTATATE PRRT. The primary endpoint was a MM objective response rate (ORR) of less than 5%. Secondary endpoints were metabolic response, MM-related safety, and clinical response, as well as MM progression-free survival (PFS) and non-MM PFS. Results: In total, 52 patients were included. The MM ORR was 4% (n = 2), and the non-MM ORR was 8% (n = 4). No patient had a MM metabolic response, and the non-MM metabolic response rate was 12% (n = 6). Among the 26 patients with baseline MM-related symptoms, 46% had a clinical response. Four patients presented with gastrointestinal complications during PRRT. The median MM-related PFS was not reached, and the non-MM PFS was 50.3 mo (95% CI, 38.2-61.7 mo). Conclusion: This study confirms that 177Lu-DOTATATE PRRT does not lead to morphologic response on MMs (ORR < 5%). However, it allows MM stability, with few MM-related side effects, and has a relevant impact on MM-related symptoms.

Determinants of the uptake of the uncinate process of pancreas in 68Ga-DOTATOC PET/CT: a retrospective study.

PURPOSE: an increased uptake of the uncinate process of pancreas (UPP) has been described in about one-third of somatostatin receptor imaging procedures and may hinder image interpretation. The determinants of this uptake are however poorly understood. The aim of this study was to investigate the impact of cold somatostatin analogues (cSA) on UPP 68Ga-DOTATOC uptake. Age and diabetic status were also studied. METHODS: all adult patients who performed a 68Ga-DOTATOC PET/CT in our center between May 2021 and April 2023 were retrospectively screened. For each one, UPP uptake was visually assessed and measured using SUVmax. Clinical data including cSA medication, age and diabetic status were collected. Univariate and multivariate analyses were conducted using logistic regression. SUVmax comparisons were conducted using a Mann-Whitney Wilcoxon test. RESULTS: 82 patients were included. UPP uptake was significantly lower in patients treated with cSA (OR 0.27, p = 0.015 in multivariate analysis), with a lower SUVmax (4.97 vs. 8.81, p = 0.001). No significant result was found regarding diabetic status or age. CONCLUSION: cold somatostatin analog treatment decreased the physiological UPP uptake in 68Ga-DOTATOC PET/CT. This effect could be used to reduce interpretation errors in this location.

Added value of early-phase SPECT over planar acquisition in bone imaging.

BACKGROUND: The aim of this study is to evaluate the added value of early bone single photon emission computed tomography (SPECT) by comparison to pseudoplanar imaging. METHODS: Fifty patients were retrospectively included from 3 centers. Reading sessions were organized using: late-phase acquisition alone; early SPECT and late-phase acquisition; early pseudoplanar and late-phase acquisition. The comparison between early SPECT and MIP was performed using a McNemar Test. Patients for whom early SPECT had provided additional information were also compared with patients for whom early SPECT had not. RESULTS: Fifty patients were included. Early SPECT was superior to pseudoplanar MIP in 10/50 patients (20.0%, P=0.044). No significant difference was found between this group and the remainder. Early SPECT changed the diagnosis established from late-phase imaging in 21/50 patients. CONCLUSIONS: Early SPECT is a promising tool in bone imaging and change the diagnosis in one fifth of the cases by comparison to pseudoplanar imaging.

High Tumor Uptake on 18F-FDOPA PET/CT Indicates Poor Prognosis in Patients with Metastatic Midgut Neuroendocrine Tumors: A Study from the Groupe d'étude des Tumeurs Endocrines and ENDOCAN-RENATEN Network.

PET/CT with 6-18F-fluoro-l-dopa (18F-FDOPA) has high diagnostic performance for midgut neuroendocrine tumors (NETs). We explored the prognostic role of 18F-FDOPA PET/CT uptake in metastatic midgut NETs. Methods: We included, in a test cohort (n = 166) and a full external validation cohort (n = 86), all consecutive patients with metastatic midgut NETs who underwent 18F-FDOPA PET/CT in 5 expert centers from 2010 to 2021. We measured the maximal uptake (SUVmax and SUVpeak) of the tumor and nontumor liver on each 18F-FDOPA PET/CT scan. We measured overall survival (OS) from the time of PET/CT and assessed prognostic factors using Kaplan-Meier and multivariable Cox proportional-hazards analyses in the test cohort, with replication in the validation cohort. Results: Patients had similar characteristics in both cohorts. In the test cohort, median follow-up was 60.3 mo. Patients with an SUVpeak tumor-to-liver (T/L) ratio of more than 4.2 had significantly shorter survival than those with a ratio of 4.2 or less (P = 0.01), with a 5-y OS rate of 74.1% ± 4.5% versus 95% ± 3.4%, respectively. On multivariable analysis, an SUVpeak T/L ratio of more than 4.2 remained associated with shorter OS (hazard ratio, 2.30; 95% CI, 1.02-5.22; P = 0.046) after adjustment for age, grade, number of previous lines, number of metastatic sites, and presence of carcinoid syndrome. In the validation cohort, the 5-y OS rate was 100% versus 57.8% ± 12.5% in patients with an SUVpeak T/L ratio ≤ 4.2 or > 4.2, respectively (P = 0.075). An increasing SUVpeak T/L ratio over time tended to have a pejorative prognostic impact. Conclusion: Tumor uptake on 18F-FDOPA PET/CT is an independent prognostic factor in patients with metastatic midgut NETs.

Pretreatment CT Texture Parameters as Predictive Biomarkers of Progression-Free Survival in Follicular Lymphoma Treated with Immunochemotherapy and Rituximab Maintenance.

The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness values above -0.015 at SSF = 2 were significantly associated with lower PFS, PFS 24, and TTNT. Kurtosis without filtration was an independent predictor of PFS (SSF = 0; HR = 1.22 (95% CI: 1.04, 1.44), p = 0.013), and TTNT (SSF = 0; hazard ratio = 1.23; 95% CI: 1.04, 1.46; p = 0.013). This study shows that pretreatment unenhanced CT texture analysis-derived tumor skewness and kurtosis may be used as predictive biomarkers of PFS and TTNT in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance.

Implementation of xSPECT, xSPECT bone and Broadquant from literature, clinical survey and innovative phantom study with task-based image quality assessment.

OBJECTIVE: From patient and phantom studies, we aimed to highlight an original implementation process and share a two-years experience clinical feedback on xSPECT (xS), xSPECT Bone (xB) and Broadquant quantification (Siemens) for 99mTc-bone and 177Lu-NET (neuroendocrine tumors) imaging. METHODS: Firstly, we checked the relevance of implemented protocols and Broadquant module on the basis of literature and with a homogeneous phantom study respectively. Then, we described xS and xB behaviours with reconstruction parameters (10i-0mm to 40i-20mm) and optimized the protocols through a blinded survey (7 physicians). Finally, the preferred 99mTc-bone reconstruction was assessed through an IEC NEMA phantom including liquid bone spheres. Conventional SNR, CNR, spatial resolution, Q.%error, and recovery curves; and innovative NPS, TTF and detectability score d' were performed (ImQuest software). We also sought to review the adoption of these tools in clinical routine and showed the potential of quantitative xB in the context of theranostics (Xofigo®). RESULTS: We showed the need of optimization of implemented reconstruction algorithms and pointed out a decay correction particularity with Broadquant. Preferred parameters were 1s-25i-8mm and 1s-25i-5mm for xS/xB-bone and xS-NET imaging respectively. The phantom study highlighted the different image quality especially for the enhanced spatial resolution xB algorithm (1/TTF10%=2.1 mm) and showed F3D and xB shared the best performances in terms of image quality and quantification. xS was generally less efficient. CONCLUSIONS: Qualitative F3D still remains the clinical standard, xB and Broadquant offer challenging perspectives in theranostics. We introduced the potential of innovative metrics for image quality analysis and showed how CT tools should be adapted to fit nuclear medicine imaging.

Baseline 18F-FDG PET/CT Radiomics in Classical Hodgkin's Lymphoma: The Predictive Role of the Largest and the Hottest Lesions.

This study investigated the predictive role of baseline 18F-FDG PET/CT (bPET/CT) radiomics from two distinct target lesions in patients with classical Hodgkin's lymphoma (cHL). cHL patients examined with bPET/CT and interim PET/CT between 2010 and 2019 were retrospectively included. Two bPET/CT target lesions were selected for radiomic feature extraction: Lesion_A, with the largest axial diameter, and Lesion_B, with the highest SUVmax. Deauville score at interim PET/CT (DS) and 24-month progression-free-survival (PFS) were recorded. Mann-Whitney test identified the most promising image features (p < 0.05) from both lesions with regards to DS and PFS; all possible radiomic bivariate models were then built through a logistic regression analysis and trained/tested with a cross-fold validation test. The best bivariate models were selected based on their mean area under curve (mAUC). A total of 227 cHL patients were included. The best models for DS prediction had 0.78 ± 0.05 maximum mAUC, with a predominant contribution of Lesion_A features to the combinations. The best models for 24-month PFS prediction reached 0.74 ± 0.12 mAUC and mainly depended on Lesion_B features. bFDG-PET/CT radiomic features from the largest and hottest lesions in patients with cHL may provide relevant information in terms of early response-to-treatment and prognosis, thus representing an earlier and stronger decision-making support for therapeutic strategies. External validations of the proposed model are planned.

Impact of Cold Somatostatin Analog Administration on Somatostatin Receptor Imaging: A Systematic Review.

PURPOSE: The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is still advised as a precaution. The aim of this systematic review is to evaluate the consequences of cSA administration on tumoral and surrounding healthy organs' uptake at somatostatin receptor (SSTR) imaging with SPECT or PET. METHODS: After registration of the study on Prospero (CRD42022360260), an electronic search of PubMed and Scopus databases was performed. Inclusion criteria were as follows: human patients referred for SSTR imaging for oncological purposes; at least 1 examination performed either before cSA administration or after a long-enough withdrawal of cSA treatment; at least 1 examination was performed under cSA treatment. Included articles were independently appraised by 2 authors using the standardized protocol provided by the Quality Assessment of Diagnostic Accuracy Studies. Discrepancies were solved by consensus. RESULTS: A total of 12 articles were included, 4 using 111In-pentetreotide and 8 using 68Ga-DOTA peptides. Administration of cSAs consistently resulted in decreased spleen and liver uptake (from 6.9% to 80% for spleen, 10% to 60% for liver) and increased tumor-to-background or tumor-to-healthy organ ratios. After cSA treatment, tumor uptake alone was unchanged or moderately decreased. Similar results were noted whether patient was octreotide-naive. CONCLUSION: Impairment in SSTR imaging quality after cSA administration has not been demonstrated. On the contrary, the administration of cSAs seems to improve the contrast between tumoral lesions and the surroundings.

Risk Factors of Progression in Low-tumor Burden Follicular Lymphoma Initially Managed by Watch and Wait in the Era of PET and Rituximab.

Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1-3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed tomography (PET-CT), total metabolic tumor volume (TMTV) ≥14 cm3 and standardized Dmax (reflecting tumor dissemination) >0.32 m-1 were also associated with shorter TLT (HR = 3.4; P = 0.004 and HR = 2.4; P = 0.007, respectively). In multivariate models combining PET-CT parameters and clinical variables, TMTV remained independent predictor of shorter TLT. These simple parameters could help to identify FL patients initially observed at higher risk of early progression. The role of PET-CT (extranodal sites and PET metrics) in low-burden FL appears promising and warrants further assessment in large cohorts.

18F-FDG primary tumor uptake to improve N status prediction in cT1 non-metastatic non-small cell lung cancer: development and validation of a positron emission tomography model.

Purpose: Occult lymph node involvement is a major issue in the management of non-small cell lung carcinoma (NSCLC), with an estimated prevalence of approximately 2.9-21.6% in 18F-FDG PET/CT series. The aim of the study is to construct a PET model to improve lymph node assessment. Methods: Patients with a non-metastatic cT1 NSCLC were retrospectively included from two centers, one used to constitute the training set, the other for the validation set. The best multivariate model based on Akaike's information criterion was selected, considering age, sex, visual assessment of lymph node (cN0 status), lymph node SUVmax, primary tumor location, tumor size, and tumoral SUVmax (T_SUVmax). A threshold minimizing false pN0 prediction was chosen. This model was then applied to the validation set. Results: In total, 162 patients were included (training set: 44, validation set: 118). A model combining cN0 status and T_SUVmax was selected (AUC 0.907, specificity at threshold: 88.2%). In the validation cohort, this model resulted in an AUC of 0.832 and a specificity of 92.3% versus 65.4% for visual interpretation alone (p = 0.02). A total of two false N0 predictions were noted (1 pN1 and 1 pN2). Conclusion: Primary tumor SUVmax improves N status prediction and could allow a better selection of patients who are candidates for minimally invasive approaches.

Blood pool SPECT: rheumatological and orthopedic focus, a pictorial essay.

Single photon emission computed tomography (SPECT) has revolutionized delayed bone scan acquisitions and promises to bring the same benefits to early acquisitions, especially in areas of complex anatomy. To date, however, only a few studies have been published about the utility of blood pool SPECT. The accurate assessment of inflammatory processes can be an indisputable added value to the diagnosis. We present here a series of clinical cases illustrating the utility of blood pool SPECT in various clinical situations in rheumatology and orthopedics. We grouped the cases according to three patterns that facilitate clinical reasoning: inflammatory osseous pathology (pattern A), inflammatory para-osseous pathology (pattern B) and inflammatory extra-osseous pathology (pattern C). A total of seventeen clinical cases are presented. This new semiology requires time and effort to be mastered but expands the diagnostic range offered by bone scintigraphy. More prospective studies on blood pool SPECT will be needed, especially those aiming to clarify its role.

Baseline 18F-FDG Metabolic Tumor Volume Predicts Response to Rituximab Induction in Post-transplant Lymphoproliferative Disorders: A Multi-institutional Retrospective Study.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression. Sequential treatment is commonly proposed, combining induction with rituximab (R-induction) followed by either continuation of treatment or addition of chemotherapy depending on response. Response to R-induction, often assessed by CT scan, is a major predictor of overall survival (OS). The aim of the study was to analyze predictive factors of R-induction response, including total metabolic tumor volume (TMTV), and investigate the role of 18F-FDG PET/CT in response assessment. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. Only patients treated by R-induction with a baseline 18F-FDG PET/CT were included. Response to R-induction was assessed by 18F-FDG PET/CT. The optimal threshold of TMTV for rituximab response was determined using receiver operating characteristic curves. Univariate and multivariate analyses were conducted to identify predictive factors of response. A total of 67 patients were included. Survival characteristics were similar to those previously reported: the complete response rate to R-induction was 30%, the 3-year OS estimate was 66%, and the treatment-related mortality was 4%. The optimal threshold for TMTV to predict R-induction response was 135 cm3. The response rate to R-induction was 38% in the 21 patients with TMTV ≥ 135 cm3 and 72% in the 46 patients with TMTV < 135 cm3. TMTV was a significant predictor of response, both at univariate and multivariate analyses (odd ratios = 3.71, P = 0.022). Baseline TMTV is predictive of response to R-induction. Early assessment of patient response is feasible with 18F-FDG PET/CT.

Bone metastases in midgut neuroendocrine tumors: imaging characteristics, distribution, and risk factors.

PURPOSE: Bone metastases (BM) affect 10-30% of patients with small intestine neuroendocrine tumors (siNET), but little descriptive data are available regarding their distribution throughout the skeleton or potential risk factors. Aim of the study is to better describe the imaging characteristics, distribution, and risk factors of siNET bone metastases using 18F-FDOPA PET/CT. METHODS: All patients with well-differentiated siNET who underwent an 18F-DOPA PET/CT examination in our institution were retrospectively screened between October 2017 and February 2020. Location, SUVmax and CT density of each BM were collected. Sex, metabolic tumor volume (MTV) excluding bone, and metastatic sites other than bone were studied to determine risk factors of BM. RESULTS: Among the 69 patients included, 11 patients (15.9%) presented BM on 18F-FDOPA (65 metastases). The most frequently involved sites were: thoracic spine, pelvic bones and ribs. About 64% of patients presented multiple BM. On coupled CT scan, 63% of BM were not visible. Using an optimal threshold of 19.2 ml, MTV was an independent predictor of BM (p = 0.004) with a derived sensitivity of 100% [65.0-100.0] and a specificity of 70.9% [57.7-81.2]. Hepatic metastatic involvement was also a significant predictor of BM (p = 0.044). CONCLUSION: The development of BM in siNETs appears to be a late event, occurring in patients with a high tumor burden and hepatic involvement. They are often multiple and predominate in the axial skeleton.

Classical Hodgkin Lymphoma: A Joint Clinical and PET Model to Predict Poor Responders at Interim Assessment.

(1) This study aimed to investigate whether baseline clinical and Positron Emission Tomography/Computed Tomography (bPET)-derived parameters could help predicting early response to the first two cycles of chemotherapy (Deauville Score at interim PET, DS at iPET) in patients with classical Hodgkin lymphoma (cHL) to identify poor responders (DS ≥ 4) who could benefit from first-line treatment intensification at an earlier time point. (2) cHL patients with a bPET and an iPET imaging study in our Centre's records (2013−2019), no synchronous/metachronous tumors, no major surgical resection of disease prior to bPET, and treated with two cycles of ABVD chemotherapy before iPET were retrospectively included. Baseline International Prognostic Score for HL (IPS) parameters were collected. Each patient's bPET total metabolic tumor volume (TMTV) and highest tumoral SUVmax were collected. ROC curves and Youden's index were used to derive the optimal thresholds of TMTV and SUVmax with regard to the DS (≥4). Chi-square or Fisher's exact test were used for the univariate analysis. A multivariate analysis was then performed using logistic regression. The type I error rate in the hypothesis testing was set to 5%. (3) A total of 146 patients were included. The optimal threshold to predict a DS ≥ 4 was >177 mL for TMTV and >14.7 for SUVmax (AUC of 0.65 and 0.58, respectively). The univariate analysis showed that only TMTV, SUVmax, advanced disease stage, and age were significantly associated with a DS ≥ 4. A multivariate model was finally derived from TMTV, SUVmax, and age, with an AUC of 0.77. (4) A multivariate model with bPET parameters and age at diagnosis was satisfactorily predictive of poor response at iPET after ABVD induction chemotherapy in cHL patients. More studies are needed to validate these results and further implement DS-predictive factors at baseline in order to prevent poor response and intensify therapeutic strategies a-priori when needed.

18F-Fluoroethylcholine PET/CT Radiomic Analysis for Newly Diagnosed Prostate Cancer Patients: A Monocentric Study.

AIM: The aim of this study is to assess whether there are some correlations between radiomics and baseline clinical-biological data of prostate cancer (PC) patients using Fluorine-18 Fluoroethylcholine (18F-FECh) PET/CT. METHODS: Digital rectal examination results (DRE), Prostate-Specific Antigen (PSA) serum levels, and bioptical-Gleason Score (GS) were retrospectively collected in newly diagnosed PC patients and considered as outcomes of PC. Thereafter, Volumes of interest (VOI) encompassing the prostate of each patient were drawn to extract conventional and radiomic PET features. Radiomic bivariate models were set up using the most statistically relevant features and then trained/tested with a cross-fold validation test. The best bivariate models were expressed by mean and standard deviation to the normal area under the receiver operating characteristic curves (mAUC, sdAUC). RESULTS: Semiquantitative and radiomic analyses were performed on 67 consecutive patients. tSUVmean and tSkewness were significant DRE predictors at univariate analysis (OR 1.52 [1.01; 2.29], p = 0.047; OR 0.21 [0.07; 0.65], p = 0.007, respectively); moreover, tKurtosis was an independent DRE predictor at multivariate analysis (OR 0.64 [0.42; 0.96], p = 0.03) Among the most relevant bivariate models, szm_2.5D.z.entr + cm.clust.tend was a predictor of PSA levels (mAUC 0.83 ± 0.19); stat.kurt + stat.entropy predicted DRE (mAUC 0.79 ± 0.10); cm.info.corr.1 + szm_2.5D.szhge predicted GS (mAUC 0.78 ± 0.16). CONCLUSIONS: tSUVmean, tSkewness, and tKurtosis were predictors of DRE results only, while none of the PET parameters predicted PSA or GS significantly; 18F-FECh PET/CT radiomic models should be tested in larger cohort studies of newly diagnosed PC patients.

Clinical Applications of Immuno-PET in Lymphoma: A Systematic Review.

Objective: Immuno-positron emission tomography (iPET) combines the sensitivity of the PET imaging technique and the targeting specificity of radio-labelled monoclonal antibodies (mAb). Its first clinical applications in humans were described in the late 1990s, and several pathologies have benefitted from this molecular imaging modality since then. Our scope was to assess current clinical applications of immuno-PET in patients with lymphoma. Therefore, a systematic review of the published literature was performed. Methods: PubMed/Medline and Scopus databases were independently searched by two nuclear medicine physicians, to identify studies describing the clinical use of immuno-PET in patients with lymphoma. Methodological quality of the included articles was assessed by using the Quality Assessment of Diagnostic Accuracy Studies criteria. The studies were then analyzed concerning the molecular target of interest. Results: The initial search yielded 1407 articles. After elimination of duplicates, 1339 titles/abstracts were evaluated. Only two articles were found to comply with the inclusion criteria and two more were found during the cross-reference check. Among the four included articles, three described the use of 89Zr-labelled antibodies targeting CD20+ relapsed/refractory B-cell lymphomas and one concerned the use of 68Ga-labelled mAb targeting CXCR4 in patients with non-Hodgkin lymphomas. Conclusions: Very limited literature data are currently available on the clinical use of iPET in patients with lymphoma. This technique is encountering obstacles in its wider use, possibly because of the need of specific facilities, unfavorable dosimetry, and unclear correlation of immuno-tracer biodistribution with patients' clinical and tumors' molecular characteristics. However, iPET may represent a useful tool to non-invasively visualize the heterogenous individual immunological environment, thus potentially guiding treatment-planning in lymphoma patients, and hence deserves further exploitation.

Healthy Organs Uptake on Baseline 18F-FDG PET/CT as an Alternative to Total Metabolic Tumor Volume to Predict Event-Free Survival in Classical Hodgkin's Lymphoma.

Purpose: Healthy organs uptake, including cerebellar and liver SUVs have been reported to be inversely correlated to total metabolic tumor volume (TMTV), a controversial predictor of event-free survival (EFS) in classical Hodgkin's Lymphoma (cHL). The objective of this study was to estimate TMTV by using healthy organs SUV measurements and assess the performance of this new index (UF, Uptake Formula) to predict EFS in cHL. Methods: Patients with cHL were retrospectively included. SUV values and TMTV derived from baseline 18F-FDG PET/CT were harmonized using ComBat algorithm across PET/CT systems. UF was estimated using ANOVA analysis. Optimal thresholds of TMTV and UF were calculated and tested using Cox models. Results: 163 patients were included. Optimal UF model of TMTV included age, lymphoma maximum SUVmax, hepatic SUVmean and cerebellar SUVmax (R2 14.0% - p < 0.001). UF > 236.8 was a significant predictor of EFS (HR: 2.458 [1.201-5.030], p = 0.01) and was not significantly different from TMTV > 271.0 (HR: 2.761 [1.183-5.140], p = 0.001). UF > 236.8 remained significant in a bivariate model including IPS score (p = 0.02) and determined two populations with different EFS (63.7 vs. 84.9%, p = 0.01). Conclusion: The Uptake Formula, a new index including healthy organ SUV values, shows similar performance to TMTV in predicting EFS in Hodgkin's Lymphoma. Validation cohorts will be needed to confirm this new prognostic parameter.

Orbital Metastasis: A Rare but Typical Location of Small Intestine Neuroendocrine Tumor on 18F-FDOPA PET/CT.

ABSTRACT: Orbital foci of increased uptake are sometimes visualized on 18F-FDOPA PET/CT, but the literature remains poor as to their nature. The orbit is indeed a rare site of metastatic involvement. Given this low probability of metastatic location, the question of an incidental benign finding may arise. We reviewed all 18F-FDOPA PET/CT examinations performed at our institution between January 2015 and May 2021: 4/149 patients presented at least 1 orbital focus of increased uptake, all of them presented a metastatic small intestine neuroendocrine tumor. Somatostatin receptor expression was confirmed using 68Ga-DOTATOC PET/CT supporting the hypothesis of genuine metastases.