This clinical review explores adrenal incidentalomas, masses, and pathologies through a comprehensive evaluation of molecular imaging modalities. Molecular imaging is important in the diagnostic and therapeutic management of adrenal gland lesions and masses. Targeted radiopharmaceutical therapies, 131I-MIBG and 177Lu-DOTATATE (Lutathera), and newer theranostic agents can provide personalized treatment plans for patients. This review discusses molecular imaging based on adrenal tumor biology, receptor expression, and genetic mutations, the imaging characteristics of common adrenal lesions, and current and future therapeutic treatments.

Background: Brentuximab vedotin (Bv), Nivolumab (N) and Pembrolizumab (P) have revolutionized the management of advanced stage classical Hodgkin Lymphoma (AS cHL). Significant improvements in both safety and efficacy have been observed with the Echelon-1 (E1) and SWOG S1826 studies. In GHSG HD18 & HD21, PET adapted strategy showed that the numbers of cycles could be reduced without affecting impact on the efficacy. Pembrolizumab followed by AVD in frontline AS cHL with minimal immune mediated adverse events (IMAE) (Allen et al Blood Advances 2023). This study incorporates pembrolizumab into the Bv+AD regimen based on the lower incidence of IMAE observed with pembrolizumab and utilizes a PET-adapted strategy to reduce chemotherapy exposure for participants (pts) with a negative interim PET scan. NCT05922904 Methods: Study enrolled pts with newly diagnosed stage I/II bulky mediastinal disease (≥10 cm), stage III, or stage IV cHL. Pts received 3 cycles of BvP+AD (Bv 1.2 mg/kg capped at 100kg), pembrolizumab 400 mg [P], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D]). Pembrolizumab was administered in Q6 week dosing intervals (C1D1, C2D15, C4D1 and C5D15). Interim PET scan was performed after cycle 3. Subjects achieving PET negativity defined as Deauville scores (DS) of 1 or 2 or 3 with > 90% reduction in total metabolic tumor volume (TMTV) continued in the de-escalation arm. Lesion cut off SUV of 4.0, using MIM software Version 7.4. Subjects on the de-escalation arm completed 3 additional cycles of only BvP. Those pts who received DS of 4, 5 or 3 with less than 90% reduction of TMTV would go on to complete 3 additional cycles of BvP+AD, for a total of 6 BvP+AD. The primary efficacy endpoint is CR rate at the end of therapy (EOT). Key secondary endpoints include safety and tolerability, ORR, duration of response (DOR), duration of complete response (DOCR), and progression-free survival (PFS). Disease response and progression are assessed using Lugano Classification Revised Staging System for malignant lymphoma, incorporating Lymphoma Response to Immunomodulatory Therapy Criteria for nodal non-Hodgkin and Hodgkin lymphomas. Results: Study opened on Jan 2024, planned for 25 pts and the total of 25 were enrolled: median age 31 (19-65), male 52% (13/25), female 48% (12/25), Stage III 20% (5/25) stage IV 44% (11/25) and Stage I/II Bulky 36% (9/25). Caucasian 72% (18/25) Latino 12% (3/25) Asian 12% (3/25). 25 pts completed all six cycles and were evaluable for AE. The most common treatment-related adverse events (AE) of any grade were nausea (20/25, 80%), ALT increase (15/25, 60%), fatigue (15/25, 60%), alopecia (14/25, 56%). 5 SAEs were observed, 3 pts reported fever, 1 pt reported NHL; 1 pt reported diarrhea, however, colonoscopy ruled out colitis; AE of special interest, any grade peripheral sensory neuropathy (20/25, 80%) G1 (16/25, 64%) G2 (4/25, 16%) and no G3. No neutropenic fever was observed. G-CSF was used in 11/25 (44%) pts for primary prophylaxis. No treatment emergent IMAEs were observed, 2 pts developed hypothyroidism. 2 pts discontinued Pembrolizumab, one discontinued due to fever, second due to G3 LFT. 4 pts had dose reduction on Bv due to G2 neuropathy. Twenty five pts completed interim PET scan, 2 pts achieved DS1, 16 pts DS2, and all 7 pts with DS3 achieved >90% TMTV reduction. All 25 pts proceeded to the de-escalation arm to complete 3 additional cycles of BvP only; EOT PET scan reported 5 pts achieved DS1, 15 pts DS2, 2 pts DS3 and 3 pts DS4. At a median follow-up of 11.2 months (6.14 - 19.0 months). The primary endpoint of complete remission at EOT was 88% (22/25), there were no progressions reported. No consolidative radiation therapy was used. Three pts had DS4 at the EOT, one pt had repeat PET follow up demonstrating DS2. Second pt with DS4, at repeat PET continued to have DS4 without increase in size of residual treated mass, which was biopsied demonstrating no evidence of lymphoma. Third pt with DS4 is awaiting biopsy evaluation. Conclusions: PET adapted de-escalation therapy of BvP+AD in AS cHL demonstrated reasonable safety profile and promising efficacy in frontline setting. All pts achieved de-escalation arm, which represented a 50% reduction in anthracycline and alkylating agent exposure, minimizing chemotherapy in young Hodgkin lymphoma population without compromising efficacy. Longer follow up and larger cohort will be needed to provide more robust evidence.

BackgroundStaging patients with high-risk prostate cancer (HRPCa) with conventional imaging of computed tomography (CT) and bone scintigraphy (BS) is suboptimal. Therefore, we aimed to compare the accuracy of whole-body magnetic resonance imaging (WBMRI) with conventional imaging to stage patients with HRPCa. MethodsWe prospectively enrolled patients with newly diagnosed HRPCa (prostate-specific antigen >= 20 ng/ml and/or Grade Group >= 4). Patients underwent BS, CT of the abdomen and pelvis, and WBMRI within 30 days of evaluation. The primary endpoint was the diagnostic performances of detecting metastatic disease to the lymph nodes and bone for WBMRI and conventional imaging. The reference standard was defined by histopathology or by all available clinical information at 6 months of follow-up. To compare diagnostic tests, Exact McNemar's test and area under the curve (AUC) of the receiver operating characteristics curves were utilized. ResultsAmong 92 patients enrolled, 15 (16.3%) and 8 (8.7%) patients were found to have lymphatic and bone metastases, respectively. The sensitivity, specificity, and accuracy of WBMRI in detecting lymphatic metastases were 0.60 (95% confidence interval 0.32-0.84), 0.84 (0.74-0.92), and 0.80 (0.71-0.88), respectively, while CT were 0.20 (0.04-0.48), 0.92 (0.84-0.97), and 0.80 (0.71-0.88). The sensitivity, specificity, and accuracy of WBMRI to detect bone metastases were 0.25 (0.03-0.65), 0.94 (0.87-0.98), and 0.88 (0.80-0.94), respectively, while CT and BS were 0.12 (0-0.53), 0.94 (0.87-0.98), and 0.87 (0.78-0.93). For evaluating lymphatic metastases, WBMRI demonstrated a higher sensitivity (p = 0.031) and discrimination compared to CT (0.72 versus 0.56, p = 0.019). ConclusionsFor staging patients with HRPCa, WBMRI outperforms CT in the detection of lymphatic metastases and performs as well as CT and BS in the detection of bone metastases. Further studies are needed to assess the cost effectiveness of WBMRI and the utility of combined PSMA PET and WBMRI.

Background: Brentuximab vedotin (Bv), Nivolumab (N) and Pembrolizumab (P) have revolutionized the management of advanced stage classical Hodgkin Lymphoma (AS cHL). Significant improvements in both safety and efficacy have been observed with the Echelon-1 (E1) and SWOG S1826 studies. In GHSG HD18 & HD21, PET adapted strategy showed that the numbers of cycles could be reduced without affecting impact on the efficacy. Pembrolizumab followed by AVD in frontline AS cHL with minimal immune mediated adverse events (IMAE)(Allen et al Blood Advances 2023). This study incorporates pembrolizumab into the Bv+AD regimen based on the lower incidence of IMAE observed with pembrolizumab and utilizes a PET-adapted strategy to reduce chemotherapy exposure for patients with a negative interim PET scan. NCT05922904 Objectives: This study aims to assess the safety and efficacy of PET-Adapted de-escalation of chemotherapy regimen after achieving interim PET negative. Methods: Study is enrolling patients with newly diagnosed stage I/II bulky mediastinal disease (≥10 cm), stage III, or stage IV cHL. Subjects will receive three cycles of BvP+AD (Bv 1.2 mg/kg capped at 100kg), pembrolizumab 400 mg [P], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D]). Pembrolizumab was administered in Q6 week dosing intervals (C1D1, C2D15, C4D1 and C5D15), whereas the rest of the regimen were administered Q2 weeks. Interim PET scan was performed after cycle 3. Subjects achieving PET negativity defined as Deauville scores (DS) of 1 or 2 or 3 with > 90% reduction in total metabolic tumor volume (TMTV) will continue in the de-escalation arm. Subjects on the de-escalation arm will complete three additional cycles of only BvP. Subjects with positive interim PET defined as DS of 4, 5 or 3 < 90% reduction of TMTV would proceed with the standard arm to complete three additional cycles of BvP+AD, for a total of six cycles. The primary efficacy endpoint is CR rate at the end of therapy (EOT). Key secondary endpoints include safety and tolerability, ORR, duration of response (DOR), duration of complete response (DOCR), and progression-free survival (PFS). Disease response and progression are assessed using Lugano Classification Revised Staging System for malignant lymphoma, incorporating Lymphoma Response to Immunomodulatory Therapy Criteria for nodal non-Hodgkin and Hodgkin lymphomas. TMTV was calculated using Lesion cut off SUV of 4.0, by MIM software Version 7.4.

Purpose:The primary objective of this study was to evaluate the discriminatory utility of magnetic resonance imaging (MRI), 18F-fluciclovine positron emission tomography (PET), maximum standardized uptake value (SUVmax), prostate-specific antigen (PSA), and combinations of these diagnostic modalities for detecting local prostate cancer recurrence in the setting of rising PSA after radical prostatectomy.Material and methods:Patients were characterised for clinical features such as Gleason score, PSA at surgery, PSA at follow-up, follow-up MRI result, follow-up PET result, follow-up SUVmax, and follow-up disease status. The utility of diagnostic parameters for detecting disease recurrence at the prostatectomy bed was assessed using receiver operating characteristics (ROC) analysis to determine the area under the curve (AUC) for each model. Sensitivity, specificity, and positive/negative predictive values were also calculated. Optimal cut-off points for continuous variables were determined based on maximum Youden's J statistics.Results:The study found that MRI had the highest concordance (96%), sensitivity (100%), specificity (91%), positive predictive value (93%), and negative predictive value (100%) among the diagnostic modalities. The AUC for MRI was 0.9545, indicating a high discriminatory ability for detecting prostate cancer local recurrence. When combined, PET and SUVmax (cut-off value of 2.85) showed an improved performance compared to using them individually, with an AUC of 0.8925.Conclusions:The analysis suggests that MRI is the most effective imaging modality for detecting local prostate cancer recurrence, with 18F-fluciclovine PET and SUVmax also showing promising combined results. PSA has moderate discriminatory utility at follow-up but can still provide valuable information in detecting prostate cancer recurrence. Further research and recent references are needed to support these findings.

The purpose of this study was to evaluate the predictive features of baseline F-18-fluorodeoxy-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT) parameters in patients with dedifferentiated liposarcomas (DDLPSs) and well-differentiated liposarcomas (WDLPSs) receiving systemic treatment. A total of 24 patients with liposarcoma who underwent longitudinal 18F-FDG PET/CT in systemic therapy were included. All volumetric segmentation of each tumor section and semiquantitative imaging parameters were extracted from the axial field of view from both PET and CT images. Maximum, mean, and minimum standardized uptake values (SUVmax, SUVmean, and SUVmin), Hounsfield units (HUs), and their respective changes from baseline and posttreatment were calculated. The voxel values from unenhanced CT images were correlated with PET-derived parameters. The 18F-FDG uptake decreased by more than 56% on average in responders for both SUVmax and SUVmean in DDLPS. There was a decrease in HUmax in DDLPS among responders. Using AUC > 0.8 as a reasonable predictor, we found that the ratios of SUVmaxD/HUmean, SUVmaxD/HUmedian, and SUVmeanD/HUmedian at baseline were significant indicators of the response to treatment in patients with liposarcoma. The changes in SUVmean and not just SUVmax parameters could be considered as accurate tumor response indicators. For the first time, we introduced baseline SUV/HU ratios as a valuable diagnostic tool in predicting liposarcoma treatment outcomes. This ability was not revealed by classic semiquantitative PET or CT parameters at baseline.

Interreader and intrareader reproducibility of 18F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. Methods: 18F-flotufolastat PET/CT images of newly diagnosed (n = 352) or recurrent (n = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. Results: Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. Conclusion: 18F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement.

Supplementary file: Previous therapies, Overall survival S1 : Prior therapies of patients with osteosarcoma enrolled on the Radium 223 trial. Supplementary Table S2: Adverse events in patients with osteosarcoma enrolled on the Radium 223 trial. Supplementary Figure 1: Overall survival of patients with osteosarcoma enrolled on the Radium 223 trial. Supplementary Figure 2: Correlation of % change in RECIST with relative change in LDH. Table 3: Table 1. Ra-223 dichloride Dose Escalation scheme (N=3/cohort)

Prostate cancer (PCa) is one of the most prevalent cancer diagnoses among men in the United States and in several other developed countries. The prostate specific membrane antigen (PSMA) has been recognized as a promising molecular target in PCa, which has led to the development of specific radionuclide-based tracers for imaging and radiopharmaceuticals for PSMA targeted therapy. These compounds range from small molecule ligands to monoclonal antibodies (mAbs). Monoclonal antibodies play a crucial role in targeting cancer cell-specific antigens with a high degree of specificity while minimizing side effects to normal cells. The same mAb can often be labeled in different ways, such as with radionuclides suitable for imaging with Positron Emission Tomography (β+ positrons), Gamma Camera Scintigraphy (γ photons), or radiotherapy (β− electrons, α-emitters, or Auger electrons). Accordingly, the use of radionuclide-based PSMA-targeting compounds in molecular imaging and therapeutic applications has significantly grown in recent years. In this article, we will highlight the latest developments and prospects of radiolabeled mAbs that target PSMA for the detection and treatment of prostate cancer.

Prostate cancer may recur several years after definitive treatment, such as prostatectomy or radiation therapy. A rise in serum prostate-specific antigen (PSA) level is the first sign of disease recurrence, and this is termed biochemical recurrence. Patients with biochemical recurrence have worse survival outcomes. Radiologic localization of recurrent disease helps in directing patient management, which may vary from active surveillance to salvage radiation therapy, androgen-deprivation therapy, or other forms of systemic and local therapy. The likelihood of detecting the site of recurrence increases with higher serum PSA level. MRI provides optimal diagnostic performance for evaluation of the prostatectomy bed. Prostate-specific membrane antigen (PSMA) PET radiotracers currently approved by the U.S. Food and Drug Administration demonstrate physiologic urinary excretion, which can obscure recurrence at the vesicourethral junction. However, MRI and PSMA PET/CT have comparable diagnostic performance for evaluation of local recurrence after external-beam radiation therapy or brachytherapy. PSMA PET/CT outperforms MRI in identifying recurrence involving the lymph nodes and bones. Caveats for use of both PSMA PET/CT and MRI do exist and may cause false-positive or false-negative results. Hence, these techniques have complementary roles and should be interpreted in conjunction with each other, taking the patient history and results of any additional prior imaging studies into account. Novel PSMA agents at various stages of investigation are being developed, and preliminary data show promising results; these agents may revolutionize the landscape of prostate cancer recurrence imaging in the future. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. See the invited commentary by Turkbey in this issue. The slide presentation from the RSNA Annual Meeting is available for this article.

P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were defined on aligned reference CT and serial SPECT images. Organs with the highest estimated dose values (mSv/MBq) for FF-21101(111In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101(90Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101(111In) exhibits favorable biodistribution in cynomolgus macaques and estimated human dosimetric characteristics. Data obtained in this study were used to support the filing of an investigational new drug application with the FDA for a Phase I clinical trial.

Prostate-specific membrane antigen (PSMA) is a transmembrane type II glycoprotein with the catalytic site positioned in the extracellular domain of the molecule. Following its discovery in 1987, it was cloned and subsequently identified in human tissues. While PSMA is expressed in normal prostatic parenchyma, expression levels are higher in benign epithelium and even higher in adenocarcinoma. Initially, anti-PSMA monoclonal antibodies were instrumental in establishing that overexpression of PSMA was not confined to prostate tissue or prostate cancer. Rather, a number of studies reported its expression in a number of non-prostatic tumors, including breast, lung, renal, colon, urinary bladder, nervous systems, gastric and other malignancies. The differential in expression levels plus accessibility to the catalytic site via a parenteral route of administration have led to the development of a number of small and highly specific PSMA-targeting radiopharmaceuticals. Because of the many advantages of radiochemical synthesis with positron-emitting radionuclides and imaging capabilities of Positron Emission Tomography (PET), the two technologies have been used to evaluate a number of promising 18F- and 68Ga-based molecular imaging agents. While there are a number of small PSMA-targeting molecules under development, the three that have advanced the most in the clinic are: 68Ga-PSMA-11, 18F-DCFPyL and 18F-PSMA-1007. The FDA recently granted NDAs to UCLA and UCSF for 68Ga-PSMA-11 production, and Lantheus Holdings, Inc. for 18F-DCFPyL for PET imaging of men with prostate cancer. Other groups are developing radiopharmaceuticals conjugated with both imaging (18F) and therapeutic radionuclides (177Lu, 188Re, 225Ac) for use in theranostic settings. Finally, efforts are underway to provide greater access, cost efficiency and productivity to these PSMA-PET technologies by automating the production process. The convergence of our increasing understanding of PSMA biology and the technological advancements to allow more widespread use of PSMA-PET will ultimately have positive benefits for treatment management of cancer patients.

Table 1: Patient characteristics and PET-derived parameters Background: Advanced-stage classical Hodgkin’s lymphoma (cHL) is a curable malignancy, however up to 25% of patients may relapse following frontline multiagent-chemotherapy. Novel treatment options such as PD-1 inhibitors and antibody-drug conjugates (ADC) have demonstrated high efficacy with favorable safety profiles in frontline and relapsed cHL. Early reduction in volumetric and metabolic PET parameters have been reported as effective predictors of outcome in cHL. Here, we describe the changes in metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) after two cycles of therapies containing nivolumab, brentuximab vedotin (Bv), or both in advanced cHL. Methods: We retrospectively enrolled subjects with newly diagnosed, advanced stage cHL who received therapy in three protocols: Bv-nivolumab-AD, Bv-AVD, or nivolumab-AVD. All protocols did not allow for radiation consolidation. Baseline (PET0) and interim PET after two cycles (PET2) were analyzed and cHL lesions were segmented using a threshold of 41% of the SUVmax. MTV, TLG, and SUVmax were recorded at both time-points and percentage changes were calculated as ΔMTV, ΔTLG, and ΔSUVmax, respectively. Summary statistics were reported, and Kurskal-Wallis test was used to compare PET-parameters among the groups with P<0.05 considered statistically significant. Results: A total of 27 subjects were included in the final analysis. Subjects were treated with Bv-nivolumab-AD (n=16), Bv-AVD (n=5) and nivolumab-AVD (n=6). The distribution of MTV, TLG, and SUVmax values at PET0 and PET2 were not significantly different across the three groups. The median (IQR) ΔMTV of all study subjects was 100% (99.2%–100%), ΔTLG 100% (99.69%–100%) and ΔSUVmax 100% (68.1%–100%). Initial observation suggested that subjects receiving nivolumab-AVD had less tumor burden reduction rate compared to Bv-nivolumab-AD and Bv-AVD groups. However, this difference was not statistically significant (P=0.10) (Table 1) Conclusion: This is the first report to describe PET-derived metabolic changes in advanced stage cHL patients receiving nivolumab and/or Bv-based regimens. Our initial results suggest a significant and comparable reduction in MTV, TLG, and SUVmax among the three treatment groups. The limited sample size did not confirm an initial observation of higher reductions in patients receiving Bv-based strategies. Future studies are needed to further explore and validate these findings.

Background: Elderly patients (pts) diagnosed with classical Hodgkin lymphoma have poorer outcomes relative to younger counterparts. Elderly pts have comorbidities which contributes to treatment delays and higher rates of toxicities, leading to poor clinical outcome. Frailty measurements are subjective and cumbersome to perform in busy clinical settings. Body composition analysis based on CT has shown prognostic value in several malignancies in this age group. We therefore report the findings of body composition analysis in elderly cHL pts in the frontline setting. Methods: Pts aged ≥60 with newly diagnosed cHL treated with combinations of anti-PD1 antibody nivolumab (Nivo), brentuximab vedotin (Bv), and/or chemotherapy between 2014 and 2021 were queried. We excluded pts with concomitant malignancies or unavailable baseline imaging. Patient characteristics were scored. Baseline axial CT images at the level of 3rd lumbar vertebra (L3) were segmented using MIM 7.2 (MIM Software Inc, Cleveland, OH). Cross sectional areas of skeletal muscle (SKM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were measured based on densities of −29 to +150, −190 to −30, and -150 to -50 hounds field units (HUs), respectively. Total adipose tissue (TAT) was obtained as sum of VAT and SAT. An index of each was calculated by normalization for stature (height in m2). Radiation attenuation of skeletal muscles density (SMD) was measured as mean HUs at the same level. The primary end point was progression free survival (PFS). Receiver operating characteristics (ROC) curves were used to determine optimal cutoff points. Kaplan-Meier analyses were used to compare survival. P<0.05 was considered statistically significant. EOT response assessment was done according to Lugano 2014 criteria. Results: A total of 63 newly diagnosed elderly cHL patients were screened and 33 patients met the eligibility criteria, males were 20 (61.5%), median age 73.8, range (71.2, 77.2), advanced stage 24 (72%). Fifteen (45.4%) were treated with AVD/ABVD, 12 (36.4%) Bv-AVD/AD and 6 (18.2) Nivo Bv. Response at interim PET (iPET) was negative in 26 (78.8%). Complete remission at EOT was observed in 28 (84.8%) patients. Among body composition variables, SMD showed consistent correlation with survival in both males and females (AUC=0.76 and 0.76, respectively). Cutoffs of 40 HU in males and 28 HU in females were used to group the patients into high- and low-SMD. The SMD was not significantly different between treatment groups (P=0.64) and distribution of age and BMI were the same in low and high SMD (P= 0.84, and 0.81, respectively). Patients with low SMD had a CR rate of 69.2% compared to 95% in the high SMD patients (P<0.05), while patients with negative iPET achieved 91% CR at EOT compared to 71.4% in positive iPET (P=0.20). The mean follow-up time of the study cohort was 55.7 months (CI 95% 46.2, 65.4). High SMD group had a 48-months PFS of 89% vs 58% in pts with low SMD (P=0.013). Combining SMD and iPET status allowed for enhanced stratification of the iPET-negative group: pts with high SMD and iPET negative iPET had 93% PFS compared to 62.5% PFS in low SMD and iPET negative iPET at 48 months (P<0.01) (Figure-1) Conclusion: Our results suggest that SMD may add value to the prognostication in elderly pts with cHL. In addition, the incorporation of SMD with iPET could identify a cluster of pts with low SMD who had worse prognosis compared to those with high SMD. This may allow for better treatment adjustments in this population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ABSTRACT:Antibody-drug conjugates (ADCs) are designed to deliver cytotoxic payloads to distinctive target-expressing cancer cells. Following internalization, the ADCs are routed to different compartments in the cells, where cleavage of the linker causes release of the cytotoxic cargo. With such a delivery system, more effective payloads can reach cancer cells, allowing for more efficient treatment and dosing schedule. The monoclonal antibody (mAb) component of ADC plays a crucial role in the effective targeting of cancer cell-specific antigens while minimizing binding to normal cells. Often, the same mAbs used in ADCs can be labeled instead with radionuclides suitable for positron emission tomography or gamma-camera scintigraphy. To achieve high sensitivity and specificity for imaging, radiolabeled mAbs must have high affinity for the antigen, favorable pharmacokinetic properties, and a low toxicity profile. The use of radiolabeled mAbs permits the noninvasive interrogation of specific target expression on tumor cells and assessment of tumor heterogeneity in vivo by a simple diagnostic imaging scan that may include the whole body in the field of view. With this approach, radiolabeled mAbs can serve as important imaging biomarkers to predict the optimal delivery of ADCs to tumors and be used to monitor therapy with follow-up scans. Moreover, the same mAb can then be radiolabeled with an analogous radionuclide for the delivery of β-emitters, α-particles, or Auger electrons as part of a radioimmunotherapy approach. The purpose of this review is to introduce key concepts regarding radiolabeled mAbs targeting various tumor antigens (CD20, CDH3, type I insulinlike growth factor receptor, prostate-specific membrane antigen, and human epidermal growth factor receptor 2) that are being used in the clinical setting or undergoing development.