Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.

Peptide receptor radionuclide therapy (PRRT) has been used for more than twenty years as a systemic treatment approach in inoperable or metastatic somatostatin receptor (SSTR)-positive tumors. The purpose of this study was to analyze the long-term outcome of PRRT with regard to the most commonly used radiopharmaceuticals, ⁹⁰Y-DOTA-Tyr3-octreotide (⁹⁰Y-DOTA-TOC) and ¹⁷⁷Lu-DOTA-Tyr3-octreotate (¹⁷⁷Lu-DOTA-TATE). Methods: This retrospective clinical study included a total of 44 consecutive patients (27 men) with advanced tumors and enhanced SSTR expression. Mean age at initial diagnosis was 60 years (SD 11.3, range 40 to 84 years). Median follow-up was 80 months. In the mean 5.3 ± 2.5 cycles were administered for ¹⁷⁷Lu-PRRT with mean activity of 27.2 ± 14.9 GBq per patient and 5.5 ± 2.6 cycles for ⁹⁰Y-PRRT with mean activity of 14.7 ± 7.3 GBq. Overall, 378 cycles were administered (mean 8.6 ± 3.4 cycles per patient) with an overall cumulative activity of 1514.1 GBq. Results: Median overall survival (OS) was 79 months. Twenty-one (77.8%) of the 27 men and nine (52.9%) of the 17 women had died 12 years after commencement of PRRT. Shortest duration of illness was eight months, longest 155 months. Severe side-effects (WHO Grades III and IV) are seen in nine of the 14 patients still alive. Chronic kidney disease in combination with anemia is the most common finding in the nine patients with severe side-effects. Very poor prognosis was found for those patients who showed progressive disease (PD) in comparison with patients with cumulative disease control after initial PRRT (log-rank, p<0.001), while women and patients with no more than two tumor sites seem to especially benefit from PRRT not reaching significance levels. Conclusion: PRRT is very encouraging in terms of long-term outcome. Thirty-two percent (14/44 patients) of the patients with metastatic or inoperable disease are still alive more than 12 years after the beginning of radionuclide therapy. Possible predictors for favourable outcome are initial response to PRRT, number of affected sites and female gender.

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such, data for first-line ICI therapy and especially for chemotherapy–ICI combinations are still scarce, we retrospectively evaluated baseline ¹⁸F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n = 70) or as monotherapy (n = 15). Maximum and mean standardized uptake value, total metabolic tumor volume (MTV), total lesion glycolysis, bone marrow-/and spleen to liver ratio (BLR/SLR) were calculated. Kaplan–Meier analyses and Cox regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Median follow-up was 12 months (M; 95% confidence interval 10–14). Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p < 0.001). Median PFS/OS were significantly longer in patients with MTV ≤ 70 mL vs. >70 mL (PFS: 10 M (4–16) vs. 4 M (3–5), p = 0.001; OS: not reached vs. 10 M (5–15), p = 0.004). Disease control rate was 81% vs. 53% for MTV ≤/> 70 mL (p = 0.007). BLR ≤ 1.06 vs. >1.06 was associated with better outcomes (PFS: 8 M (4–13) vs. 4 M (3–6), p = 0.034; OS: 19 M (12-/) vs. 6 M (4–12), p = 0.005). In patients with MTV > 70 mL, concomitant BLR ≤ 1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI-treated NSCLC, with BLR allowing additional risk stratification.

Objective: ¹⁸F-FDG PET/CT provides information on disease extension and activity in neoplastic and inflammatory conditions. So far, little is known about whether SUVmax of a reference lesion can allow a prognosis to be given regarding patient-specific outcome parameters in complex cases of tuberculosis (TB). Methods: We retrospectively identified 37 patients (21 men, 16 women; mean age, 50.4 years) who underwent ¹⁸F-FDG PET/CT for the evaluation of active TB before treatment initiation. The aims were to examine whether the reference lesion SUVmax differed between patients with standard (≤9 months) and long-term (>9 months) therapy and to define an SUVmax cutoff distinguishing those groups. In addition, we analyzed the prognostic value of SUVmax with regard to estimation of initial disease extent and lesion distribution pattern. Results: Median therapy duration was 10 months (interquartile range, 3.25 months), and median SUVmax was 8 (interquartile range, 8.54). SUVmax was significantly (P = 0.036) higher in patients treated longer than 9 months (10.1 vs 5.5). When applying a receiver operating characteristic curve analysis, an SUVmax cutoff value of 10 differentiated the standard and the long-term therapy group with a sensitivity of 50% and a specificity of 78.6% (P = 0.087). Higher SUVmax corresponded with a larger number of affected organ systems (P = 0.012 for ≤/>1). Patients with extrathoracic involvement showed significantly higher SUVmax than did patients with limited intrathoracic disease (P = 0.024) and received significantly longer antimycobacterial therapy (P = 0.011). Conclusions: Reference lesion SUVmax from pretherapy ¹⁸F-FDG PET/CT may have prognostic properties in complicated cases of TB, especially regarding therapy duration and disease extent.

Purpose: The aim of this study was to evaluate the diagnostic performance of ¹⁸F-choline PET and MRI in patients with primary hyperparathyroidism. Furthermore, the additional value of software-based PET/MRI scan fusion was analyzed. Patients and Methods: This retrospective study includes 42 patients (38 women) with an age between 32.5 and 79.1 years. PET/CT scans were performed on a dedicated system after injection of 250 to 350 MBq ¹⁸F-choline. For the MRI examination, T1-weighted images of the cervical region were used. The image fusion was made by anatomical coregistration using an automated algorithm based on mutual information. Results: A total of 46 lesions were discovered and histologically confirmed in 42 patients. Histopathological examination revealed 38 adenomas and 8 hyperplasias. This means that, in 4 of these 42 patients, 2 lesions per patient were discovered. PET/CT also detected 46 abnormal findings, but only 43 were correctly recognized, whereas the other 3 were false-positive (FP). Six lesions could not be detected correctly: 3 were FP and 3 false-negative, which resulted in a sensitivity of 93.5% and a specificity of 97.5%. The site-specific evaluation showed 18 true-positive enlarged parathyroid glands with MRI, but also produced 13 FP findings and failed to detect 28 lesions; the sensitivity and specificity are thus 39.1% and 89.3%, respectively. The difference in detection rate between ¹⁸F-choline PET/CT and MRI was statistically significant (P < 0.001). Conclusions: ¹⁸F-choline PET/CT is clearly superior to MRI for localization diagnostics in primary hyperparathyroidism. Image fusion of both modalities can be helpful for more precise anatomical assignment.