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Simple Summary: Despite novel targeted treatment options, small cell lung cancer (SCLC) still has a bad prognosis. However, as a relevant number of SCLC patients show a high expression of somatostatin receptors (SSTRs), SSTR-targeted radionuclide therapy (PRRT) may be a treatment option. Therefore, we investigated whether SSTR expression assessed in positron emission tomography (PET) has prognostic value. In patients with adequate PET uptake, PRRT was performed, and the outcome was investigated. We found that SSTR-targeted PET, although not a prognostic tool for outcome, is an important tool for treatment decision. In some patients, PRRT can be a promising treatment option as a second or third line treatment of SCLC. Background: Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). Methods: A total of 67 patients (26 females; age, 41–80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. Results: On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, ρ = 0.13 with p = 0.30 and vs. OS, ρ = 0.00 with p = 0.97; T/L vs. PFS, ρ = 0.07 with p = 0.58 and vs. OS, ρ = −0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. Conclusions: SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Discordant FDG-positive but PSMA-negative (FDG+/PSMA−) metastases constitute a negative prognostic marker of overall survival in patients undergoing PSMA radioligand therapy (RLT). The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions, which occur during or after PSMA RLT. In a retrospective bicentric analysis of 32 patients undergoing PSMA RLT and follow-up dual tracer staging with PSMA and FDG PET/CT, FDG+/PSMA− lesions occurred in a limited number of patients. However, the presence of FDG+/PSMA− lesions appears not to have a significant impact on the OS, but further studies are needed to establish the clinical relevance of such lesions. Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [18F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions. [ABSTRACT FROM AUTHOR]

11 C-methionine ( 11 C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18 F-fluorodeoxyglucose ( 18 F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11 C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18 F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11 C-MET and 18 F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11 C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11 C-MET detected more focal lesions (FL) than FDG ( p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11 C-MET than in 18 F-FDG ( p < 0.05, respectively). 11 C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11 C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18 F-FDG. Its implications for prognosis evaluation need further investigation.

The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [ 68 Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [ 68 Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68 Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68 Ga. The significantly increased foci numbers after [ 68 Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity., Competing Interests: The authors declare no conflict of interest.