EJNMMI Research最新文献

Background: [^99mTc]Tc-MIBI is a conventional myocardial perfusion radiotracer, and is predominantly taken up by mitochondria in a manner dependent on mitochondrial membrane potential. This study aimed to repurpose [^99mTc]Tc-MIBI for functional renal imaging to evaluate mitochondrial dysfunction in chronic kidney disease (CKD).

Results: A total of 11 patients with newly diagnosed CKD and 27 matched healthy volunteers underwent [99mTc]Tc-MIBI dynamic renal scans and SPECT/CT. Quantitative analyses of the left kidneys assessed time-activity curves, percentage of renal uptake, and standardized uptake values (SUV). Renal mitochondrial content in CKD patients was evaluated using immunohistochemistry of kidney biopsy samples. CKD patients had comparable eGFR to healthy volunteers but exhibited significantly lower renal [^99mTc]Tc-MIBI uptake percentage on dynamic scan and decreased SUV on SPECT/CT. A positive correlation was observed between mean SUV and renal mitochondrial content in CKD patients. Mean SUV was identified as an independent predictor of CKD (odds ratio 0.2, P = 0.037), demonstrating high diagnostic accuracy (AUC = 0.886), whereas conventional biomarkers had limited predictive value.

Conclusions: [^99mTc]Tc-MIBI kidney SPECT/CT effectively detected renal mitochondrial dysfunction in patients with CKD, suggests its potential as a noninvasive imaging biomarker. SUV may serve as a quantitative parameter for assessing renal mitochondrial dysfunction.

Background: One of the most studied, and preclinically as well as clinically applied gastrin-releasing peptide receptor (GRPR) ligands represents the antagonist RM2 (DOTA-Pip⁵-D-Phe⁶-Gln⁷-Trp⁸-Ala⁹-Val¹⁰-Gly¹¹-His¹²-Sta¹³-Leu¹⁴-NH₂). As an improved in vivo stability was observed for a RM2 analog comprising the unnatural amino acid α-methyl-L-tryptophan instead of L-Trp, we aimed to elucidate the impact of other unnatural amino acids (homoserine [Hse], β-(3-benzothienyl)alanine [Bta]) at the metabolically less stable Gln-Trp site. Furthermore, we conjugated either DOTA, NOTA or NODAGA to the RM2 peptide and its modified derivatives, and evaluated each analog preclinically using ⁶⁸Ga and ⁶⁴Cu, as well as ¹⁷⁷Lu (only DOTA-comprising compounds).

Results: GRPR affinity and lipophilicity of RM2 derivatives were in a range of 1.2-8.4 nM and - 2.9 to - 1.1 (^nat/68Ga-labeled), 1.7-33.0 nM and - 2.4 to - 1.6 (^nat/64Cu-labeled), as well as 3.0-19.7 nM and - 3.2 to - 1.8 (^nat/177Lu-labeled), respectively. Both, [¹⁷⁷Lu]Lu-[Hse⁷]RM2 and [¹⁷⁷Lu]Lu-[Bta⁸]RM2 revealed distinctly lower in vivo stability (< 20% intact at 15 min post-injection) than [¹⁷⁷Lu]Lu-[α-Me-Trp⁸]RM2 (= [¹⁷⁷Lu]Lu-AMTG) and [¹⁷⁷Lu]Lu-RM2 (> 30% intact at 30 min post-injection). Both [⁶⁸Ga]Ga-RM2 and [⁶⁸Ga]Ga-AMTG exhibited high tumor (~ 15 percentage injected dose per gram, %ID/g) and pancreas uptake (> 25%ID/g), whereas [⁶⁸Ga]Ga-[Hse⁷]RM2 and [⁶⁸Ga]Ga-[Bta⁸]RM2 revealed lower tumor (~ 7.5%ID/g) but also substantially lower pancreas uptake (< 8%ID/g) at 1 h post-injection. At 24 h post-injection (p.i.), [¹⁷⁷Lu]Lu-RM2 and [¹⁷⁷Lu]Lu-AMTG exhibited high (> 8% ID/g) while [¹⁷⁷Lu]Lu-[Hse⁷]RM2 and [¹⁷⁷Lu]Lu-[Bta⁸]RM2 displayed low tumor retention (~ 2%ID/g). All compounds showed low activity levels in the pancreas at 24 h post-injection (< 1%ID/g).

Conclusion: Substitution of the Gln-Trp site in RM2 by artificial amino acids had a distinct impact on overall pharmacokinetics. While Hse (instead of Gln) and Bta (instead of Trp) led to a decreased, α-Me-Trp (instead of Trp) led to an increased in vivo stability, which resulted in improved pharmacokinetics over time in case of the latter. However, at 1 h post-injection both [⁶⁸Ga]Ga-[Hse⁷]RM2 and [⁶⁸Ga]Ga-[Bta⁸]RM2 displayed slightly higher tumor-to-pancreas and tumor-to-intestine ratios, rendering homoserine and β-(3-benzothienyl)alanine potential options for the modification of GRPR ligands with regard to imaging properties.

Background: Surgical resection offers long-term survival for liver malignancies, but insufficient future liver remnant (FLR) volume often precludes operability. This study evaluated yttrium-90 selective internal radiation therapy (⁹⁰Y-SIRT) for controlling right-liver tumors and inducing compensatory left-lobe hyperplasia.

Results: Thirty-seven patients (29 hepatocellular carcinomas, 2 intrahepatic cholangiocarcinoma, 6 liver metastasis of colorectal cancer) with right-liver tumors underwent ⁹⁰Y-SIRT. Tumor volume decreased significantly by 133 mL at 1 month and 206 mL at 3 months post-treatment (both P < 0.001). Right-liver volume reduction averaged 182 mL at 1 month (P < 0.001) and 300 mL at 3 months (P < 0.001). Concurrently, left-liver volume increased by 55 mL (P < 0.001) and 127 mL (P < 0.001) at 1 and 3 months, respectively, while FLR percentage rose by 5.8% (P < 0.001) and 11.9% (P < 0.001). Per mRECIST criteria, 3-month imaging revealed an objective response rate (ORR) of 78.4% and disease control rate (DCR) of 91.9%. In 14 patients downstaged to resection/transplantation, ICG-R15 levels remained stable, confirming preserved liver reserve function post-90Y-SIRT. These findings demonstrate ⁹⁰Y-SIRT effectively controls right-lobe tumor progression and stimulates compensatory left-lobe hypertrophy, enabling FLR expansion. The treatment achieved high ORR, significant tumor downstaging, and pathological necrosis without compromising hepatic functional reserve.

Conclusions: 90Y-SIRT represents a safe and efficacious strategy to convert initially unresectable patients into surgical candidates.

Background: Body composition (BC) analysis is performed to quantify the relative amounts of different body tissues as a measure of physical fitness and tumor cachexia. We hypothesized that relative changes in body composition (BC) parameters, assessed by an artificial intelligence-based, PACS-integrated software, between baseline imaging before the start of radioligand therapy (RLT) and interim staging after two RLT cycles could predict overall survival (OS) in patients with metastatic castration-resistant prostate cancer.

Methods: We conducted a single-center, retrospective analysis of 92 patients with mCRPC undergoing [¹⁷⁷Lu]Lu-PSMA RLT between September 2015 and December 2023. All patients had [⁶⁸ Ga]Ga-PSMA-11 PET/CT at baseline (≤ 6 weeks before the first RLT cycle) and at interim staging (6-8 weeks after the second RLT cycle) allowing for longitudinal BC assessment.

Results: During follow-up, 78 patients (85%) died. Median OS was 16.3 months. Median follow-up time in survivors was 25.6 months. The 1 year mortality rate was 32.6% (95%CI 23.0-42.2%) and the 5 year mortality rate was 92.9% (95%CI 85.8-100.0%). In multivariable regression, relative change in visceral adipose tissue (VAT) (HR: 0.26; p = 0.006), previous chemotherapy of any type (HR: 2.4; p = 0.003), the presence of liver metastases (HR: 2.4; p = 0.018) and a higher baseline De Ritis ratio (HR: 1.4; p < 0.001) remained independent predictors of OS. Patients with a higher decrease in VAT (< -20%) had a median OS of 10.2 months versus 18.5 months in patients with a lower VAT decrease or VAT increase (≥ -20%) (log-rank test: p = 0.008). In a separate Cox model, the change in VAT predicted OS (p = 0.005) independent of the best PSA response after 1-2 RLT cycles (p = 0.09), and there was no interaction between the two (p = 0.09).

Conclusions: PACS-Integrated, AI-based BC monitoring detects relative changes in the VAT, Which was an independent predictor of shorter OS in our population of patients undergoing RLT.

Background: For patients diagnosed with primary aldosteronism (PA) accompanied by bilateral adrenal lesions, identifying optimal candidates for surgical intervention remains a significant clinical challenge. Although adrenal venous sampling (AVS) is currently the gold standard for lateralizing aldosterone hypersecretion, its technical complexity, invasiveness, and interpretive difficulties restrict its widespread adoption. In this study, we aimed to investigate the clinical application of ⁶⁸Ga-pentixafor positron emission tomography/computed tomography (PET/CT) as a non-invasive imaging modality in AVS-free surgical decision-making for PA patients with bilateral adrenal lesions.

Results: Among the 51 patients who underwent ⁶⁸Ga-pentixafor PET/CT, 36 patients had adrenalectomy, with the surgical side determined by PET/CT lateralization. The postoperative complete biochemical and clinical success rates for these patients were 91.67% and 100%, respectively. Additionally, receiver operating characteristic curve analysis indicated that PET/CT results were favorable predictors of postoperative outcomes in surgical patients. Postoperative pathological evaluation of ⁶⁸Ga-pentixafor PET/CT-guided surgical patients revealed that 86.11% had adrenocortical adenomas with positive CYP11B2 and CXCR4 expression.

Conclusion: CXCR4-targeted ⁶⁸Ga-pentixafor PET/CT can be effectively utilized in surgery decision-making for PA patients with bilateral adrenal lesions, offering a potential alternative to AVS and maybe applied to predict postoperative biochemical and clinical success.

Trial registration: ⁶⁸Ga-Pentixafor PET/CT for Guiding Surgical Treatment of Primary Aldosteronism With Bilateral Adrenal Lesions; Trial registration number: NCT06247566; Date of registration: 2021-11-01; URL of trial registry record: https://clinicaltrials.gov/study/NCT06247566 .