Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

Microtubules are cytoskeletal components that play essential roles in the brain, including supporting neuronal structure, protein transport, and cognitive function. In vivo quantification of microtubule dynamics using PET is possible with ¹¹C-MPC6827, a brain-penetrant radiotracer that has been evaluated in mice and nonhuman primates. Here we present the first assessment of ¹¹C-MPC6827 test-retest properties in a healthy human brain and examine the influence of scan duration on repeatability. Methods: Five healthy volunteers underwent two 90-min ¹¹C-MPC6827 PET scans with concurrent arterial blood sampling (4 imaged twice in 1 d, 1 rescanned after 1 y). Radiotracer time-activity curves were extracted from 46 individual brain regions, in addition to the whole brain. Total distribution volume (V _T) was estimated using kinetic models and graphical analysis. SUVs and the SUV ratio to whole brain (SUVR_WB) were computed in 2 postinjection time windows. Repeatability was assessed using absolute test-retest percent difference (TRPD) and intraclass correlation coefficient (ICC). Time stability was examined by truncating imaging data from 90-min to 60-min acquisition and comparing computed outcomes to the 90-min value as gold standard. Results: V _T estimates were stable with truncated scan time (average shorter V _T/90-min V _T, 1.003-1.030). For the same-day test-retest pairs, V _T estimates obtained with kinetic models showed average TRPD values, across regions and participants, between 10.18% and 14.26%, and ICCs between 0.483 and 0.966. Graphical approaches demonstrated lower repeatability than kinetic models. Across methods, TRPDs were lower and ICCs were higher with shorter scans. SUV showed higher interscan variability in TRPD. SUVR_WB was more stable (TRPD, 2.22%-5.47%) and less influenced by scan duration. However, ICCs were overall much lower for SUV and SUVR_WB than for V _T Conclusion: ¹¹C-MPC6827 shows good repeatability for quantifying microtubule dynamics in humans using arterial blood even at a 60-min scan duration. SUVR_WB could be a convenient blood-free alternative to V _T.

Peptide receptor radionuclide therapy (PRRT) using α-particle emitters has potential to provide improved patient outcomes over those achieved with β-particle PRRT. A promising candidate radiopharmaceutical pair, PSC-PEG₂-TOC (VMT-α-NET) conjugated to ²⁰³Pb for SPECT/CT imaging or ²¹²Pb for α-PRRT, is currently in early-phase clinical trials for patients with neuroendocrine tumors (NETs). Here, we present the imaging and dosimetry characteristics of this theranostic approach. Methods: A phase 0 imaging trial of [²⁰³Pb]Pb-VMT-α-NET was conducted between January and December of 2023. Ten participants with somatostatin receptor type 2 (SSTR2)-positive NETs underwent SPECT/CT and blood sampling at 1, 4, 24, and 48 h after intravenous infusion of approximately 185 MBq of [²⁰³Pb]Pb-VMT-α-NET. The diagnostic performance of [²⁰³Pb]Pb-VMT-α-NET was evaluated through lesion-by-lesion comparison against baseline SSTR2 PET/CT. A subset of lesions was further analyzed for signal-to-noise ratio to determine the optimal diagnostic imaging time point after [²⁰³Pb]Pb-VMT-α-NET administration. Patient-specific dosimetry of [²¹²Pb]Pb-VMT-α-NET was derived from ²⁰³Pb imaging and performed assuming local α- and β-particle energy deposition in tumors and normal organs. Effects of daughter ion relocation were considered using a whole-body pharmacokinetic model on the basis of parameters published by the International Commission on Radiological Protection. Results: Of the 162 total lesions identified on SSTR2 PET/CT scans, only 97 were detected on [²⁰³Pb]Pb-VMT-α-NET SPECT/CT. The highest signal-to-noise ratio for lesions occurred 4 h after [²⁰³Pb]Pb-VMT-α-NET administration. Sensitivity was 94% for lesions larger than 1 cm versus 35% for lesions no larger than 1 cm or nonmeasurable lesions. The effective dose associated with [²⁰³Pb]Pb-VMT-α-NET administration was 0.038 mSv/MBq (1.40 mSv/mCi). Estimated dosimetry for [²¹²Pb]Pb-VMT-α-NET (mean ± SD, not adjusted for relative biologic effectiveness) based on [²⁰³Pb]Pb-VMT-α-NET SPECT/CT was 15 ± 4.7 mGy/MBq for the kidneys, 8.4 ± 4.1 mGy/MBq for the spleen, 2.5 ± 0.8 mGy/MBq for the liver, 0.324 ± 0.108 mGy/MBq for the blood, 0.270 ± 0.081 mGy/MBq for the whole body, and 29.6 ± 25.8 mGy/MBq for tumors. Renal absorbed dose projections for ²¹²Pb were estimated to carry an overall standard uncertainty (k = 1) of 15.3%. Conclusion: [²⁰³Pb]Pb-VMT-α-NET appears to be a safe and effective SPECT/CT tracer for imaging NETs larger than 1 cm and for normal organ and tumor radiation dosimetry. The chemically matched ²⁰³/²¹²Pb theranostic pair offers the potential for a dosimetry-driven personalized treatment paradigm.

Staging of prostate carcinoma (PCa) still largely relies on histopathologic examination of prostate tissue. In the last few years, PET/CT with radiotracers that target the prostate-specific membrane antigen (PSMA) has emerged as a noninvasive and sensitive method for staging of PCa. Compared with [⁶⁸Ga]PSMA-11, [¹⁸F]PSMA-1007 is a relatively new radiotracer for PSMA PET/CT with favorable characteristics such as a longer physical half-life, reduced bladder background uptake, and improved availability due to production off-site. The objective of this systematic review and metaanalysis is to summarize the efficacy of [¹⁸F]PSMA-1007 in primary T, N, and M staging of PCa in comparison to histopathology. Methods: Clinical trials on primary staging of PCa with [¹⁸F]PSMA-1007 (both prospective and retrospective studies) were identified by a systematic search in PubMed. Relevant literature used histopathology as a comparator and reported discrete values for sensitivity and specificity. A metaanalysis assessed differences in diagnostic parameters. Results: Nineteen studies were included in this review: 10 studies reported on T staging (739 patients), 8 studies reported on N staging (865 patients), and 1 study reported on M staging (79 patients). For T staging, our metaanalyses of extraprostatic extension on a patient level based on 3 studies revealed a pooled sensitivity of 54% (95% CI, 46%-63%) and a pooled specificity of 92% (95% CI, 76%-98%). For N staging, our metaanalyses on detection of lymph node metastases on a patient level based on 5 studies revealed a pooled sensitivity of 42% (95% CI, 28%-57%) and a pooled specificity of 94% (95% CI, 90%-97%). In terms of sensitivity for M staging on a patient level, [¹⁸F]PSMA-1007 PET/CT outperformed all other tested conventional imaging modalities. Conclusion: PET/CT imaging with [¹⁸F]PSMA-1007 provides high sensitivity and specificity in T, N, and M staging of PCa when compared with histopathology. It offers the possibility to perform noninvasive primary T, N, and M staging before treatment in a single procedure.

Fibroblast activation protein (FAP) has been proposed as a pan-tumor target for PET imaging using FAP-targeted tracers. Here, we explore the potential value of FAP PET in renal tumors. Methods: Six patients with renal tumors (4 with clear cell renal cell carcinoma, 1 with papillary renal cell carcinoma, and 1 with renal oncocytoma) who were included in a prospective imaging study (NCT04147494) underwent [⁶⁸Ga]Ga-FAPI-46 PET before nephrectomy. FAP PET radiotracer uptake and FAP expression by immunohistochemistry were assessed in the tumors and surrounding renal parenchyma. Results: Tumoral FAP radiotracer uptake was highest in clear cell renal cell carcinoma (median SUV_max, 3.1; range, 2.5-5.3), followed by renal oncocytoma (SUV_max, 1.9) and papillary renal cell carcinoma (SUV_max, 1.1). The FAP PET signal strongly correlated with FAP expression by immunohistochemistry (SUV_max; r = 0.93; P = 0.007). Conclusion: FAP expression in different renal tumors, including renal cell carcinoma, was lower when compared with cancers with known FAP expression, such as sarcoma. Although our data do not favor FAP-based theranostic approaches in renal cell carcinoma, studies in larger cohorts are warranted for conclusive evidence.