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

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.