Kairemo Kalevi, Kangasmäki Aki, Kappadath Srinivasan Cheenu, Joensuu Timo, Macapinlac Homer A
Department of Theragnostics, Docrates Cancer Center, 00180 Helsinki, Finland.
Department of Nuclear Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
Life (Basel). 2022 Nov 25;12(12):1977. doi: 10.3390/life12121977.
Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). The bone regions in CT were used to coregister the two PET/CT scans. The whole skeleton volume(s) of interest (VOIs) were defined using the CT component of PET (HU > 150); similarly, the sclerotic/dense bone was defined as HU > 600. Additional VOIs were defined for PET, with pathological threshold values for PSMA (SUV > 3.0) and NaF (SUV > 10). Besides the pathological bone volumes measured with each technique (CT, NaF, and PSMA-PET) and their contemporaneous combinations, overlapping VOIs with the CT-based skeletal and sclerotic volumes were also recorded. Additionally, thresholds of 4.0, 6.0, and 10.0 were tested for SUVPSMA. Results: In group M, the skeletal VOI volumes were 8.77 ± 1.80 L, and the sclerotic bone volumes were 1.32 ± 0.50 L; in contrast, in group N, they were 8.73 ± 1.43 L (skeletal) and 1.23 ± 0.28 L (sclerosis). The total enzyme activity for PSMA was 2.21 ± 5.15 in the M group and 0.078 ± 0.053 in the N group (p < 0.0002). The total bone demineralization activity for NaF varied from 4.31 ± 6.17 in the M group and 0.24 ± 0.56 in group N (p < 0.0002). The pathological PSMA volume represented 0.44−132% of the sclerotic bone volume in group M and 0.55−2.3% in group N. The pathological NaF volume in those patients with multiple metastases represented 0.27−68% of the sclerotic bone volume, and in the control group, only 0.00−6.5% of the sclerotic bone volume (p < 0.0003). Conclusions: These results confirm our earlier findings that CT alone does not suit the evaluation of the extent of active skeletal metastases in PCa. PSMA and NaF images give complementary information about the extent of the active skeletal disease, which has a clinical impact and may change its management. The PSMA and NaF absolute volumes could be used for planning targeted therapies. A cut-off value 3.0 for SUVPSMA given here is the best correlation in the presentation of active metastatic skeletal disease.
骨是前列腺癌（PCa）最常见的转移部位。68Ga-PSMA-11（或戈泽托肽）和氟化钠-18（Na18F）是用于评估PCa相关骨转移的较新放射性药物。戈泽托肽摄取反映细胞膜酶活性，而氟化钠摄取测量晚期PCa中的骨矿化。在此，我们旨在表征这种差异，并可能为靶向治疗中的患者选择提供一种新方法。方法：该研究包括14例晚期PCa患者（M组，>5个病灶），他们在连续几天内分别接受了PSMA和NaF的常规PET/CT检查，以及12例无骨转移的PCa患者（N组）。利用CT中的骨区域对两次PET/CT扫描进行配准。使用PET的CT成分（HU>150）定义全骨骼感兴趣体积（VOIs）；同样，将硬化/致密骨定义为HU>600。为PET定义了额外的VOIs，PSMA（SUV>3.0）和NaF（SUV>10）的病理阈值。除了用每种技术（CT、NaF和PSMA-PET）测量的病理骨体积及其同期组合外，还记录了与基于CT的骨骼和硬化体积重叠的VOIs。此外，还测试了SUVPSMA的4.0、6.0和10.0阈值。结果：在M组中，骨骼VOI体积为8.77±1.80L，硬化骨体积为1.32±0.50L；相比之下，在N组中，骨骼VOI体积为8.73±1.43L，硬化骨体积为1.23±0.28L。M组中PSMA的总酶活性为2.21±5.15，N组为0.078±0.053（p<0.0002）。M组中NaF的总骨脱矿活性为4.31±6.17，N组为0.24±0.56（p<0.0002）。M组中病理PSMA体积占硬化骨体积的0.44%-132%，N组为0.55%-2.3%。多发转移患者中病理NaF体积占硬化骨体积的0.27%-68%，而在对照组中，仅占硬化骨体积的0.00%-6.5%（p<0.0003）。结论：这些结果证实了我们早期的发现，即单独的CT不适合评估PCa中活动性骨转移的范围。PSMA和NaF图像提供了关于活动性骨骼疾病范围的补充信息，这具有临床意义并可能改变其治疗管理。PSMA和NaF的绝对体积可用于规划靶向治疗。此处给出的SUVPSMA截止值3.0在活动性转移性骨骼疾病的呈现中具有最佳相关性。
