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Selective RET inhibitors, such as selpercatinib and pralsetinib, have revolutionized the treatment of cancers with RET gene alterations. These inhibitors have shown remarkable clinical efficacy, particularly in RET-driven lung cancer, medullary thyroid cancer, and other solid tumors driven by RET gene fusions. The assessment of treatment response in oncology has been greatly enhanced by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), a valuable tool that measures tumor metabolism and provides early indicators of treatment effectiveness. This work explores the effectiveness of selective RET inhibitors in targeting RET-positive cancers and investigates the utility of FDG-PET in assessing treatment response. The paper includes insightful case studies that highlight the successful application of RET inhibitors in the treatment of RET-positive cancers. The findings suggest that FDG-PET has the potential to serve as a non-invasive biomarker for monitoring treatment response in patients with RET-positive cancers. However, further research is required to establish standardized criteria for interpreting FDG-PET scans in the context of selective RET inhibitors and to uncover the broader applications of FDG-PET in precision oncology.

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.

Thirty-one consecutive patients were included in this study who were planned for parathyroidectomy due to primary hyperparathyroidism. They were studied with US, 4D-CT and dual-phase scintigraphy including SPECT/CT, and possible adenomas were identified in each imaging modality. Imaging data were quantified with US, CT and SPECT. Parathyroidectomies were performed as minimally invasive according to preoperative imaging findings. A total of 16 adenomas were found in 15 patients, and the surgery was negative in four patients. The imaging results were compared with each other and correlated to histology findings and blood biochemistry (S-Ca and P-PTH). Quantitative SPECT found a strong correlation between the quantification methods—Conjugate Gradient with Attenuation and Scatter Correction with a zone map (CGZAS) and Conjugate Gradient with Attenuation and Scatter Correction (CGAS)—measured as SUVmax and kBq/mL. However, a statistically significant correlation between the quantitative parameters (CGZAS and CGAS) and serum biomarkers (S-PTH and S-Ca) was not observed. The sensitivities of the imaging methods were calculated using histopathology as a gold standard. SPECT/CT demonstrated 93% sensitivity, 4D-CT 93% sensitivity and ultrasonography 73% sensitivity. The imaging methods were compared with each other using parathyroid regions because findings and locations varied between the modalities. Our prospective study supports that quantitative SPECT/CT is useful for presurgical assessment of primary hyperparathyroidism.

Purpose The development of osteosarcoma therapeutics has been challenging, in part because of the lack of appropriate criteria to evaluate responses. We developed a novel criteria in a clinical trial of radium-223 dichloride (223RaCl2) for response assessment in osteosarcoma, NAFCIST (Na18F PET response Criteria in Solid Tumors).Experimental design Patients received one to six cycles of 223RaCl2, and cumulative doses varied from 6.84 MBq to 57.81 MBq. Molecular imaging with technetium-99m phosphonate scintigraphy, fluorine-18-fluorodeoxyglucose (18FDG) positron emission tomography (PET) or sodium fluoride-18 (Na18F) PET was used to characterise the disease. Correlation of biomarkers and survival was analysed with NAFCIST measure from Na18F PET.Results Of the 18 patients, 17 had bone lesions visible in at least one of the imaging studies. In four of seven patients with multiple skeletal lesions (>5), FDG PET and NaF PET studies could be compared. The skeletal tumour locations varied in our patient population: cranium=2, extremities=7, pelvis=10, spine=12 and thorax=9. The 18F-FDG PET and Na18F PET studies could be compared in all four patients who had multiple lung lesions (>5). Overall the Response Evaluation Criteria in Solid Tumors response was seen in one patient, but four patients experienced mixed responses better defined by Na18F PET. Changes in NAFCIST were correlated with changes in bone alkaline phosphatase levels (r=0.54) and negatively with cumulative dose of 223RaCl2 (r=− 0.53). NAFCIST correlated with overall survival (p value of 0.037) while the PERCIST (PET Response Criteria in Solid Tumors) did not (p value of 0.19).Conclusions Our results indicate that Na18F PET should be further studied in osteosarcoma staging. NAFCIST may be a promising criteria for high-risk osteosarcoma response evaluation and correlates with survival. Further validation studies are needed.

Bone metastases are common in prostate cancer (PCa). Fluorocholine-18 (FCH) and sodium fluoride-18 (NaF) have been used to assess PCa associated skeletal disease in thousands of patients by demonstrating different mechanism of uptake-cell membrane (lipid) synthesis and bone mineralization. Here, this difference is characterized quantitatively in detail. Our study cohort consisted of 12 patients with advanced disease (> 5 lesions) (M) and of five PCa patients with no skeletal disease (N). They had routine PET/CT with FCH and NaF on consecutive days. Skeletal regions in CT were used to co-register the two PET/CT scans. Bone 3-D volume of interest (VOI) was defined on the CT of PET with a threshold of HU > 150, and sclerotic/dense bone as HU > 600, respectively. Additional VOIs were defined on PET uptake with the threshold values on both FCH (SUV > 3.5) and NaF (SUV > 10). The pathologic skeletal volumes for each technique (CT, HU > 600), NaF (SUV > 10) and FCH (SUV > 3.5) were developed and analyzed. The skeletal VOIs varied from 5.03 L to 7.31 L, whereas sclerotic bone VOIs were from 0.88 L to 2.99 L. Total choline kinase (cell membrane synthesis) activity for FCH (TCA) varied from 0.008 to 4.85 [kg] in M group and from 0.0006 to 0.085 [kg] in N group. Total accelerated osteoblastic (bone demineralization) activity for NaF (TBA varied from 0.25 to 13.6 [kg] in M group and varied from 0.000 to 1.09 [kg] in N group. The sclerotic bone volume represented only 1.86 ± 1.71% of the pathologic FCH volume and 4.07 ± 3.21% of the pathologic NaF volume in M group, and only 0.08 ± 0.09% and 0.18 ± 0.19% in N group, respectively. Our results suggest that CT alone cannot be used for the assessment of the extent of active metastatic skeletal disease in PCa. NaF and FCH give complementary information about the activity of the skeletal disease, improving diagnosis and disease staging.

Although 3′-deoxy-3′[(18)F]-fluorothymidine (FLT)-positron emission tomography (PET) has been utilized for tumor response assessment to neoadjuvant chemotherapy in soft tissue sarcomas, it has not been exploited for the assessment of early response to systematically targeted therapies. Herein, we investigated the 18F-FLT PET/CT kinetics in patients with sarcoma who received targeted therapies. Among 15 patients with sarcoma who underwent 18F-FLT PET/CT, 5 patients (33%) patients were imaged at three time points: At baseline and at 1−15 weeks (MDM2-inhibitor treatment), and 10 patients (67%) were imaged twice: At baseline and at 1−4 weeks (MDM2 inhibitor, n = 5; c-met inhibitor n = 5). The patients with sarcoma had a total of 18 identifiable tumors. Twelve of 15 patients (80%) demonstrated 18F-FLT concentrations changes early, i.e., at 1−4 weeks. Eight patients responded (53.3%), four patients progressed (26.7%) based on FLT change of more than 10% increase, and three patients (20%) demonstrated no change. 18F-FLT PET/CT may be used for early response imaging to molecularly targeted therapies in patients with sarcoma. Further larger studies in specific sarcoma sub-types are warranted.

Although 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a sensitive nuclear medicine modality, specificity for characterizing lung cancer is limited. Tumor proliferation and early response to molecularly targeted therapy could be visualized using 3′-deoxy-3′[(18)F]-fluorothymidine (18F-FLT) PET/CT. The superiority of 18F-FLT PET/CT over 18F-FDG PET/CT in early therapeutic monitoring has been well described in patients after chemotherapy, radiotherapy, and/or chemo/radiotherapy. In thispilot study, we explorethe use of 18F-FLT PET/CT as an early response evaluation modality in patients with lung cancerand provide specific case studies of patients with small cell lung cancer and non-small cell lung cancer who received novel targeted therapies. Early response for c-MET inhibitor was observed in four weeks and for MDM2 inhibitor in nine days.

Fluorothymidine is a thymidine analog labeled with fluorine-18 fluorothymidine for positron emission tomography (18F-FLT-PET) imaging. Thymidine is a nucleic acid that is used to build DNA. Fluorine-18 fluorothymidine (18F-FLT) utilizes the same metabolic pathway as does thymidine but has a very low incidence of being incorporated into the DNA (

The objective of the study was to determine the utility of integrated computed tomography / positron emission tomography (CT‐PET) imaging for detecting interval distant metastases and assessing therapeutic response in patients with locally advanced, potentially resectable esophageal carcinoma after neoadjuvant therapy.A retrospective study was performed of 88 patients with potentially resectable esophageal carcinoma who received neoadjuvant therapy before planned surgical resection. CT‐PET before and after completion of neoadjuvant was used for evaluating therapeutic response; response criteria were based on qualitative and semiquantitative analyses.Neoadjuvant therapy comprised chemoradiotherapy in 85 patients, with prior induction chemotherapy in 39 patients. Fifty‐five patients proceeded to esophagectomy. Repeat CT‐PET was performed after induction chemotherapy (n = 23) and after completing chemoradiotherapy (n = 85). CT‐PET identified the interval appearance of metastatic disease in 7 (8%) patients. For assessment of locoregional therapeutic response, CT‐PET was unable to predict pathological response to neoadjuvant therapy in the primary tumor or locoregional lymph nodes. CT‐PET had sensitivity, specificity, and positive and negative predictive values of 57%, 46%, 39%, and 64%, respectively, for detection of residual macroscopic malignancy within the primary tumor; and sensitivity, specificity, and positive and negative predictive values of 0%, 90%, 0%, and 69% for detection of residual malignancy within resected lymph nodes.CT‐PET performed after neoadjuvant therapy in patients with potentially resectable esophageal carcinoma is important for detecting interval metastases that preclude surgical resection, but is of limited utility for assessing locoregional therapeutic response. Cancer 2007. © 2006 American Cancer Society [ABSTRACT FROM AUTHOR]