Noninvasive Assessment of Human Epidermal Growth Factor Receptor 2 (HER2) in Esophagogastric Cancer Using 89Zr-Trastuzumab PET: A Pilot Study.

Variations in human epidermal growth factor receptor 2 (HER2) expression between the primary tumor and metastases may contribute to drug resistance in HER2-positive (HER2+) metastatic esophagogastric cancer (mEGC). 89Zr-trastuzumab PET (HER2 PET) holds promise for noninvasive assessment of variations in HER2 expression and target engagement. The aim of this study was to describe HER2 PET findings in patients with mEGC. Methods: Patients with HER2+ mEGC were imaged with HER2 PET, 18F-FDG PET, and CT. Lesions were annotated using measurements (on CT) and maximum SUVs (on HER2 PET). Correlation of visualized disease burden among imaging modalities with clinical and pathologic characteristics was performed. Results: Thirty-three patients with HER2+ mEGC were imaged with HER2 PET and CT (12% esophageal, 64% gastroesophageal junction, and 24% gastric adenocarcinoma), 26 of whom were also imaged with 18F-FDG PET. More lesions were identified on 18F-FDG PET (median, 7 [range, 1-14]) than HER2 PET (median, 4 [range, 0-11]). Of the 8 lesions identified on HER2 but not on 18F-FDG PET, 3 (38%) were in bone and 1 was in the brain. Of the 68 lesions identified on 18F-FDG but not on HER2 PET, 4 (6%) were in bone and the remainder were in the lymph nodes (35, 51%) and liver (16, 24%). Of the 33 total patients, 23 (70%) were HER2 imaging-positive (≥50% of tumor load positive). Only 10 patients had 100% of the tumor load positive; 2 had 0% positive. When only patients receiving HER2-directed therapy as first-line treatment were considered (n = 13), median progression-free survival (PFS) therapy was not significantly different between HER2 imaging-positive and -negative patients. Median PFS for patients with at least 1 intense or very intense lesion (SUV ≥ 10) was 16 (95% CI: 11-not reached) mo (n = 7), compared with 12 (95% CI: 6.3-not reached) mo for patients without an intense or very intense lesion (n = 6) (P = 0.35). Conclusion: HER2 PET may identify heterogeneity of HER2 expression and allow assessment of lesions throughout the entire body. A potential application of HER2 PET is noninvasive evaluation of HER2 status including assessment of intrapatient disease heterogeneity not captured by standard imaging or single-site biopsies.

Assessment of salivary gland function after 177Lu-PSMA radioligand therapy: Current concepts in imaging and management.

Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate epithelial cells and is strongly upregulated in prostate cancer. Radioligand therapy using beta-emitting Lutetium-177 (177Lu)-labeled-PSMA-617, a radiolabeled small molecule, has gained attention as a novel targeted therapy for metastatic prostate cancer, given its high affinity and long tumor retention, and rapid blood pool clearance. In March 2022, the United States Food and Drug administration has granted approval to the targeted 177Lu-PSMA-617 therapy for treatment of patients with PSMA-positive metastatic castration resistant prostate cancer, who have been previously treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy. Studies have demonstrated the adverse effects of this treatment, mainly encountered due to radiation exposure to non-target tissues. Salivary glands show high PSMA-ligand uptake and receive increased radiation dose secondary to accumulation of 177Lu-PSMA-617. This predisposes the glands to radiation-mediated toxicity. The exact mechanism, scope and severity of radiation-mediated salivary gland toxicity are not well understood, however, the strategies for its prevention and treatment are under evaluation. This review will focus on the current knowledge about salivary gland impairment post 177Lu labeled PSMA-based radioligand therapies, diagnostic methodologies, and imaging with emphasis on salivary gland scintigraphy. The preventive strategies and known treatment options would also be briefly highlighted.

Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.

PURPOSE: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer. PATIENTS AND METHODS: In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT. RESULTS: Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells. CONCLUSIONS: Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.

Functional Imaging Methods for Assessment of Minimal Residual Disease in Multiple Myeloma: Current Status and Novel ImmunoPET Based Methods.

Imaging plays a key role in assessment of myeloma. Osteolytic bone lesions are optimally assessed using structural imaging, however the structural changes lag the functional changes in the disease. Functional imaging with fluoro deoxy glucose (FDG) positron emission tomography (PET) computerized tomography (CT) is useful in assessment of high-risk myeloma. FDG PET provides prognostic information and is helpful in monitoring response to therapy. However, it is nonspecific and may not be optimal in assessing treatment response to immunotherapeutic agents. Imaging with targeted agents may allow for better assessment of changes from therapy, that is based on the specific targeted mechanism. ImmunoPET imaging is a novel method to assess targeting of specific antigen by therapeutic antibodies. This review summarizes the role of functional imaging and development of novel immunoPET agents for assessment of treatment response and residual disease.

Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I-MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.

PURPOSE: To evaluate detailed organ-based radiation-absorbed dose for planning double high-dose treatment with I-MIBG. METHODS: In a prospective study, 33 patients with high-risk refractory or recurrent neuroblastoma were treated with high-dose I-MIBG. Organ dosimetry was estimated from the first I-MIBG posttherapy imaging and from subsequent I-MIBG imaging prior to the planned second administration. Three serial whole-body scans were performed per patient 2 to 6 days after I-MIBG therapy (666 MBq/kg or 18 mCi/kg) and approximately 0.5, 24, and 48 hours after the diagnostic I-MIBG dose (370 MBq/kg or 10 mCi/1.73 m). Organ radiation doses were calculated using OLINDA. I-MIBG scan dosimetry estimations were used to predict doses for the second I-MIBG therapy and compared with I-MIBG posttherapy estimates. RESULTS: Mean ± SD whole-body doses from I-MIBG and I-MIBG scans were 0.162 ± 112 and 0.141 ± 0.068 mGy/MBq, respectively. I-MIBG and I-MIBG organ doses were variable-generally higher for I-MIBG-projected doses than those projected using posttherapy I-MIBG scans. Mean ± SD doses to liver, heart wall, and lungs were 0.487 ± 0.28, 0.225 ± 0.20, and 0.40 ± 0.26, respectively, for I-MIBG and 0.885 ± 0.56, 0.618 ± 0.37, and 0.458 ± 0.56, respectively, for I-MIBG. Mean ratio of I-MIBG to I-MIBG estimated radiation dose was 1.81 ± 1.95 for the liver, 2.75 ± 1.84 for the heart, and 1.13 ± 0.93 for the lungs. No unexpected toxicities were noted based on I-MIBG-projected doses and cumulative dose limits of 30, 20, and 15 Gy to liver, kidneys, and lungs, respectively. CONCLUSIONS: For repeat I-MIBG treatment planning, both I-MIBG and I-MIBG imaging yielded variable organ doses. However, I-MIBG-based dosimetry yielded a more conservative estimate of maximum allowable activity and would be suitable for planning and limiting organ toxicity with repeat high-dose therapies.

A comparison of pediatric and adult CT organ dose estimation methods.

BACKGROUND: Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation. METHODS: Five age groups of pediatric patients and adult patients were simulated by three organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans were simulated, and doses to organs both inside and outside the scan range were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo. For pediatric patients, VirtualDose was compared to CT-Expo and compared to size-based methods from literature. Pediatric to adult effective dose ratios were also calculated with VirtualDose, and were compared with the ranges of effective dose ratios provided in ImPACT. RESULTS: In-field organs see less than 60% difference in dose between dose estimators. For organs outside scan range or distributed organs, a five times' difference can occur. VirtualDose agrees with the size-based methods within 20% difference for the organs investigated. Between VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are compared, and less than 21% difference is observed for chest scan while more than 40% difference is observed for head-neck scan and abdomen-pelvis scan. For pediatric patients, 2 cm scan range change can lead to a five times dose difference in partially scanned organs. CONCLUSIONS: VirtualDose is validated against CT-Expo and ImPACT with relatively small discrepancies in dose for organs inside scan range, while large discrepancies in dose are observed for organs outside scan range. Patient-specific organ dose estimation is possible using the size-based methods, and VirtualDose agrees with size-based method for the organs investigated. Careful range selection for CT protocols is necessary for organ dose optimization for pediatric and adult patients.