6 results on '"Larson, Steven M."'
Search Results
2. Toward individualized dosimetry for radiopharmaceutical therapy in day-to-day clinical practice of nuclear oncology: overcoming heterogeneity of radiation-absorbed dose to tumor and critical organs
- Author
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Bodei, Lisa, Michael Tuttle, R., Grewal, Ravinder K., Mauguen, Audrey, Augensen, Finn, Abusamra, Murad, Mahajan, Sonia, Jayaprakasam, Vetri Sudar, Osborne, Joseph R., Haque, Sofia, Wong, Bernadette Z. Y., Ghossein, Ronald A., Fagin, James, Schӧder, Heiko, Ho, Alan, Humm, John L., and Larson, Steven M.
- Published
- 2024
- Full Text
- View/download PDF
3. [18F]TFB PET/CT misses intense [124I]iodine-avid metastases after redifferentiation therapy in metastatic thyroid cancer.
- Author
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Backhaus, Philipp, Pentlow, Keith S., Ho, Alan L, Mauguen, Audrey, Fagin, James A, Pillarsetty, Naga Vara Kishore, Lyashchenko, Serge K., Burnazi, Eva, Ghossein, Ronald A., Chhabra, Shalini, Abusamra, Murad, Larson, Steven M., Schöder, Heiko, O'Donoghue, Joseph, Weber, Wolfgang, and Grewal, Ravinder K.
- Subjects
THYROID cancer ,IODINE isotopes ,RANK correlation (Statistics) ,METASTASIS ,IODINE ,TETRAFLUOROBORATES - Abstract
Background: Fluorine 18-labelled tetrafluoroborate ([
18 F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [18 F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [18 F]TFB and compare its properties to [124 I]IodinePET/CT in patients with metastatic thyroid cancer. Methods: Five patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [18 F]TFB and were given 230 ± 9 MBq [124 I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [124 I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [18 F]TFB and [124 I]Iodine were calculated. Results: Three patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [18 F]TFB and 30 (91%) on [124 I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [124 I]Iodine PET/CT with a median SUVmax of 3.3 (range, 0.4–285.0). All of these lesions were [18 F]TFB-negative. Conclusion: [18 F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer. Trial registration number: NCT03196518, registered on June 22, 2017. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
4. Patient metabolic profile defined by liver and muscle 18F-FDG PET avidity is independently associated with overall survival in gastric cancer.
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Vitiello, Gerardo A., Jayaprakasam, Vetri Sudar, Tang, Laura H., Schattner, Mark A., Janjigian, Yelena Y., Ku, Geoffrey Y., Maron, Steven B., Schoder, Heiko, Larson, Steven M., Gönen, Mithat, Datta, Jashodeep, Coit, Daniel G., Brennan, Murray F., and Strong, Vivian E.
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STOMACH cancer ,OVERALL survival ,RECTUS femoris muscles ,POSITRON emission tomography computed tomography ,LIVER ,CANCER patients - Abstract
Background: PET–CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care. Methods: Staging PET–CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET–CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUV
mean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan–Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS. Results: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET–CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56–0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009). Conclusions: Elevated LRF ratio, a patient-specific PET–CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer. [ABSTRACT FROM AUTHOR]- Published
- 2024
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5. [ 18 F]TFB PET/CT misses intense [ 124 I]iodine-avid metastases after redifferentiation therapy in metastatic thyroid cancer.
- Author
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Backhaus P, Pentlow KS, Ho AL, Mauguen A, Fagin JA, Pillarsetty NVK, Lyashchenko SK, Burnazi E, Ghossein RA, Chhabra S, Abusamra M, Larson SM, Schöder H, O'Donoghue J, Weber W, and Grewal RK
- Abstract
Background: Fluorine 18-labelled tetrafluoroborate ([
18 F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [18 F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [18 F]TFB and compare its properties to [124 I]IodinePET/CT in patients with metastatic thyroid cancer., Methods: Five patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [18 F]TFB and were given 230 ± 9 MBq [124 I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [124 I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [18 F]TFB and [124 I]Iodine were calculated., Results: Three patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [18 F]TFB and 30 (91%) on [124 I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [124 I]Iodine PET/CT with a median SUVmax of 3.3 (range, 0.4-285.0). All of these lesions were [18 F]TFB-negative., Conclusion: [18 F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer., Trial Registration Number: NCT03196518, registered on June 22, 2017., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
6. Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177 Lu-Labeled Radiohapten.
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Vaughn BA, Lee SG, Vargas DB, Seo S, Rinne SS, Xu H, Guo HF, Le Roux AB, Gajecki L, Krebs S, Yang G, Ouerfelli O, Zanzonico PB, Fung EK, St Jean S, Carrasco SE, Jungbluth A, Cheung NKV, Larson SM, Veach DR, and Cheal SM
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- Animals, Mice, Humans, Tissue Distribution, Cell Line, Tumor, Isotope Labeling, Theranostic Nanomedicine methods, Radiopharmaceuticals therapeutic use, Radiopharmaceuticals pharmacokinetics, Radiopharmaceuticals chemistry, Female, Heterocyclic Compounds, 1-Ring chemistry, Membrane Glycoproteins, Radioimmunotherapy methods, Lutetium, Colorectal Neoplasms radiotherapy, Colorectal Neoplasms diagnostic imaging, Radioisotopes therapeutic use, Radioisotopes chemistry
- Abstract
Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope
177 Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S -2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177 Lu]Lu-Gemini was prepared with no-carrier-added177 LuCl3 to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-177 Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177 Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177 Lu]Lu- S -2-(4-aminobenzyl)-DOTA ([177 Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177 Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [177 Lu]Lu-Gemini behaved similarly to [177 Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177 Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177 Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177 Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177 Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177 Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177 Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177 Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177 Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177 Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered177 Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30)., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2024
- Full Text
- View/download PDF
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