How Long of a Dynamic 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET Acquisition Is Needed for Robust Kinetic Analysis in Breast Cancer?
- 93 Downloads
To quantitatively evaluate the minimally required scanning time of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) dynamic acquisition for accurate kinetic assessment of the proliferation in breast cancer tumors.
Within a therapeutic intervention trial, 26 breast tumors of 8 breast cancer patients were analyzed from 30-min dynamic [18F]FLT-PET acquisitions. PET/CT was acquired on a Gemini TF 64 system (Philips Healthcare) and reconstructed into 26 frames (8 × 15 s, 6 × 30 s, 5 × 1 min, 5 × 2 min, and 2 × 5 min). Maximum activity concentrations (Bq/ml) of volume of interests over tumors and plasma in descending aorta were obtained over time frames. Kinetic parameters were estimated using in-house developed software with the two-tissue three-compartment irreversible model (2TCM) (K1, k2, k3, and Ki; k4 = 0) and Patlak model (Ki) based on different acquisition durations (Td) (10, 12, 14, 16, 20, 25, and 30 min, separately). Different linear regression onset time (T0) points (1, 2, 3, 4, and 5 min) were applied in Patlak analysis. Ki of the 30-min data set was taken as the gold standard for comparison. Pearson product-moment correlation coefficient (R) of 0.9 was chosen as a limit for the correlation.
The correlation of kinetic parameters between the gold standard and the abbreviated dynamic data series increased with longer Td from 10 to 30 min. k2 and k3 using 2TCM and Ki using Patlak model revealed poor correlations for dynamic PET with Td ≤ 14 min (k2: R = 0.84, 0.85, 0.86; k3: R = 0.67, 0.67, 0.67; Ki: R = 0.72, 0.78, 0.87 at Td = 10, 12, and 14 min, respectively). Excellent correlations were shown for all kinetic parameters when Td ≥ 16 min regardless of the kinetic model and T0 value (R > 0.9).
This study indicates that a 16-min dynamic PET acquisition appears to be sufficient to provide accurate [18F]FLT kinetics to quantitatively assess the proliferation in breast cancer lesions.
Key words3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) Kinetic modeling Dynamic PET Breast Cancer Acquisition duration
The authors acknowledge the help from Preethi Subramanian M.S. for the [18F]FLT data management.
This project was financially supported by NCI grant U01CA076576, Ohio Third Frontier ODSA TECH09-028, and the Wright Center of Innovation Development Fund.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 1.American Cancer Society. Breast cancer facts & figures 2017–2018 (2017) Atlanta: American Cancer Society, Inc. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf
- 7.Smith IC, Welch AE, Hutcheon AW, Miller ID, Payne S, Chilcott F, Waikar S, Whitaker T, Ah-See AK, Eremin O, Heys SD, Gilbert FJ, Sharp PF (2000) Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 18:1676–1688CrossRefGoogle Scholar
- 12.Kenny L, Coombes RC, Vigushin DM, al-Nahhas A, Shousha S, Aboagye EO (2007) Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging 34:1339–1347CrossRefGoogle Scholar
- 17.Muzi M, Vesselle H, Grierson JR, Mankoff DA, Schmidt RA, Peterson L, Wells JM, Krohn KA (2005) Kinetic analysis of 3′-deoxy-3′-fluorothymidine PET studies: validation studies in patients with lung cancer. J Nucl Med 46:274–282Google Scholar
- 21.Gaeta CM, Vercher-Conejero JL, Sher AC, Kohan A, Rubbert C, Avril N (2013) Recurrent and metastatic breast cancer PET, PET/CT, PET/MRI: FDG and new biomarkers. Q J Nucl Med Mol Imaging 57:352–366Google Scholar
- 26.Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM, Doot RK, Lawton TJ, Barlow WE, Kurland BF, Schubert EK, Mankoff DA (2008) Tumor metabolism and blood flow changes by positron emission tomography: relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol 26:4449–4457CrossRefGoogle Scholar
- 27.Dunnwald LK, Doot RK, Specht JM, Gralow JR, Ellis GK, Livingston RB, Linden HM, Gadi VK, Kurland BF, Schubert EK, Muzi M, Mankoff DA (2011) PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake. Clin Cancer Res 17:2400–2409CrossRefGoogle Scholar
- 31.Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Charlop A, Lawton TJ, Schubert EK, Tseng J, Livingston RB (2002) Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 43:500–509Google Scholar
- 32.Desilva A, Wuest M, Wang M, Hummel J, Mossman K, Wuest F, Hitt MM (2012) Comparative functional evaluation of immunocompetent mouse breast cancer models established from PyMT-tumors using small animal PET with [18F]FDG and [18F]FLT. Am J Nucl Med Mol Imaging 2:88–98Google Scholar
- 34.Kramer GM, Frings V, Heijtel D, Smit EF, Hoekstra OS, Boellaard R, QuIC-ConCePT Consortium (2017) Parametric method performance for dynamic 3′-deoxy-3'-18F-fluorothymidine PET/CT in epidermal growth factor receptor-mutated non-small cell lung carcinoma patients before and during therapy. J Nucl Med 58:920–925CrossRefGoogle Scholar