68 Ga-FAPI PET/CT: Biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers

Frederik L. Giesel, Clemens Kratochwil, Thomas Lindner, Manfred M. Marschalek, Anastasia Loktev, Wencke Lehnert, Jürgen Debus, Dirk Jäger, Paul Flechsig, Annette Altmann, Walter Mier, Uwe Haberkorn

Research output: Contribution to journalArticle

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Abstract

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts of several tumor entities. The recent development of quinoline-based PET tracers that act as FAP inhibitors (FAPIs) demonstrated promising results preclinically and already in a few clinical cases. Consequently, these tracers are now applied in our hospital to amend the diagnostics of cancer patients facing the limitations of standard examinations. Here, we analyze the tissue biodistribution and preliminary dosimetry of 2 members of this new class of PET radiopharmaceutical. Methods: A preliminary dosimetry estimate for 68 Ga-FAPI-2 and 68 Ga-FAPI-4 was based on 2 patients examined at 0.2, 1, and 3 h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either 68 Ga-FAPI-2 (n 5 25) or 68 Ga-FAPI-4 (n 5 25); for 6 patients an intraindividual related 18 F-FDG scan (also acquired 1 h after injection) was available. For the normal tissue of 16 organs, a 2-cm spheric volume of interest was placed in the parenchyma; for tumor lesions, a threshold-segmented volume of interest was used to quantify SUV mean and SUV max . Results: Similar to literature values for 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11, an examination with 200 MBq of 68 Ga-FAPI-2 o 68 Ga-FAPI-4 corresponds to an equivalent dose of approximately 3–4 mSv. After a fast clearance via the kidneys, the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h after injection. In 68 Ga-FAPI-2, the tumor uptake from 1 to 3 h after injection decreased by 75%, whereas the tumor retention was prolonged with 68 Ga-FAPI-4 (25% washout). Regarding tumor-to-background ratios, at 1 h after injection both 68 Ga-FAPI tracers performed equally. In comparison to 18 F-FDG, the tumor uptake was almost equal (average SUV max , 7.41 for 18 F-FDG and 7.37 for 68 Ga-FAPI-2; not statistically significant); the background uptake in brain (11.01 vs. 0.32), liver (2.77 vs. 1.69), and oral/pharyngeal mucosa(4.88 vs. 2.57) was significantly lowerwith 68 Ga-FAPI. Other organs did not relevantly differ between 18 F-FDG and 68 Ga-FAPI. Conclusion: FAPI PET/CT is a new diagnostic method in imaging cancer patients. In contrast to 18 F-FDG, no diet or fasting in preparation for the examination is necessary, and image acquisition can potentially be started a few minutes after tracer application. Tumor-to background contrast ratios were equal to or even better than those of 18 F-FDG.

Original languageEnglish (US)
Pages (from-to)386-392
Number of pages7
JournalJournal of Nuclear Medicine
Volume60
Issue number3
DOIs
StatePublished - Jan 1 2019

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Protein Transport
Fibroblasts
Neoplasms
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Radiopharmaceuticals
Mouth Mucosa
Fasting
Proteins
Software
Diet
Kidney
Liver
Brain

Keywords

  • Biodistribution
  • Cancer-associated fibroblasts
  • Dosimetry
  • Fibroblast activation protein
  • PET/CT
  • Radiotracer tissue kinetics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

68 Ga-FAPI PET/CT : Biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. / Giesel, Frederik L.; Kratochwil, Clemens; Lindner, Thomas; Marschalek, Manfred M.; Loktev, Anastasia; Lehnert, Wencke; Debus, Jürgen; Jäger, Dirk; Flechsig, Paul; Altmann, Annette; Mier, Walter; Haberkorn, Uwe.

In: Journal of Nuclear Medicine, Vol. 60, No. 3, 01.01.2019, p. 386-392.

Research output: Contribution to journalArticle

Giesel, FL, Kratochwil, C, Lindner, T, Marschalek, MM, Loktev, A, Lehnert, W, Debus, J, Jäger, D, Flechsig, P, Altmann, A, Mier, W & Haberkorn, U 2019, '68 Ga-FAPI PET/CT: Biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers' Journal of Nuclear Medicine, vol. 60, no. 3, pp. 386-392. https://doi.org/10.2967/jnumed.118.215913
Giesel, Frederik L. ; Kratochwil, Clemens ; Lindner, Thomas ; Marschalek, Manfred M. ; Loktev, Anastasia ; Lehnert, Wencke ; Debus, Jürgen ; Jäger, Dirk ; Flechsig, Paul ; Altmann, Annette ; Mier, Walter ; Haberkorn, Uwe. / 68 Ga-FAPI PET/CT : Biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. In: Journal of Nuclear Medicine. 2019 ; Vol. 60, No. 3. pp. 386-392.
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abstract = "Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts of several tumor entities. The recent development of quinoline-based PET tracers that act as FAP inhibitors (FAPIs) demonstrated promising results preclinically and already in a few clinical cases. Consequently, these tracers are now applied in our hospital to amend the diagnostics of cancer patients facing the limitations of standard examinations. Here, we analyze the tissue biodistribution and preliminary dosimetry of 2 members of this new class of PET radiopharmaceutical. Methods: A preliminary dosimetry estimate for 68 Ga-FAPI-2 and 68 Ga-FAPI-4 was based on 2 patients examined at 0.2, 1, and 3 h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either 68 Ga-FAPI-2 (n 5 25) or 68 Ga-FAPI-4 (n 5 25); for 6 patients an intraindividual related 18 F-FDG scan (also acquired 1 h after injection) was available. For the normal tissue of 16 organs, a 2-cm spheric volume of interest was placed in the parenchyma; for tumor lesions, a threshold-segmented volume of interest was used to quantify SUV mean and SUV max . Results: Similar to literature values for 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11, an examination with 200 MBq of 68 Ga-FAPI-2 o 68 Ga-FAPI-4 corresponds to an equivalent dose of approximately 3–4 mSv. After a fast clearance via the kidneys, the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h after injection. In 68 Ga-FAPI-2, the tumor uptake from 1 to 3 h after injection decreased by 75{\%}, whereas the tumor retention was prolonged with 68 Ga-FAPI-4 (25{\%} washout). Regarding tumor-to-background ratios, at 1 h after injection both 68 Ga-FAPI tracers performed equally. In comparison to 18 F-FDG, the tumor uptake was almost equal (average SUV max , 7.41 for 18 F-FDG and 7.37 for 68 Ga-FAPI-2; not statistically significant); the background uptake in brain (11.01 vs. 0.32), liver (2.77 vs. 1.69), and oral/pharyngeal mucosa(4.88 vs. 2.57) was significantly lowerwith 68 Ga-FAPI. Other organs did not relevantly differ between 18 F-FDG and 68 Ga-FAPI. Conclusion: FAPI PET/CT is a new diagnostic method in imaging cancer patients. In contrast to 18 F-FDG, no diet or fasting in preparation for the examination is necessary, and image acquisition can potentially be started a few minutes after tracer application. Tumor-to background contrast ratios were equal to or even better than those of 18 F-FDG.",
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TY - JOUR

T1 - 68 Ga-FAPI PET/CT

T2 - Biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers

AU - Giesel, Frederik L.

AU - Kratochwil, Clemens

AU - Lindner, Thomas

AU - Marschalek, Manfred M.

AU - Loktev, Anastasia

AU - Lehnert, Wencke

AU - Debus, Jürgen

AU - Jäger, Dirk

AU - Flechsig, Paul

AU - Altmann, Annette

AU - Mier, Walter

AU - Haberkorn, Uwe

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts of several tumor entities. The recent development of quinoline-based PET tracers that act as FAP inhibitors (FAPIs) demonstrated promising results preclinically and already in a few clinical cases. Consequently, these tracers are now applied in our hospital to amend the diagnostics of cancer patients facing the limitations of standard examinations. Here, we analyze the tissue biodistribution and preliminary dosimetry of 2 members of this new class of PET radiopharmaceutical. Methods: A preliminary dosimetry estimate for 68 Ga-FAPI-2 and 68 Ga-FAPI-4 was based on 2 patients examined at 0.2, 1, and 3 h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either 68 Ga-FAPI-2 (n 5 25) or 68 Ga-FAPI-4 (n 5 25); for 6 patients an intraindividual related 18 F-FDG scan (also acquired 1 h after injection) was available. For the normal tissue of 16 organs, a 2-cm spheric volume of interest was placed in the parenchyma; for tumor lesions, a threshold-segmented volume of interest was used to quantify SUV mean and SUV max . Results: Similar to literature values for 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11, an examination with 200 MBq of 68 Ga-FAPI-2 o 68 Ga-FAPI-4 corresponds to an equivalent dose of approximately 3–4 mSv. After a fast clearance via the kidneys, the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h after injection. In 68 Ga-FAPI-2, the tumor uptake from 1 to 3 h after injection decreased by 75%, whereas the tumor retention was prolonged with 68 Ga-FAPI-4 (25% washout). Regarding tumor-to-background ratios, at 1 h after injection both 68 Ga-FAPI tracers performed equally. In comparison to 18 F-FDG, the tumor uptake was almost equal (average SUV max , 7.41 for 18 F-FDG and 7.37 for 68 Ga-FAPI-2; not statistically significant); the background uptake in brain (11.01 vs. 0.32), liver (2.77 vs. 1.69), and oral/pharyngeal mucosa(4.88 vs. 2.57) was significantly lowerwith 68 Ga-FAPI. Other organs did not relevantly differ between 18 F-FDG and 68 Ga-FAPI. Conclusion: FAPI PET/CT is a new diagnostic method in imaging cancer patients. In contrast to 18 F-FDG, no diet or fasting in preparation for the examination is necessary, and image acquisition can potentially be started a few minutes after tracer application. Tumor-to background contrast ratios were equal to or even better than those of 18 F-FDG.

AB - Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts of several tumor entities. The recent development of quinoline-based PET tracers that act as FAP inhibitors (FAPIs) demonstrated promising results preclinically and already in a few clinical cases. Consequently, these tracers are now applied in our hospital to amend the diagnostics of cancer patients facing the limitations of standard examinations. Here, we analyze the tissue biodistribution and preliminary dosimetry of 2 members of this new class of PET radiopharmaceutical. Methods: A preliminary dosimetry estimate for 68 Ga-FAPI-2 and 68 Ga-FAPI-4 was based on 2 patients examined at 0.2, 1, and 3 h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either 68 Ga-FAPI-2 (n 5 25) or 68 Ga-FAPI-4 (n 5 25); for 6 patients an intraindividual related 18 F-FDG scan (also acquired 1 h after injection) was available. For the normal tissue of 16 organs, a 2-cm spheric volume of interest was placed in the parenchyma; for tumor lesions, a threshold-segmented volume of interest was used to quantify SUV mean and SUV max . Results: Similar to literature values for 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11, an examination with 200 MBq of 68 Ga-FAPI-2 o 68 Ga-FAPI-4 corresponds to an equivalent dose of approximately 3–4 mSv. After a fast clearance via the kidneys, the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h after injection. In 68 Ga-FAPI-2, the tumor uptake from 1 to 3 h after injection decreased by 75%, whereas the tumor retention was prolonged with 68 Ga-FAPI-4 (25% washout). Regarding tumor-to-background ratios, at 1 h after injection both 68 Ga-FAPI tracers performed equally. In comparison to 18 F-FDG, the tumor uptake was almost equal (average SUV max , 7.41 for 18 F-FDG and 7.37 for 68 Ga-FAPI-2; not statistically significant); the background uptake in brain (11.01 vs. 0.32), liver (2.77 vs. 1.69), and oral/pharyngeal mucosa(4.88 vs. 2.57) was significantly lowerwith 68 Ga-FAPI. Other organs did not relevantly differ between 18 F-FDG and 68 Ga-FAPI. Conclusion: FAPI PET/CT is a new diagnostic method in imaging cancer patients. In contrast to 18 F-FDG, no diet or fasting in preparation for the examination is necessary, and image acquisition can potentially be started a few minutes after tracer application. Tumor-to background contrast ratios were equal to or even better than those of 18 F-FDG.

KW - Biodistribution

KW - Cancer-associated fibroblasts

KW - Dosimetry

KW - Fibroblast activation protein

KW - PET/CT

KW - Radiotracer tissue kinetics

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