Pilot pharmacokinetic and dosimetric studies of18F-FPPRGD2: A PET radiopharmaceutical agent for imaging αvβ3 integrin levels

Erik Mittra, Michael L. Goris, Andrei H. Iagaru, Arash Kardan, Lindee Burton, Rhona Berganos, Edwin Chang, Shuanglong Liu, Bin Shen, Frederick T. Chin, Xiaoyuan Chen, Sanjiv S. Gambhir

Research output: Contribution to journalArticle

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Abstract

Purpose: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 (18F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine- aspartic acid (RGD) peptide sequence and targets αvβ 3 integrin, in the first volunteers imaged with this tracer. Materials and Methods: The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/μmol ± 714 [44.4 GBq/μmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistri bution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests. Results: The administration of 18F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/ mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of 18F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096). Conclusion: 18F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients - especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.

Original languageEnglish (US)
Pages (from-to)182-191
Number of pages10
JournalRadiology
Volume260
Issue number1
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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Radiopharmaceuticals
Integrins
Positron-Emission Tomography
Vital Signs
Pharmacokinetics
Reading
Volunteers
Injections
Fluorine
Neoplasm Staging
Research Ethics Committees
Liver Function Tests
Large Intestine
Diaphragm
Salivary Glands
Informed Consent
Aspartic Acid
Brain Neoplasms
Glycine
Radioactivity

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Pilot pharmacokinetic and dosimetric studies of18F-FPPRGD2 : A PET radiopharmaceutical agent for imaging αvβ3 integrin levels. / Mittra, Erik; Goris, Michael L.; Iagaru, Andrei H.; Kardan, Arash; Burton, Lindee; Berganos, Rhona; Chang, Edwin; Liu, Shuanglong; Shen, Bin; Chin, Frederick T.; Chen, Xiaoyuan; Gambhir, Sanjiv S.

In: Radiology, Vol. 260, No. 1, 01.07.2011, p. 182-191.

Research output: Contribution to journalArticle

Mittra, E, Goris, ML, Iagaru, AH, Kardan, A, Burton, L, Berganos, R, Chang, E, Liu, S, Shen, B, Chin, FT, Chen, X & Gambhir, SS 2011, 'Pilot pharmacokinetic and dosimetric studies of18F-FPPRGD2: A PET radiopharmaceutical agent for imaging αvβ3 integrin levels', Radiology, vol. 260, no. 1, pp. 182-191. https://doi.org/10.1148/radiol.11101139
Mittra, Erik ; Goris, Michael L. ; Iagaru, Andrei H. ; Kardan, Arash ; Burton, Lindee ; Berganos, Rhona ; Chang, Edwin ; Liu, Shuanglong ; Shen, Bin ; Chin, Frederick T. ; Chen, Xiaoyuan ; Gambhir, Sanjiv S. / Pilot pharmacokinetic and dosimetric studies of18F-FPPRGD2 : A PET radiopharmaceutical agent for imaging αvβ3 integrin levels. In: Radiology. 2011 ; Vol. 260, No. 1. pp. 182-191.
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abstract = "Purpose: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 (18F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine- aspartic acid (RGD) peptide sequence and targets αvβ 3 integrin, in the first volunteers imaged with this tracer. Materials and Methods: The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/μmol ± 714 [44.4 GBq/μmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistri bution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests. Results: The administration of 18F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/ mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of 18F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26{\%} ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096). Conclusion: 18F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients - especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.",
author = "Erik Mittra and Goris, {Michael L.} and Iagaru, {Andrei H.} and Arash Kardan and Lindee Burton and Rhona Berganos and Edwin Chang and Shuanglong Liu and Bin Shen and Chin, {Frederick T.} and Xiaoyuan Chen and Gambhir, {Sanjiv S.}",
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pages = "182--191",
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TY - JOUR

T1 - Pilot pharmacokinetic and dosimetric studies of18F-FPPRGD2

T2 - A PET radiopharmaceutical agent for imaging αvβ3 integrin levels

AU - Mittra, Erik

AU - Goris, Michael L.

AU - Iagaru, Andrei H.

AU - Kardan, Arash

AU - Burton, Lindee

AU - Berganos, Rhona

AU - Chang, Edwin

AU - Liu, Shuanglong

AU - Shen, Bin

AU - Chin, Frederick T.

AU - Chen, Xiaoyuan

AU - Gambhir, Sanjiv S.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - Purpose: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 (18F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine- aspartic acid (RGD) peptide sequence and targets αvβ 3 integrin, in the first volunteers imaged with this tracer. Materials and Methods: The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/μmol ± 714 [44.4 GBq/μmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistri bution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests. Results: The administration of 18F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/ mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of 18F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096). Conclusion: 18F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients - especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.

AB - Purpose: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 (18F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine- aspartic acid (RGD) peptide sequence and targets αvβ 3 integrin, in the first volunteers imaged with this tracer. Materials and Methods: The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/μmol ± 714 [44.4 GBq/μmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistri bution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests. Results: The administration of 18F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/ mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of 18F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096). Conclusion: 18F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients - especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.

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