pediatric nuclear medicine in 2003

Pediatric Nuclear Medicinein 2003

Michael J. Gelfand M.D.Cincinnati Children’s Hospital

Cincinnati, OH

Immediate Past-President ,Society of Nuclear Medicine

on behalf of the Society of Nuclear Medicine

Pediatric Nuclear Medicine

• Pediatric nuclear medicine is alive and well, and growing


Children’s Hospitals

Nuclear medicine procedure volumes in 2003

• Boston 8061

• Philadelphia 6539

• Cincinnati 4780


• The distribution of studies is quite different from adult nuclear medicine and varies from hospital to hospital

• What studies are being performed?

tumor 8%GI 6%

other 5%

bone 23%

GU 55%

Pediatric Nuclear Medicine at CCH

GU cases include:

• Cystography (Tc-99m-DTPA) 32%

• Other Tc-99m-DTPA renal 14%

• Tc-99m-DMSA renal 3.5%

• Tc-99m-MAG3 renal 5.5%


Tumor cases (8.2% of total ) include:• I-123-MIBG approx 2.4%• F-18-FDG PET 2.3%“Other” cases include:• Lung 2.2%• Brain perfusion and CSF 1.0%• Thyroid and endocrine 1.3%• Heart 0.4%



• At Cincinnati Children’s Hospital, we have experienced continued growth in Nuclear Medicine volumes, but at a somewhat slower rate than the total number of imaging examinations.


• Pediatric Nuclear Medicine is growing!• Boston and Philadelphia also report increasing

volumes• Pediatric Nuclear Medicine case volumes are

dependent on having an imaging physician who is interested in Pediatric Nuclear Medicine

• If the staff imaging physicians in a hospital are disinterested or believe that nuclear medicine is likely to disappear, nuclear medicine volumes will decline!


Myocardial perfusion imaging

Procedure volumes in 2002, 2003 –

Over 4000 per year in USA [2002]

• Boston approx 100 [2003]

• Philadelphia 224 [2003]


Myocardial perfusion imaging in pediatrics

Kawasaki’s disease[Paridon et al, J Amer Coll Cardiol 1995; 25:1425-1427].

46 patients, myocardial perfusion defects werepresent by Tc-99m-sestamibi• In 37% of 27 with normal coronary arteries by

angiography• In 63% of 11 with resolved aneurysms• In 100% of 8 with aneurysms



with Tc-99m-labeled radiopharmaceuticals

• Shorter t1/2 and lower absorbed radiation dose than Tl-201

• Better image quality than Tl-201

• Flexible timing of image acquisition

• Can obtain a gated wall motion study



After the arterial switch procedure for transpositionof the great vessels

[Weindling SN, etal. J Am Coll Cardiol 1994; 23:424-433].Myocardial perfusion defects were present on Tc-99m-sestamibi imaging• In 96% of 23 children, 4.2-7.9 years after

surgery• Defects were present at both rest and stress


• Radiation exposure from diagnostic pediatric nuclear medicine procedures is acceptable

• Comparisons between different radiographic procedures, and between radiographic procedures and nuclear medicine procedures, is accomplished by use of effective dose (ED) calculations

Effective Dose — How to Compare Apples and Oranges

• Effective dose (ED), therefore, is defined as: ED = Σ WTHT

T

where WT is weighting factor for tissue T and HT is the calculated dose for tissue T

Tumor Imaging

ED (rem)

CT of the chest, abdomen and pelvis(low dose technique) 0.6

Ga-67 (0.100 mCi/kg) 1.8 -2.5I-123-MIBG (0.140 mCi/kg) 0.26-0.29F-18-FDG (0.140 mCi/kg) 0.50-0.86

Ware DE, Huda W, et al. Radiology 1999;210:645 -650. Stabin MG, Gelfand MJ. Q J Nucl Med 1998; 42:93-112.

Imaging for Infection ED (rem)

CT of the chest, abdomen and pelvis 0.6Ga-67 (0.040 mCi/kg) 0.72-1.00Tc-99m-WBC (0.215 mCi/kg) 0.60-0.73In-111-WBC (0.070 mCi/kg) 0.57-0.75Renal onlyCT of the abdomen and pelvis 0.4CT limited to the kidney region 0.25Tc-99m-DMSA (0.033 mCi/kg) 0.05-0.11Ware DE, Huda W, et al. Radiology 1999;210:645 -650.

Stabin MG, Gelfand MJ. Q J Nucl Med 1998; 42:93-112.

Other Nuclear Medicine Studies ED (rem)

Heart-LungTc-99m-MAA (0.050 mCi/kg) 0.10-0.17Tc-99m-sestamibi (0.200 mCi/kg) 0.49-0.69Tl-201 (0.055 mCi/kg) 3.0 -6.1

Vesicoureteral refluxVoiding cystourethrogram 0.010-0.035Direct nuclear cystogram 0.002Schultz FW, et al. Br J Radiol 1999: 72:763-772.Hernandez RJ, Goodsitt MM. AJR Am J Roentgenol. 1996; 167:1247-53.Stabin MG, Gelfand MJ. Q J Nucl Med 1998; 42:93-112.

Other Nuclear Medicine Studies

ED (rem)BoneTc-99m-MDP (0.215 mCi/kg) 0.21-0.26

BrainTc-99m-ECD (0.285 mCi/kg) 0.28-0.67Tc-99m-HMPAO (0.285 mCi/kg) 0.59-0.81F-18-FDG (0.100 mCi/kg) 0.36-0.6

RenalTc-99m-MAG3 (0.070 mCi/kg) 0.02-0.07Tc-99m-DTPA (0.050 mCi/kg) 0.03-0.09Stabin MG, Gelfand MJ. Q J Nucl Med 1998; 42:93-112.


• Why we need implementation of the Best Pharmaceuticals for Children Act --

All use of radiopharmaceuticals in patients under age 18 years continues to be off-label

An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

21CFR361.1 (b) (3) (i) states with reference to studies performed under approval by a Radioactive Drug Research Committee:

“Under no circumstances may the radiation dose to an adult research subject from a single study or cumulatively from a number of studies conducted within 1 year be generally recognized as safe if such dose exceeds the following:”


21CFR361.1 (b) (3) (i) Whole body, active blood forming organs,

lens of eye and gonads

single dose 3 rem

annual and total dose commitment 5 rem

Other organs

single dose 5 rem

annual and total dose commitment 15 rem


21CFR361.1(b) (3) (ii) states:“For a research patient under 18 year of age at his

last birthday, the radiation dose shall not exceed 10% of that set forth in paragraph (b) (3) (i).”


The pediatric limits, therefore, become:Whole body, active blood forming organs,

lens of eye and gonads

single dose 0.3 rem

annual and total dose commitment 0.5 rem

Other organs

single dose 0.5 rem

annual and total dose commitment 1.5 rem


• This greatly limits the ability to study new PET agents in children with cancer or other life threatening diseases.

• Absorbed radiation doses for most PET radiopharmaceuticals far exceed 0.3 rem whole body and 0.5 rem to any organ

• The limits may also pose a problem for studies using SPECT radiopharmaceuticals


[F-18] 2-fluoro-2-deoxyglucose

• For 9.8 mCi in a 70 kg adultED 0.88 rem bladder wall 6.8 rem

• For 4.5 mCi in a 10 year oldED 0.64 rem bladder wall 3.6 rem

• For 2.6 mCi in a 5 year oldED 0.56 rem bladder wall 3.0 rem

Stabin MG, Gelfand MJ. Q J Nucl Med 1998: 42:93-112.


[F-18] fluorocholine -- for 7.7 mCi in a 70 kg adultED 1.0 rem kidney 2.46 rem

DeGrado TR, et al. J Nucl Med 2002; 43:509.

[F-18] fluorodopa -- for 9.0 mCi in a 70 kg adultED 0.60 rem bladder wall 5.1 rem

Dhawan V, et al. J Nucl Med 1996; 37:1850-1852.

[F-18] fluorothymidine – for 5.0 mCi in a 70 kg adultEDE 1.0 rem bladder wall 3.26 rem

Vesselle H, et al. N Nucl Med 2003;1482-1488.

C-11 methionine – for 20 mCi in a 70 kg adultED 0.33 rem bladder wall 1.73 rem

Deloar HN, et al. Eur J Nucl Med Mol Imag 1998; 25:629-633.


• What about using faster PET cameras?

Even with a 50% reduction in administered activity, absorbed radiation doses exceed the limits.

• Why not reduce the administered activity another 50% and double the imaging time?

Even with an additional 50% reduction in administered activity, absorbed radiation doses still exceed the limits.


• Effective dose (ED) takes into account the risk associated with radiation dose to each organ and tissue, but the RDRC regulations set an arbitrary standard that no target organ dose shall exceed the whole body dose by more 67%.

• Whole body absorbed radiation dose is no longer widely used.

• The target organ dose for most radiopharmaceuticals is usually more than 67% above the whole body dose or the ED.


• With the current RDRC regulations, molecular imaging technology will not be readily available for the study of pediatric cancer or other life threatening diseases.

• With the current RDRC regulations, evaluation of new molecular imaging methods in pediatric cancer, or other life threatening diseases, will be significantly delayed.

• An up to date standard should be developed, based on effective dose, with limits that permit the study of children with cancer or other life threatening diseases.

Pediatric Nuclear Medicine Research

• Children and adults may differ in the pharmacokinetics of drugs

• Pediatric disease processes are different from adult disease processes

• Pediatric data from adequate and well controlled clinical trials are better than extrapolated adult data

pediatric nuclear medicine in 2003

Documents

nuclear medicine volumes

society of nuclear medicine

adult nuclear medicine

direct nuclear cystogram

renal tc

brain tc

cystography tc

sestamibi imaging