# Presentation: 049864

## Pediatric Nuclear Medicinein 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

## Pediatric Nuclear Medicine

- Children’s Hospitals
- Nuclear medicine procedure volumes in 2003
- Boston			8061
- Philadelphia		6539
- Cincinnati		4780

## Pediatric Nuclear Medicine

- The distribution of studies is quite different from adult nuclear medicine and varies from hospital to hospital
- What studies are being performed?

## 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%

- Cystography (Tc-99m-DTPA)	32%
- Other Tc-99m-DTPA renal		14%
- Tc-99m-DMSA renal			3.5%
- Tc-99m-MAG3 renal			5.5%

- Pediatric Nuclear Medicine at CCH

## 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%

- 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%

- Pediatric Nuclear Medicine at CCH

## Pediatric Nuclear Medicine

- 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.

## Slide 9

## Pediatric Nuclear Medicine

- 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!

## Pediatric Nuclear Medicine

- Myocardial perfusion imaging
- Procedure volumes in 2002, 2003 –
- 	Over 4000 per year in USA [2002]
- Boston			approx 100 [2003]
- Philadelphia		224 [2003]

## Pediatric Nuclear Medicine

- Myocardial perfusion imaging in pediatrics
- Kawasaki’s disease
- 	[Paridon et al, J Amer Coll Cardiol 1995; 25:1425-1427].
- 46 patients, myocardial perfusion defects were
- present 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

## Pediatric Nuclear Medicine

- Myocardial perfusion imaging in pediatrics
- 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

## Pediatric Nuclear Medicine

- Myocardial perfusion imaging in pediatrics
- After the arterial switch procedure for transposition
- of 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

## Pediatric Nuclear Medicine

- 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 (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

- 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

## 							    	ED (rem)
CT of the chest, abdomen and pelvis
	(low dose technique)				0.6
Ga-67 (0.100 mCi/kg)				1.8  -2.5
I-123-MIBG (0.140 mCi/kg)			0.26-0.29
F-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. 

**	****	****	****	****	****	****	****    ****	**ED (rem)
- CT of the chest, abdomen and pelvis
- 	(low dose technique)				0.6
- Ga-67 (0.100 mCi/kg)				1.8  -2.5
- I-123-MIBG (0.140 mCi/kg)			0.26-0.29
- F-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.

## 							    	ED (rem)
CT of the chest, abdomen and pelvis 		0.6
Ga-67 (0.040 mCi/kg)					0.72-1.00
Tc-99m-WBC (0.215 mCi/kg)				0.60-0.73
In-111-WBC (0.070 mCi/kg)				0.57-0.75
Renal only
CT of the abdomen and pelvis			0.4
CT limited to the kidney region			0.25
Tc-99m-DMSA (0.033 mCi/kg)			0.05-0.11
Ware DE, Huda W, et al.   Radiology 1999;210:645 -650. 
Stabin MG, Gelfand MJ.  Q J Nucl Med 1998; 42:93-112. 

**	****	****	****	****	****	****	****    ****	**ED (rem)
- CT of the chest, abdomen and pelvis 		0.6
- Ga-67 (0.040 mCi/kg)					0.72-1.00
- Tc-99m-WBC (0.215 mCi/kg)				0.60-0.73
- In-111-WBC (0.070 mCi/kg)				0.57-0.75
- Renal only
- CT of the abdomen and pelvis			0.4
- CT limited to the kidney region			0.25
- Tc-99m-DMSA (0.033 mCi/kg)			0.05-0.11
- Ware DE, Huda W, et al.   *Radiology* 1999;210:645 -650.
- Stabin MG, Gelfand MJ.  *Q J Nucl Med* 1998; 42:93-112.

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

Vesicoureteral reflux
Voiding cystourethrogram			0.010-0.035
Direct nuclear cystogram 			0.002	

Schultz 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. 	

**	****	****	****	****	****	****    ****	**ED (rem)
- _Heart-Lung_
- Tc-99m-MAA (0.050 mCi/kg)		0.10-0.17
- Tc-99m-sestamibi (0.200 mCi/kg)		0.49-0.69
- Tl-201 (0.055 mCi/kg)			3.0  -6.1
- _Vesicoureteral reflux_
- Voiding cystourethrogram			0.010-0.035
- Direct nuclear cystogram 			0.002
- Schultz 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. **	**
-  **	**

## 						    	ED (rem)
Bone
Tc-99m-MDP (0.215 mCi/kg)			0.21-0.26

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

Renal
Tc-99m-MAG3 (0.070 mCi/kg)			0.02-0.07
Tc-99m-DTPA (0.050 mCi/kg)			0.03-0.09

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

**	****	****	****	****	****	****    ****	**ED (rem)
- _Bone_
- Tc-99m-MDP (0.215 mCi/kg)			0.21-0.26
- _Brain_
- Tc-99m-ECD (0.285 mCi/kg)			0.28-0.67
- Tc-99m-HMPAO (0.285 mCi/kg)		0.59-0.81
- F-18-FDG (0.100 mCi/kg)			0.36-0.6
- _Renal_
- Tc-99m-MAG3 (0.070 mCi/kg)			0.02-0.07
- Tc-99m-DTPA (0.050 mCi/kg)			0.03-0.09
- Stabin MG, Gelfand MJ.  *Q J Nucl Med* 1998; 42:93-112. **	**

## Pediatric Nuclear Medicine

- 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:”

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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).”

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- [F-18] 2-fluoro-2-deoxyglucose
- For 9.8 mCi in a 70 kg adult
- 	ED	0.88 rem		bladder wall 6.8 rem
- For 4.5 mCi in a 10 year old
- 	ED	0.64 rem		bladder wall 3.6 rem
- For 2.6 mCi in a 5 year old
- 	ED	0.56 rem		bladder wall 3.0 rem
- Stabin MG, Gelfand MJ.  Q J Nucl Med 1998: 42:93-112.

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- [F-18] fluorocholine -- for 7.7 mCi in a 70 kg adult
- 	ED	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 adult
- 	ED	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 adult
- 	EDE  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 adult
- 	ED	0.33 rem		bladder wall 1.73 rem
- Deloar HN, et al.  Eur J Nucl Med Mol Imag 1998; 25:629-633.

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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.

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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.

## An Important Regulatory Limitation on Pediatric Nuclear Medicine Research

- 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