Inflammation / Infection Detection

J. Anthony Parker, MD PhD

Case

Radiopharmaceuticals

Agents

Iron analogs

Ga-67 citrate
In-111 chloride (not FDA approved)

White blood cells

In-111 oxine labeled autologous white blood cells
Tc-99m HMPAO labeled autologous white blood cells

Non-specific IgG (In-111 or Tc-99m) (not FDA approved)
Peptides (not FDA approved)

Definsins, e.g. human neutrophil peptide, HNP-1
Tc-99m Neutrophil Elastase Inhibitor

Polyethyleneglycol (PEG) stabalized liposomes
Antibodies (FDA approval pending)

To WBCs (Leutech - Tc99m anti-CD15 Antibody)

Agent of Choice

Depends upon indication
May depend upon poly vs. non-poly infection
May depend upon site
The right answer is left as an exercise

Pitfalls

Gallium

Iron overload
Recent chemotherapy

White Blood Cells

Neutropenia
Injecting the wrong patient

Technique

Ga-67 Citrate

Images at 1-3 days
Follow-up as necessary
Three peaks: 92, 182, & 300 keV
Medium energy collimator
Whole body
SPECT as appropriate - photon limited

In-111 Oxine labeled White Blood Cells

8-hydroxyquinoline
Image at 1 day

Blood clearance T1/2 is 7.5h
Early lung margination

Two peaks: 247 & 173 keV
Medium energy collimator
Whole body
SPECT as appropriate - photon limited
Consider sulfur colloid dual isotope scan for osteomyelitis

Tc-99m Exametazime (HMPAO) labeled White Blood Cells

Hexamethylpropylene amine oxime
Image at 4 hours and 1 day

Blood clearance T1/2 is 4h
Early lung margination
Bowel activity normally seen

Peaks: 140 keV
Low energy collimator
Whole body
SPECT as appropriate

Tc-99m Leutech Anti-CD15 Antibody

Murine anti-CD15 IgM monoclonal antibody
Kit preparation
75-125 ug
Dynamic over 90 minutes
Peaks: 140 keV
Low energy collimator
Whole body
SPECT as appropriate

Non-specific IgG

Blood T1/2 13h and 72h

Dosimetry

Radiopharmaceutical	Administered Activity		Effective Dose
Radiopharmaceutical	MBq	mCi	cSv
In-111 IgG	75	2	1.5
Tc-99m IgG	370	10	0.3
In-111 WBCs	25	0.7	1.5
Tc-99m WBCs	370	10	0.6
Ga-67 citrate	220	6	2.7
Tc99m Leutech	370-740	5-10	TBA

Mechanisms of Uptake

Ga-67 Citrate

Leaky vessels
Iron analog
Iron is cofactor in H2O2 production -> superoxide
On Transferrin in blood
On lactoferrin in cells / excretions
Lactoferrin in inflammation

In-111 Chloride

Transferin receptors
Probably the same as Ga-67 Citrate

In-111 Oxine labeled White Blood Cells

Polynomial leukocytes only

Tc-99m HMPAO labeled White Blood Cells

Polynomial leukocytes only

Peptides

Inflammation / infection analogous

Antibodies

CD15: leukocytes
Labels both circulating and already fixed WBCs

Indications

"FUO"
Osteomyelitis
Prosthetic infection
Inflamitory bowel disease
Vascular graft
Appendicitis (Leutech)

Acute Appendicitis

Tc-99m WBC

Tc-99m Leutech

N = 58

N = 49

	D+	D-
T+	27	8
T-	0	23

	D+	D-
T+	26	4
T-	0	19

Sens = 100%
Spec = 74%

Sens = 100%
Spec = 83%

t(positive) = 72 min
t(nuke->Sx) = 6.8 h

t(positive) = 42 min
t(nuke->Sx) = 5.5 h

Acute Appendicitis

N = 200 (including prior table)
123F / 79M
5-86 y

	D+	D-
T+	53	19*
T-	6	122

*5/19 other infection

Sens = 90%
Spec = 87%

t < 30 min for 84% of poitives

Interpretation

Normal Sites of Uptake

Ga-67 Citrate

Liver
Bones
Bone marrow
Lachrymal glands
Spleen - variable, should generally be less than liver
GI tract - route of excretion
Scrotal region

In-111 Oxine labeled White Blood Cells

Liver
Spleen - intense
Marrow - faint

Tc-99m HMPAO labeled White Blood Cells

Liver
Spleen - intense
Marrow - faint
Gall bladder - a route of excretion
GI tract - on 1 day images
WBC lung margination on early images

Tc-99m Leutech

Abnormalities

Focal infection
Diffuse organ or cavity
Inhomogeneity of normal structure - versus other focal process

Gallium lung uptake

Diffuse

Intense

PCP
Chemotherapy - Bleomycin as prototype
Lymphangiogram

Faint

PCP
CMV
Other viral
Lots of stuff

Regional

Pneumonia

Focal

Lymphoma - especially hilar
MAI - especially mediastinal
Lung CA - especially parenchyma
Any cancer

Normal

Normal
Kaposis (Tl-201 is positive)

Pitfalls

Spleen on Gallium scan
Gastritis on Gallium scan
Cancer on Gallium scan
GI tract on Tc-99m HMPAO WBC
GI tract on WBC with respiratory infection
Lung on early WBC

Cases

J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu