Journal of Surgical Oncology 2008;97:369–371

GUEST EDITORIAL

Use of PET Probe in Surgical Oncology

MANUEL MOLINA, MD AND ELI AVISAR, MD*Department of Surgery/Surgical Oncology, Miller School of Medicine, University of Miami, Florida

INTRODUCTION

Since the introduction of PET scan using 18FDG in 1993 for the

localization of colon metastasis, the field of nuclear medicine and

oncology has made a tremendous advance in the detection of occult

metastasis.

This technology is based on the principles of increase glucose

consumption by the tumor cells and the ability to detect the photon

produced by the breakdown of 18FDG inside the cancer cells.

Currently, the applications of this technology have broaden to a large

number of tumors such as melanoma, lung cancer, GIST, lymphoma,

head and neck tumors, thyroid cancer, colon cancer, breast cancer,

stomach cancer, pancreatic cancer, esophageal cancer, and others in

order to assess the extent of the tumor or in follow-up for possible

cancer recurrence. Recently, PET scan has been used also to monitor

tumor response to therapy. Excellent sensitivity and good specificity

have been reported.

In the early 1990’s, the use of intraoperative radioactive detectors

started spreading quickly with the development of the sentinel lymph

node concept using 99mTc sulfur colloid in melanoma and eventually in

breast cancer. The next natural step was to devise an intraoperative

detector for 18FDG avid lesions identified by PET scans. Unfortu-

nately, the commonly available gamma detectors used for sentinel node

biopsies were not suitable for the task because of the lack of shielding

for high-energy gamma rays emitted by F-18 (511 keV), and small size

of their detectors that was optimized for low-energy gamma rays of Tc-

99m (140 keV). In the last 10 years, the development of high-energy

gamma probes with excellent sensitivity for 18FDG avid lesions

brought to the clinician a new intraoperative tool.

The aim of this article is to review the technology, applications,

safety, and future applications of PET probe-guided surgery.

TECHNOLOGY

The 18FDG molecules enter the tumor cells using facilitative

glucose transporters (glucose transporter-1) and undergo phosphoryla-

tion to PDG-6 by hexokinase which accumulates in the tumor

cells secondary to a slow dephosphorylation. The 18F molecule is

released and its radioactive decay causes the ejection of a positron from

the nucleus. After traveling a couple of millimeters, the positron

collides with an electron resulting in two 511 keV photons traveling at

1808 from each other. The detection of these photons is the base of the

PET scan and high-energy gamma probes. The half-life of 18 FDG is

110 min. The probe threshold is set at 490 keV and has a window of

20 keV, allowing the accurate detection of the 511 keV gamma ray

photons.

For the performance of PET probe-guided surgery, the patient is

injected with 5–15 mCi FDG 2–4 hr prior to surgery. Since the

technique is based on the metabolism of glucose, a strict monitoring of

glucose levels is required throughout the injection and surgery process.

No glucose containing IV fluids are given previous or during surgery

and strict glycemic control of diabetic patients is required

(glucose< 140). A minimum target to background ratio (TBR) of

1.5:1 is necessary for accurate detection of 18FDG avid lesions. For that

reason, at least 60 min of quiet time should be allowed after injection.

The TBR, however, improves overtime with the best results obtained

3–4 hr after injection. This occurs because the FDG metabolism and

clearance occur faster in normal tissue than in tumor tissue resulting in

TBR improvement with time. Boerner et al. [1] found an 83% lesion

detectability 1.5 hr after injection compared to 93% after 3 hr. The

TBR is affected close to high glycolytic activity organs such as the

brain, heart, kidney, and bladder, limiting the detection of lesions in

those areas. Recent studies demonstrated that lesions with SUV> 3

and larger than 0.8 cm were easily detectable with intraoperative high-

energy gamma probe use. The detection of these lesions is also

influenced by the glycolytic activity of the tumor and the mass of

viable tumor cells which may be variable within the same tumor and

between different tumors.

CLINICAL APPLICATION

With the wide spread of PET scan use for cancer staging, the

surgical oncologist is often consulted to consider the biopsy or

resection of FDG avid lesions. The surgical approach, however, can be

significantly complicated by a hostile surgical field with adhesions

from previous surgery, radiation changes, or chemotherapy-related

alterations. Sometimes, the FDG avid lesion is an occult finding

identified only by PET scan and none of the other available imaging

modalities. In those cases, PET probe guidance can be a useful

intraoperative adjunct focusing the surgical effort toward the FDG

avid lesion, reducing the operative time and preventing unnecessary

dissection and damage to surrounding structures.

The possible false positive findings on PET scans warrant a word of

caution before embarking in PET probe-guided surgery especially

when dealing with FDG avid lesions without other correlative imaging

findings. Usually, persistence on two subsequent PET scans and an

increasing SUV value should be required before explorative surgery. In

addition, when dealing with resection of metastatic lesions in an effort

to achieve a ‘‘no evidence of disease’’ status the same general oncology

Authors have a conflict of interest: Travel support for a conference—Intramedical Imaging LLC.

*Correspondence to: Eli Avisar, MD, UM/SCCC, 1475 NW 12th Avenue,Room 3550, Miami, FL 33136. Fax: 305 243 4907.E-mail: eavisar@med.miami.edu

Received 31 October 2007; Accepted 2 November 2007

DOI 10.1002/jso.20947

Published online 27 December 2007 in Wiley InterScience(www.interscience.wiley.com).

� 2007 Wiley-Liss, Inc.

principles applied for metastatic nodules identified with other imaging

modalities should be used.

The intraoperative use of PET probes for resection of a variety of

solid organ metastatic lesions have been described.

For breast cancer, reoperation in a difficult axilla with an increased

risk for injury to the long thoracic or thoracodorsal nerves or resection

of metastatic lymph nodes in the previously operated and radiated

interpectoral space have been facilitated with FDG guidance.

Resection of recurrent and metastatic melanoma to lymph nodes in

the groin, pelvis, retroperitoneum, and neck was also facilitated with

the guidance of a high-energy gamma probe, improving the detection

and removal rate and enabling the intraoperative identification and

removal of additional lesions. Franc et al. demonstrated a sensitivity of

89% with a specificity of 100%.

Localization of metastatic lymph nodes in head and neck tumors has

become an area of special interest since the guidance provided by the

PET probes can avoid damage to important nerves and vital organs

especially during difficult dissections in reoperative and radiated fields.

This particular topic was addressed by Meller et al. [2] comparing

the accuracy of PET scan, US and PET probes for the localization of

metastatic lymph nodes in head and neck malignancies. PET and US

probes demonstrated a 95% sensitivity each but the PET probe had a

60% specificity compared to 40% specificity for ultrasound. This study

showed the superiority of this technique in the head and neck area.

Curtet et al. described the used of PET probes for the detection of

Iodine scan negative recurrent thyroid tumors with 100% accuracy in

seven patients.

Another important application is in the detection of recurrent colon

cancer. Sarikaya et al. studied the accuracy of high-energy gamma

probes in the detection of recurrent colon cancer. The accuracy was

81% with tumors<1 cm and with a mean SUVof 8.27 for true positive

lesions and 3.65 for false negative lesions. This study included

21 patients with recurrent lesions in the rectum, peritoneum, abdominal

wall, portahepatis, retroperitoneum, pelvis, lung, and liver. The CEA

level was elevated only on 11 patients [3].

Resection of recurrent gastric cancer is especially difficult in

patients undergoing total gastrectomy and radical lymphadenectomy

where the visualization and palpation of the tumor can be compromis-

ed by scarring increasing the chance of damage to adjacent vital

organs.

Recent reports of the use of laparoscopic resection of occult

metastasis in patients with ovarian cancer using a laparoscopic high-

energy gamma probe by Barranger et al. shows the application of the

radio-guided surgery to the field of laparoscopy. This technique

combines the accuracy of the PET probes with the advantages of

the minimally invasive surgery. This is an area that can be potentially

applicable to remove recurrence, occult lesions, or metastasis in areas

accessible by minimally invasive surgery: thorax, mediatinum, abdo-

men, pelvis, retroperitoneum, abdominal wall [4].

PET probes can also be used for the diagnosis, staging, or restaging

of lymphomas in difficult surgical areas. Typical examples include

biopsy of FDG avid lymph nodes in the retroperitoneum or for accurate

identification of an avid lymph node among enlarged but non-avid

lymph nodes such as after lymphoma treatment.

SAFETY

Unpublished data from Heckathorne et al. investigated the radiation

exposure to the surgical team and nursing staff. Their results

demonstrated that for surgeries performed between 1 and 3 hr after

injection of 10 mCi (370MBq) of 18FDG the effective radiation dose to

the surgeon is 59 mSv (5.9 mrem) and to the nursing staff 22 mSv(2.2 mrem). This will allow the surgeon to perform 800 procedures

per year without exceeding the occupational dose limit of 50 mSv.

Piert et al. also measured the effective radiation dose to the surgeons

and anesthesiologist during radio-guided surgery. After the adminis-

tration of 36–110 MBq of 18FDG to two patients, the surgeons

received a radiation dose of 2.5 to 8.6 mSv/hr and the anesthesiologist

0.8 mSv/hr.Although the radiation exposure to the surgical team is higher than

the one seen with 99Tc used for sentinel lymph node biopsy, it is still

very low compared with the occupational dose limit, making this

technique safe enough to continue developing.

FUTURE APPLICATIONS

The use of F-18-labeled deoxyglucose for the detection of cancer

cells makes possible the use of a different type of radiation detection

probe that is selectively sensitive to the positrons. Since positrons have

a range of 2 mm in tissue, this new type of probe called beta probe, can

locate small tumor deposits [5]. This probe is exclusively sensitive to

short range positrons and highly sensitive to minute amounts of cancer

cells that can be located millimeters from the surgical margin. This can

be applied to the detection of negative margins at the time of surgery

without the need for frozen section and reduce the reoperation rate for

positive margins. The beta probe also has the advantage of overcoming

one of the limitations of gamma probes which is the need to

differentiate between the signal and the background obscuring the

ability to localize small tumors with low TBR. Since the beta rays have

a very short depth of penetration in the tissue (1 mm), the beta probe

ability to detect radioactivity is not affected by the background gamma

radiation from normal tissues. Although beta probes were described a

few years before high-energy gamma probes, the clinical use of this

probe has not been established yet and preliminary clinical studies are

on their way using beta probes.

Intraoperative Beta-Ray imaging uses the same principle as the beta

probe and is able to create a real-time image using a hand-held camera.

The beta camera can provide an image of FDG activity near the surface

of the surgical field or the surgical specimen potentially assisting in the

evaluation of the resection margin.

CONCLUSION

The use of high-energy gamma probes for the detection of gamma

photons emitted by the decay of 18FDG is gaining an important role in

the reoperative surgical oncology for metastasectomy or recurrent

tumors in scarred surgical field. The ability to guide the surgeon to a

specific area in order to remove tumors not easily seen or palpable with

excellent accuracy and the decreased risk for adjacent organ damage

along with reduction in the operative time is a novel concept that has

been already tested and confirmed by different authors. The application

of this technology to tumors in the head and neck area, lymphoma,

breast cancer, colon cancer, and others neoplasms and the ability to

remove all detectable cancer deposits is an important factor that can

potentially impact the survival of patients with resectable metastatic or

recurrent disease. New technology using beta rays probes and cameras

can potentially detect much smaller tumor deposits within a few

millimeters from the detector. Additional clinical experience will

better define the usefulness and applications of this developing

technology. The preliminary results seem to indicate that PET probes

are here to stay.

REFERENCES

1. Boerner AR, Weckesser M, Herzog H, et al.: Optimal scan time forfluorine-18 fluorodeoxyglucose positron emission tomography inbreast cancer. Eur J Nucl Med 1999;26:226–230.

Journal of Surgical Oncology

370 Molina and Avisar

2. Meller B, Sommer K, Gerl J, et al.: High energy probe for detectinglymph node metastasis with 18F-FDG in patients with head andneck cancer. Nuklearmedizin 2006;45:153–159.

3. Sarikaya I, Povoski S, Al-Saif OH, et al.: Combined use ofpreoperative 18F FDG-PET imaging and intraoperative gammaprobe detection for accurate assessment of tumor recurrencein patients with colorectal cancer. World J Surg Oncol 2007;5:80.

4. Barranger E, Kerrou K, Petegnief Y, et al.: Laparoscopic resectionof occult metastasis using the combination of FDG-positronemission tomography/computed tomography image fusion withintraoperative probe guidance in a woman with recurrent ovariancancer. Gynecol Oncol 2005;96:241–244.

5. Daghighian F, Mazziotta JC, Hoffman EJ, et al.: Intraoperative betaprobe: A device for detecting tissue labeled with positron orelectron emitting during surgery. Med Phys 1994;21:153–157.

Journal of Surgical Oncology

Guest Editorial 371