Vol. 17, No. 4, 2003
Annals of Nuclear Medicine Vol. 17, No. 4, 333–336, 2003
Received December 2, 2002, revision accepted March 18,
For reprint contact: Toshiki Shiozaki, M.D., Ph.D., Depart-
ment of Radiology, Kyoto City Hospital, 1–2, Higashitakada-
cho, Mibu, Nakagyo-ku, Kyoto 604–8845, JAPAN.
HEPATOCELLULAR CARCINOMA (HCC) is one of the most
lethal and prevalent cancers in the world. Because therapy
for HCC has improved, the prognosis has improved and
the rate of extrahepatic metastasis detection has increased.
Hasegawa et al. first reported that 99mTc-Sn-N-pyridoxy-
5-methyltryptophan (99mTc-PMT) is useful for detecting
the metastases of HCC.1 Since then 99mTc-PMT has been
used in the metastatic work-up for HCC in tissues such as
bone,2 lung,3 colon,4 hypopharynx,5 and orbit.6 To our
knowledge, no report has described the accumulation of
99mTc-PMT in renal metastases of HCC on scintigraphy.
We describe a case of renal metastasis from HCC in which
99mTc-PMT scintigraphy was useful for tissue character-
ization of the lesion.
A 56-year-old man developed a palpable tumor in the left
upper abdomen in 1996. Computed tomography (CT)
revealed a tumor in the left lobe of the liver. Antibody tests
to hepatitis C virus and surface antigen of hepatitis B were
negative. A left lobectomy of the liver was done, and the
tumor was diagnosed histologically as Edmondson type
II–III HCC. In 1998 and 1999, the patient underwent two
partial lung lobectomies for HCC metastases.
In April 2002, when the patient was 62 years old, he
developed left flank pain and underwent an abdominal CT
that showed a left renal tumor (Fig. 1). On MRI, the tumor
was hypointense compared with normal kidney tissue
on contrast T1-weighted image (Fig. 2). 99mTc-dimer-
captosuccinic acid scintigraphy revealed a space-occupy-
ing lesion in the left kidney as a cold area (Fig. 3).
Because the AFP level was elevated, renal metastasis
of HCC was suspected and 99mTc-PMT scintigraphy was
performed. Posterior abdominal images were obtained at
10, 20, 30, 40, and 50 min after intravenous injection of
185 MBq of 99mTc-PMT. 99mTc-PMT images showed an
accumulation in the tumor (Fig. 4).
Left nephrectomy was performed. A nodule was de-
tected in the cortex of the kidney. Renal medulla was
invaded by the tumor (Fig. 5-A). The location of the tumor
corresponded to that of the accumulation of 99mTc-PMT.
Light microscopy of hematoxylin-and-eosin-stained sec-
tions demonstrated a metastatic HCC tumor, Edmondson
type II–III (Fig. 5-B). The patient recovered uneventfully
and was discharged 1 month later.
HCC is one of the most common and fatal malignancies
in the world. Treatment methods for HCC have advanced
and now include such procedures as transcatheter arte-
rial embolization, percutaneous ethanol injection, and
Accumulation of 99mTc-PMT in renal metastasis of hepatocellular carcinoma
Toshiki SHIOZAKI,* Katsumi HAYAKAWA,* Masato TANIKAKE,* Tomoyuki OIDA,** Shuichi HIDA,**
Hiroshi YASUI,*** Yoji URATA,*** Akira TANAKA**** and Taisuke MORIMOTO****
Departments of *Radiology, **Urology, ***Pathology, and ****Surgery, Kyoto City Hospital
We describe here a case in which 99mTc-Sn-N-pyridoxy-5-methyltryptophan (99mTc-PMT) scintig-
raphy was useful in diagnosing renal metastasis of hepatocellular carcinoma (HCC). A 62-year-old
man who had undergone hepatectomy for HCC presented 6 years after initial diagnosis with
left flank pain and was found on CT and MRI to have a tumor in the left kidney. Hepatobiliary scin-
tigraphy using 99mTc-PMT was performed, and 99mTc-PMT accumulation was found in the tumor.
Nephrectomy was performed and metastasis of HCC was confirmed.
Key words: 99mTc-PMT, hepatocellular carcinoma, renal metastasis
Annals of Nuclear Medicine
Toshiki Shiozaki, Katsumi Hayakawa, Masato Tanikake, et al
Fig. 1 Contrast-enhanced CT scan showed a tumor in the cortex
and the medulla of the left kidney.
Fig. 2 Contrast-enhanced T1-weighted image showed a nodule
in the cortex of the left kidney. The medulla of the left kidney
was hypointense compared with normal kidney tissue.
Fig. 3 99mTc-dimercaptosuccinic acid scintigraphy from a
posterior view. A space-occupying lesion in the left kidney was
visualized as a cold area with 99mTc-dimercaptosuccinic acid.
Fig. 4 99mTc-PMT images from the posterior view at 10 (A), 20
(B), and 30 (C) min. A: 99mTc-PMT image from posterior view
at 10 min shows slightly increased uptake at the known tumor in
the left kidney (arrow). (The left lobe of the liver has been re-
sected.) B, C: 99mTc-PMT image from posterior view at 20 and
30 min still shows a slightly increased uptake at the known tumor
(arrow). The tracer excreted into the biliary system has flowed
to the stomach and third portion of the duodenum.
Vol. 17, No. 4, 2003
percutaneous radiofrequency tumor ablation. Because
therapy for HCC has improved, the prognosis has im-
proved and the rate of detection of extrahepatic me-
tastases has increased. Early initiation of therapy after
early detection is crucial to maintaining patients’ quality
Hepatobiliary scanning agents such as 99mTc-PMT
accumulate in the liver and are excreted into the biliary
system. Some cells of HCC retain the capability to incor-
porate these agents in a way similar to that of normal
hepatocytes. Accumulation of these agents in various
metastatic lesions has been reported.1–6
In our patient, we could not exclude primary tumors
such as renal cell carcinoma or transitional cell carcinoma
before 99mTc-PMT scintigraphy was done. This is be-
cause renal metastasis of HCC is often not found until
autopsy, and it is rare for this diagnosis to be confirmed
while a patient still alive. In a search of the literature we
found only 5 cases in which renal metastasis of HCC was
diagnosed in living patients.7–11 In Japan, at autopsy the
incidence of renal metastasis in patients with HCC has
been estimated at 3.8%.12 To our knowledge, this is the
first report of the usefulness of 99mTc-PMT in the diag-
nosis of renal metastasis of HCC.
Hasegawa et al. reported that the uptake of 99mTc-PMT
is significantly correlated with the degree of histologic
differentiation13 and with the prognosis of patients with
HCC.14 In their study, the probability of HCC showing
increased uptake of 99mTc-PMT was 105 times higher in
Fig. 5 A: Photograph of cut surface of the resected left kidney. A nodule
was detected in the cortex of the kidney. Renal medulla was invaded by the
tumor (arrowheads). The location and the shape of the tumor corresponded
to those of the accumulation of 99mTc-PMT. The location and the shape of
the tumor agreed with that of 99mTc-PMT images. B: Microphotograph of
resected kidney showing neoplastic growth of hepatocyte-like polygonal
epithelial cells with thick trabecular structure, separated by sinusoid-like
thin vascular stroma. These histopathological features are compatible with
those of hepatocellular carcinoma. (Hematoxylin-and-eosin-stained, 40 ×)
patients with Edmondson type I tumors than in those with
Edmondson type III. In our patient, the degree of 99mTc-
PMT uptake in the tumor was faint. This may be consis-
tent with Hasegawa’s results.
The limitations of the report include difficulty in distin-
guishing the accumulation of 99mTc-PMT in the tumor
from the urinary excretion of 99mTc-PMT. It was reported
that the urinary excretion of 99mTc-PMT was low,15 with
only 2% of the dose escaping through the kidneys at 2 hr
after injection.16 In our patient, the accumulation of 99mTc-
PMT corresponded to the location of the tumor in the
resected kidney; hence we believe that the accumulation
was due to a renal metastasis of HCC (Figs. 4, 5).
We suggest that 99mTc-PMT is useful for tissue charac-
terization of lesions that are thought to be renal metastases
1. Hasegawa Y, Nakano S, Ibuka K, Hashizume T, Sasaki Y,
Imaoka S, et al. Concentration of 99mTc-Sn-N-pyridoxyl-5-
methyltryptophan, a biliary agent, in distant metastases of
hepatomas. Eur J Nucl Med 1985; 10: 255–258.
2. Calvet X, Pons F, Bruix J, Bru C, Lomena F, Herranz R, et
al. Uptake of technetium-99m DISIDA uptake by bone
metastasis from a hepatoma. Clin Nucl Med 1988; 13: 280.
3. Archibeque F, Williamson MR, Rosenberg R, Eisenberg B,
Davis M, et al. Hepatoma: Tc-99m DISIDA uptake in
primary and metastatic lesions. Clin Nucl Med 1989; 14:
Annals of Nuclear Medicine Download full-text
Toshiki Shiozaki, Katsumi Hayakawa, Masato Tanikake, et al
4. Fukui H, Kashiwagi T, Shirai Y, Matsuda Y, Kawata S,
Nishimura T, et al. Metastasis of Hepatocellular Carcinoma
to the Colon Demonstrated by Tc-99m PMT Scintigraphy.
Clin Nucl Med 1993; 18: 512–515.
5. Hayase N, Fukumoto M, Yoshida D, Kariya S, Akagi N,
Kurohara A, et al. Extraosseous metastases of hepatocellu-
lar carcinoma detection and therapeutic assessment with
Tc-99m PMT SPECT. Clin Nucl Med 1999; 24: 326–329.
6. Hosokawa C, Kawabe J, Okamura T, Kamino T, Ikeda H,
Ochi H, et al. Usefulness of Tc-99m-PMT SPECT and F-
18-FDG in diagnosing Orbital Metastasis of Hepatocellular
Carcinoma. KAKU IGAKU (Jpn J Nucl Med) 1994; 31:
7. Yoshida H, Tsuji K, Sakurai Y, Katanuma A, Jong-Hon K,
Hayashi T, et al. A case of hepatocellular carcinoma with
renal metastasis 1 year and 3 months after hepatectomy.
Nippon Shokakibyo Gakkai Zasshi 2001; 98: 1283–1288.
8. Mezawa S, Homma H, Doi T, Takada K, Kukitsu T,
Kinebuchi M, et al. Re: Spontaneous rupture of renal
metastasis of hepatocellular carcinoma: management by
emergency transcatheter arterial embolization. Cardiovasc
Intervent Radiol 2001; 24: 143–144.
9. Fukushima M, Isoyama E, Sakaridani N, Sanematsu H,
Kadowaki H, Hirakawa S, et al. Renal metastasis originated
from liver cancer. Nippon Hinyokika Gakkai Zasshi 1996;
10. Hsu YB, Lee PH, Sheu JC, Chen DS, Hsu HC. Hepatocel-
lular carcinoma with metastasis to the kidney: report of a
case. J Formos Med Assoc 1994; 93: 713–714.
11. Ohkuma S, Ogasawara T, Kawamura H, Kashima K,
Takahashi T, Takino T, et al. Right renal metastasis in a
patient with hepatocellular carcinoma. Nippon Shokakibyo
Gakkai Zasshi 1978; 75: 746–751.
12. Yuki K, Hirohashi S, Sakamoto M, Kanai T, Shimosato Y.
Growth and spread of hepatocellular carcinoma. A review
of 240 consecutive autopsy cases. Cancer 1990; 66: 2174–
13. Hasegawa Y, Nakano S, Sobue T, Fujita M, Ishiguro S,
Sasaki Y, et al. Analysis of factors affecting uptake of Tc-
99m Sn-N-pyridoxyl-5-methyl tryptophan by hepatocellu-
lar carcinoma. Ann Nucl Med 1994; 8: 139–145.
14. Hasegawa Y, Nakano S, Hiyama T, Sobue T, Yoshida Y,
Sasaki Y, et al. Relationship of Uptake of Technetium-
99m(Sn)-N-Pyridoxyl-5-Methyltryptophan by Hepatocel-
lular Carcinoma to Prognosis. J Nucl Med 1991; 32: 228–
15. Watanabe Y, Sugimoto S, Kobori K, Katsuyama N, Zeniya
M, Kawakami K. Studies on the Clinical Usefulness of
99mTc-N- Pyridoxyl-5-Methyltryptophan as a Hepatobiliary
Agent. KAKU IGAKU (Jpn J Nucl Med) 1982; 19: 1589–
16. Kato-Azuma M. Tc-99m(Sn)-N-Pyridoxylaminates: A New
Series of Hepatobiliary Imaging Agents. J Nucl Med 1982;