Persistent Primary Cytomegalovirus Infection After Deceased Donor Kidney Transplant: Ganciclovir Susceptibility of Human Cytomegalovirus With UL97 D605E Mutation: A Case Report.

BACKGROUND: Cytomegalovirus (CMV) could cause rejection in immunocompromised patients during early post-renal transplant stage. The American Transplant Society guidelines recommend prophylactic therapy with ganciclovir (GCV) for 3 to 6 months to prevent CMV infections in adult renal transplant patients. However, there is no recommended CMV treatment regimen for pediatric patients. MAIN FINDINGS: We performed deceased donor kidney transplant from an anti-CMV antibody-positive donor to an anti-CMV antibody-negative 15-year-old female recipient with end-stage renal disease caused by bilateral renal hypoplasia. One month after transplant, increase in positive cells in the CMV antigenemia assay indicated a primary CMV infection in the patient, who immediately received GCV. She was switched to foscarnet after 4 months of anti-CMV therapy because of clinical GCV resistance. CMV was isolated from the peripheral blood mononuclear cells but neutralizing antibody was not detected. Isolated CMV was susceptible to GCV and foscarnet, although it carried the UL97 D605E mutation, assumed to be associated with GCV resistance. CONCLUSIONS: The primary CMV infection presented a phenotypic clinical drug resistance, but all recovered CMV isolates were drug-susceptible even if isolated after prolonged anti-CMV therapy, indicating that immune status was more important for recovery from primary CMV infection than anti-CMV therapy.

Positron emission tomography of 5-HT transporter sites in the baboon brain with [11C]McN5652.

[11C]McN5652 is a new radioligand specific for 5-hydroxytryptamine (5-HT; serotonin) transporters. In this study we used [11C]McN5652 to image the 5-HT transporter sites in baboon brain by positron emission tomography (PET). Dynamic PET studies were performed in three Papio anubis baboons. The animals were injected intravenously first with 11C-labeled (+)-McN5652([11C](+)McN5652), then with pharmacologically inactive enantiomer 11C-labeled (-)-McN5652 ([11C](-)McN5652); two animals received a third study with [11C](+)McN5652 after pretreatment with the specific 5-HT uptake site inhibitor fluoxetine (5 mg/kg). Initial uptake into the brain was similar for both [11C](+)McN5652 and [11C](-)McN5652. At later times (45-120 min after injection), only [11C](+)McN5652 showed a distribution characteristic for 5-HT uptake sites. In contrast, in studies with [11C](-)McN5652 and in those with [11C](+)McN5652 after 5-HT uptake site blockade with fluoxetine, 11C radioactivity concentrations were significantly lower and the distribution pattern was relatively even. The differences between [11C](+)-and (-)McN5652 were calculated for the time interval 95-125 min postinjection and used to estimate specific binding. Specific binding correlated well (r = 0.95, p < 0.001) with the known density of 5-HT uptake sites in human brain. These results indicate that [11C](+)McN5652 is suitable for PET imaging of 5-HT uptake sites in primate brain.

A PET radiotracer for studying serotonin uptake sites: carbon-11-McN-5652Z.

A radioligand for imaging central serotonin (5-hydroxytryptamine; 5-HT) uptake sites by positron emission tomography (PET) has yet to be developed. Such a tracer would be useful for the study of normal and altered serotonergic neurotransmission as well as for the detection of serotonergic neurotoxicity. This paper describes the labeling of the highly potent serotonin (5-HT) uptake blocker, McN-5652-Z (trans-1,2,3,5,6,10 beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline; racemic mixture), with 11C and the evaluation of this radiotracer in rodents with respect to its in vivo binding characteristics. In mouse brain, 11C-McN-5652-Z accumulated rapidly in regions with high densities of 5-HT uptake sites. The ratio between hypothalamus and cerebellum was 1.5:1 at 15 min and increased with time to 4.6:1 at 90 min after injection. The distribution of 11C-McN-5652 in rat brain at 60 min correlated well with regional concentrations of 5-HT uptake sites (r = 0.86). The specificity and selectivity of 11C-McN-5652 binding to the 5-HT transporter were tested by preinjecting blocking doses of known 5-HT, dopamine and norepinephrine uptake inhibitors, and a 5-HT2 receptor blocker before injection of the radiotracer. Preinjection of increasing doses of unlabeled McN-5652-Z inhibited 11C-McN-5652-Z binding in a dose-dependent fashion. These results suggest that the in vivo binding of the radiotracer was specific, selective for 5-HT uptake sites, saturable and that 11C-McN-5652-Z holds promise as a radiotracer for PET imaging of 5-HT uptake sites in the mammalian brain.

In vivo labeling of the dopamine D2 receptor with N-11C-methyl-benperidol.

A new dopamine D2 receptor radiotracer, N-11C-methyl-benperidol (11C-NMB), was prepared and its in vivo biologic behavior in mice and a baboon was studied. Carbon-11-NMB was determined to bind to specific sites characterized as dopamine D2 receptors. The binding was saturable, reversible, and stereospecific. Kinetic studies in the dopamine D2 receptor-rich striatum showed that 11C-NMB was retained five times longer than in receptor-devoid regions, resulting in a high maximum striatal-to-cerebellar ratio of 11:1 at 60 min after injection. From frontal cortex and cortex, on the other hand, the tracer washed out as rapidly as it did from cerebellum, resulting in tissue-to-cerebellar ratios close to one in these regions at any time after injection. Blocking studies confirmed the specificity and selectivity of the 11C-NMB binding to the dopamine D2 receptor. A PET study with 11C-NMB of the baboon brain revealed highly selective labeling of dopamine D2 receptor sites which was blocked by preinjection of raclopride.

Radiosynthesis and biodistribution of the S-[18F]fluoroethyl analog of McN5652.

[11C]McN5652 has been reported to exhibit favorable properties as a PET radiotracer for studying serotonin uptake sites. However, the use of this radiotracer may be limited by the short half-life of11C. To obtain a tracer with longer physical half-life, we have synthesized the S-[18F]fluoroethyl analog of McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([18F]fluoroethylthio)-phenyl] pyrrolo-[2,1-a]-isoquinoline) ([18F]FEMcN) and evaluated as a PET radiotracer for imaging serotonin uptake sites. The radiosynthesis was performed via a one-pot, two-step procedure. In the first step, 1-bromo-2-[18F]fluoroethane was prepared from 2-bromoethyl triflate and K18F/Kryptofix 2.2.2. in THF at room temperature. The second step, the S-fluoroalkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2-[18F]fluoroethane, by adding the normethyl McN5652 to the reaction vial, which was warmed at 45 degrees C for 1 min. The fluoroalkylation reaction proceeded quickly, giving [18F]FEMcN in an average overall radio-chemical yield of 13 +/- 7%. The specific activity was 1593 +/- 625 mCi/mumol. Ex vivo autoradiographic studies revealed that [18F]FEMcN accumulated into regions with high densities of 5-HT uptake sites such as hypothalamus, substantia nigra, and raphe nuclei. With blockade by nitroquipazine, a selective and highly potent 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, suggesting that this radiotracer binds specifically to 5-HT uptake sites. The regional distribution of [18F]FEMcN at 60 min postinjection correlated with the distribution of [11C]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT uptake blocker agreed with the distribution of the number of 5-HT uptake sites measured in vitro. Thus, 5-HT uptake sites were visualized in vivo with [18F]FEMcN. However, comparison with the in vivo behavior of [11C]McN5652 indicated less favorable properties of [18F]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood-brain barrier penetration and lower target-to-nontarget ratios.

An improved method for the synthesis of radiolabeled McN5652 via thioester precursors.

An improved procedure that facilitates routine production and increases the radiochemical yield of [11C]McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([11C]methylthio)-phenyl]pyrrolo- [2,1-alpha]-isoquinoline) is presented. Specifically, thiol acetate, butyrate, and benzoate derivatives of McN5652 were prepared as the precursors for the [11C]McN5652 synthesis. These thioesters offer greater stability than the previously used thiol precursor (desmethyl McN5652) and enable a single batch of material to be used for multiple radiolabelings. Hydrolysis of the thioester functionality (tetrabutylammonium hydroxide, 10 min) unmasked the free thiol which, without purification, was reacted with [11C]iodomethane in DMF at 40-45 degrees C for 1 min. The average decay-corrected radiochemical yield for [11C]McN5652 was 26% with an average specific activity of 2290 mCi/mumol (end of synthesis). This facile radiolabeling method, utilizing the butyrate thioester of McN5652, was also employed in the preparation of [3H](+)- and (-)McN5652 [trans-1,2,3,5,6S (or 6R),10bR, (or 10bS)-hexahydro-6-[4-([3H]methylthio)phenyl]pyrrolo-[2,1,alpha]- isoquinoline] from [3H]iodomethane.

Highly potent indanamine serotonin uptake blockers as radiotracers for imaging serotonin uptake sites.

Two highly potent indanamine serotonin (5-HT) uptake blockers, trans-3'-(4'-bromophenyl)-1-indanamine (trans-[11C]DBPI or [11C]Lu 19-056) and its iodo analog, trans-3'(4'-[125I]iodophenyl)-1-indanamine (trans-[125I]DIPI) were evaluated as radiotracers for imaging 5-HT uptake sites in vivo Trans-[11C]DBPI was synthesized by N-methylation of the normethyl precursor with [11C]iodomethane. Trans-[125I]DIPI was synthesized by iododestannylation of the tributyltin precursor with [125I]NaI. Radiochemical yields for the [11C] and [125I] radiotracers were 34 and 40% with specific activities of 4000 and 1800 mCi/mumol, respectively. In vitro, the iodo analog, trans-DIPI, showed an IC50 value of 0.26 nM in inhibition of [3H]paroxetine binding to 5-HT uptake sites in rat cortex. The potency was found to be equivalent to that of paroxetine or McN5652. In vivo, after i.v. injection into mice, both radiotracers showed high uptake in brain (3-4% dose/whole brain at 15 min) and high accumulation into target tissues such as hypothalamus and olfactory tubercles (7-8% dose/g at 60 min). The binding was blocked by pre-injection of 5 mg/kg of peroxetine. While the in vivo distribution agreed with previously reported 5-HT uptake site distribution, the radiotracers showed high uptake in non-target tissues such as cerebellum, resulting in low target-to-non-target ratios (1.5-1.6 at 60 min). Since washout from non-target regions was slower than from target regions, longer-time observation with 125I up to 6 h did not improve the ratios. HPLC analyses of mouse brain homogenates and blocking studies indicated that the high uptake in non-target regions is not the result of metabolism or any interaction of the radiotracers with those tissues via specific binding sites. In spite of low target-to-non-target ratios, target regions with high density of 5-HT uptake sites, such as the raphe nuclei, superior colliculi and substantia nigra, were visualized with trans-[125I]DIPI by ex vivo autoradiography, since the radiotracer showed high specific binding (total mimus nonspecific binding).

[11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET.

The in vivo behavior of the stereoisomers of [11C]McN5652, a highly potent serotonin (5-HT) uptake blocker, was determined to evaluate their utility as radiotracers for imaging 5-HT uptake sites by positron emission tomography (PET). After intravenous injection into mice, [11C](+)McN5652 showed markedly higher uptake and longer retention in regions with high density of 5-HT uptake sites than the [11C]-labeled racemic mixture, while [11C](-)McN5652 washed out rapidly. With the [11C](+)-enantiomer, the ratio between hypothalamus and cerebellum reached 6 at 90 minutes. The binding of [11C](+)McN5652 was inhibited by 45-73% by pre-injection of 5 mg/kg of paroxetine, a selective 5-HT uptake blocker, in all regions examined except cerebellum where no significant effect of the drug was observed. [11C](-)McN5652 showed no specific binding in any of the regions. The [11C]-labeled cis isomer, [11C]McN5655, revealed surprisingly low brain penetration and showed no significantly higher uptake in regions of interest than cerebellum. These results suggest that [11C](+)McN5652 is a promising candidate as a PET radiotracer for studying 5-HT uptake sites in vivo.

In vivo biodistribution of a radiotracer for imaging serotonin-1A receptor sites with PET:[11C]LY274601.

LY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mg/kg, s.c.), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocampus CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2-2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.

Analyses of serum lipoprotein(a) and the relation to phenotypes and genotypes of apolipoprotein(a) in type 2 diabetic patients with retinopathy.

To elucidate the association of lipoprotein(a) (Lp(a)) with diabetic retinopathy (DR), we studied the serum Lp(a) concentrations (n = 412), apolipoprotein(a) (apo(a)) phenotypes expressed by the number of kringle 4 (K4) repeats (n = 150), apo(a) gene genotypes (n = 161) of type 2 diabetes with or without DR. The 5'-untranslated region of apo(a) gene was classified into seven haplotypes (A to G) and 18 genotypes by PCR-RFLP at three distinct sites. The serum Lp(a) concentrations were significantly higher in diabetic patients than in normal controls. Furthermore, the patients with DR, especially proliferative retinopathy showed higher serum Lp(a) concentrations than those without DR. Although a negative correlation was found between the serum Lp(a) concentrations and the number of K4 repeats in total diabetic patients, no difference was seen in the distribution of the number of K4 repeats between those with and without DR. In the same apo(a) phenotypes, the patients with DR had higher Lp(a) concentrations than those without DR. Among the genotypes, type CC showed significantly higher serum Lp(a) concentrations than the other genotypes. However, there was no difference in the ratios of the type CC between the patients with and without DR. In conclusion, other factors than phenotypes and genotypes in the 5'-untranslated region of apo(a) may be responsible for the elevation of serum Lp(a) in diabetic patients with retinopathy.

Abnormal 13C-fatty acid breath tests in patients treated with valproic acid.

Breath tests using fatty acids labeled with a stable isotope (carbon 13) were carried out on epileptic patients treated with valproic acid in order to detect abnormal fatty acid metabolism. The patients were given 13C-octanoic acid or 13C-palmitic acid orally, and expired air was collected at appropriate intervals for the analysis of 13CO2 content by a mass spectrometer. Eight patients were tested in the palmitic acid breath test and nine patients in the octanoic acid breath test. Controls for these tests were patients treated with antiepileptic drugs other than valproic acid and unmedicated cerebral palsy patients. In the valproic acid-treated group, 13C recovery was reduced by 56% in seven hours on the 13C-palmitic acid breath test, while the octanoic acid breath test showed a 52% reduction in one hour. This suppression of fatty acid oxidation was significantly correlated with dose of valproic acid in both tests. No influence of other drugs was detected, and the effect of administered carnitine was not conclusive. This study demonstrates the usefulness of 13C-labeled fatty acid breath tests in clinical practice.

Occurrence of Graves' disease during retreatment with interferon-alpha 2a for chronic hepatitis C.

The present report describes a patient who developed Graves' disease 3 months after inception of retreatment with higher doses of interferon-alpha 2a for chronic hepatitis C, although the initial 6-month treatment caused no serious adverse reactions. Severe hyperthyroidism continued despite discontinuation of interferon-alpha 2a, and the patient was subsequently treated with 131I. This case suggests careful evaluation of the safety of retreatment to prevent manifestation of such a complication in the retreatment of chronic hepatitis C with interferon.

Localization of hyperfunctioning parathyroid glands by means of thallium-201 and iodine-131 subtraction scintigraphy in patients with primary and secondary hyperparathyroidism.

The accuracy of the preoperative localization of hyperfunctioning parathyroid glands by subtraction scintigraphy with 201Tl and 131I was evaluated by comparison with the operative findings. The subjects were 67 consecutive patients with hyperparathyroidism (HPT), including 24 with primary and 43 with secondary HPT. In primary HPT, surgery revealed 26 adenomas weighing 0.26-15.80 g (mean +/- SD; 3.01 +/- 3.04 g). Two patients had double adenomas. Scintigraphy correctly localized 25/26 adenomas (96.2%) in primary HPT for a sensitivity, specificity, and accuracy of 96.2%, 98.5%, and 97.9%, respectively. In secondary HPT, 163 hyperplastic glands weighing 0.03-5.08 g (0.85 +/- 0.93 g) were found. Scintigraphy correctly localized 79 glands (48.5%) weighing 0.03-5.08 g (1.19 +/- 1.10 g), but 84 glands (51.5%) weighing 0.04-2.70 g (0.51 +/- 0.50 g) were not detected. Thus, the sensitivity, specificity, and accuracy of scintigraphy were respectively 48.5%, 100%, and 51.2%, in secondary HPT. These results show that scintigraphy with 201Tl and 131I can be used to locate abnormal parathyroid glands with an efficacy equal to or better than that of the conventional methods with 201Tl and 99mTc or 201Tl and 123I.

Circulating forms of immunoreactive parathyroid hormone-related protein for identifying patients with humoral hypercalcemia of malignancy: a comparative study with C-terminal(109-141)- and N-terminal(1-86)-region-specific PTHrP radioassay.

We evaluated the circulating forms of immunoreactive PTHrP in 115 healthy subjects and 122 patients with malignant diseases by using radioassay systems (RAS) specific for the C-terminal (109-141) fragment of PTHrP (C-RAS) and for the N-terminal(1-86) (N-RAS). PTHrP levels in healthy controls ranged from 1.5 to 38.2 (mean: 24.5) pmol/L with the C-RAS and from 0.9 to 2.5 (mean: 1.7) pmol/L with the N-RAS. The ratio of circulating N-terminal fragment (N) to C-terminal fragment (C) of PTHrP was calculated to be about 1: 14.4 in the healthy subjects. Of the 122 patients with malignant diseases, 40 (32.8%) had circulating PTHrP levels undetectable with the N-RAS, but only 11 (9.0%) patients had levels undetectable with the C-RAS. Of the former 122 patients, 41 (33.6%) had high PTHrP as determined with the C-RAS, and 10 (8.2%) had high PTHrP as determined with the N-RAS. The former of these included only 8 (19.5%) HHM patients, while the latter included 8 (80.0%) HHM patients. The circulating N to C ratio was about 1: 70.7 in the HHM patients. The N and C obtained with the different RASs showed a close correlation (r = 0.86). The values also showed a close correlation with serum Ca; r = 0.75 for C-RAS and r = 0.81 for N-RAS. In addition, the correlations between the PTHrP reading obtained with the different RASs and serum Cr were: r = 0.42 with C-RAS and r = 0.26 with N-RAS. The circulating form of immunoreactive PTHrP fragments is therefore comprised mainly of PTHrP(109-141). In contrast, circulating concentrations of the PTHrP(1-86) fragment are very low, but detection of the PTHrP(1-86) fragment with the N-RAS is a more useful indicator of HHM with fewer false positive results and is less likely to be influenced by renal function than the detection of the PTHrP(109-141) fragment with C-RAS.

Detection of bile leakage into the thoracic cavity by hepatobiliary scintigraphy.

We report early detection of bile leakage into the thoracic cavity by hepatobiliary scintigraphy in a rare case of spontaneous withdrawal of the catheter for percutaneous transhepatic cholangiographic drainage (PTCD). An 81-year-old man with inoperable carcinoma of the common bile duct was readmitted with a 38 degrees C fever and suspected bile leakage from the hepatic biliary tree following withdrawal of the catheter for PTCD. While plain X-ray immediately after readmission revealed no abnormality in the chest or abdomen, hepatobiliary scintigraphy revealed not only bile leakage into the right thoracic cavity but also the site of laceration. We conclude that hepatobiliary scintigraphy is a simple, non-invasive procedure useful in the early detection and localization of bile leakage following spontaneous withdrawal of the catheter for PTCD.

Thyroid imaging in a typical case of acute suppurative thyroiditis with abscess formation due to infection from a persistent thyroglossal duct.

The clinical evaluation of thyroid imaging with 99mTc, 201Tl, and 67Ga in the uncommon, but potentially serious, disorder of acute suppurative thyroiditis (AST) with abscess formation due to infection from a persistent thyroglossal duct is reported. The 99mTc image showed functioning areas of the diseased thyroid gland and the 201Tl image demonstrated abscess formation in the thyroid gland of this patient. In addition, marked 67Ga accumulation was demonstrated in a wide area covering not only the area of the thyroid gland involved, but also associated circumferential inflammatory lesions in a patient with AST. The net thyroid uptake of 67Ga at 72 hours was calculated to be 13.8% of the injected dose.

Myocardial uptake of antimyosin antibody compared with serum myosin light chain I levels in patients with myocardial infarction.

Myocardial accumulation of In-111-antimyosin (InAM) was evaluated in comparison with circulating serum myosin light chain I (LCI) level at the time of InAM injection. Seventeen consecutive patients were studied at various stages ranging from 6 days to 34 days after myocardial infarction (MI). The infarct area was positive for InAM uptake in all patients (100%), and significant myocardial uptake was observed in 14 patients (82.4%). The intensity of InAM uptake correlated with the infarct location shown by ECG and CAG. In contrast, 12 patients (70.6%) had normal or undetectable serum myosin LCI levels, with 5 being normal (0.42-2.5 ng/ml) and 7 undetectable (0.42 ng/ml or less). Only 5 patients (29.4%) had elevated serum myosin LCI levels at the time of InAM injection, and this elevation was slight, ranging from 3.4 to 4.5 ng/ml (mean: 3.75 ng/ml). Among patients with undetectable, normal, and elevated serum myosin LCI levels, there was no significant correlation between InAM uptake and the serum myosin LCI level. Thus, even after the serum myosin LCI level has decreased to normal, InAM can still bind to cardiac myosin in patients with MI, presumably until there is complete recovery from the hibernating myocardium due to ischemic damage.

Plummer's disease with spontaneous progression to hypothyroidism.

A case of Plummer's disease that spontaneously progressed to hypothyroidism is presented. A 49-year-old female visited our hospital because of a 3 kg decrease in body weight during the previous month and a painless nodule in the right anterior area of her neck. A diagnosis of Plummer's disease was made based on the results of thyroid function tests, thyroid scintigrams, and an ultrasonogram, but the patient's disease followed an usual clinical course. About two months later, she gradually developed manifestations of permanent hypothyroidism, and anti-thyroid autoantibodies became positive. In spite of continuous administration of levothyroxine sodium, uptake of 99mTcO4- to the nodule was unchanged or rather increased according to the consecutive thyroid scintigraphies. These results suggested that this case represented an autonomously functioning nodule with underlying silent thyroiditis and Hashimoto's disease.

Serum thymidine kinase, a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase.

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.